EP2892561A1 - Hiv vaccine compositions and methods - Google Patents

Abstract

Embodiments relate methods and composition involving an HIV vaccine comprising an anti-LOX-1 antibody or a fragment thereof to which at least one HIV antigen is attached to form an antibody-antigen fusion protein (Ab.Ag) or an antibody-antigen complex (Ab:Ag). Embodiments also concern methods and compositions involving a combined HIV vaccine comprising a first HIV vaccine according as described above and a second HIV vaccine.

Description

DESCRIPTION

HIV VACCINE COMPOSITIONS AND METHODS

BACKGROUND OF THE INVENTION

[0001] This application claims priority to U.S. Provisional Patent Applications Serial No. 61/698,432 filed on September 7, 2012, the contents of which are incorporated herein by reference in their entirety.

1. Field of the Invention

[0002] The present invention relates generally to the field of prophylactic and therapeutic vaccines against an HIV infection. More specifically, the invention relates to a HIV vaccine comprising an anti-LOX-1 antibody or a fragment thereof to which at least one HIV antigen is fused or conjugated and combined HIV vaccines comprising the vaccine as described therein.

2. Description of Related Art

[0003] While treatment for HIV/AIDS has become a reality, in the United States an average of 50,000 new HIV infections are diagnosed each year in the United States and there is an estimated 34 million people living with HIV worldwide.

[0004] While a variety of options have been explored, dendritic cells (DCs) are antigen-presenting cells that play a key role in regulating antigen-specific immunity (Mellman and Steinman 2001), (Banchereau, Briere et al. 2000), (Cella, Sallusto et al. 1997). DCs capture antigens, process them into peptides, and present these to T cells. Therefore delivering antigens directly to DC is a focus area for improving vaccines. One such example is the development of DC-based vaccines using ex-vivo antigen-loading of autologous DCs that are then re-administrated to patients (Banchereau, Schuler-Thurner et al. 2001), (Steinman and Dhodapkar 2001). [0005] Another strategy to improve vaccine efficacy is specific targeting to DC of antigen conjugated to antibodies against internalizing DC-specific receptors. With the continued epidemic of AIDS throughout the world, there is still a need for HIV vaccines and treatment methods. SUMMARY OF THE INVENTION

[0006] Methods and compositions are provided that can be used to vaccinate against and treat HIV. Specifically contemplated are vaccine compositions and methods of administering these compositions to patients. Embodiments are focused on an HIV antigen that is attached, fused, coupled to, or conjugated to a dendritic cell targeting agent such that the HIV antigen is provided to the dendritic cell via the targeting agent such as through receptor-mediated endocytosis.

[0007] In particular embodiments, the dendritic cell targeting agent is an antibody that recognizes a receptor on a dendritic cell. In some cases, the antibody specifically recognizes LOX-1, CD40, DCIR, CDIA, DC-SIGN, DC-SIGN/L, CLEC-6, DC-ASGPR, LANGERIN, or DECTIN-1. It is also contemplated that the dendritic cell targeting agent may be a compound that binds to a dendritic cell receptor and that promotes receptor-mediated endocytosis. The antibody may be all or part of an antibody, such as an antibody fragment, or it may be an antibody that has been modified. In certain embodiments, the antibody has a variable region for the light and/or heavy chains of an antibody that recognizes LOX-1, CD40, DCIR, CDIA, DC-SIGN, DC-SIGN/L, CLEC-6, DC-ASGPR, LANGERIN, or DECTIN-1. In further embodiments, the antibody is a monoclonal antibody. A monoclonal antibody may be from a mouse, rat, rabbit, human or other mammal. In cases where the antibody is not a human antibody, the antibody may be humanized. [0008] Some compositions and methods involve an HIV vaccine comprising an anti-

LOX-1 antibody, or a fragment thereof, attached to at least one HIV antigen. In some embodiments, the antibody or antibody fragment may be fused to form an antibody-antigen fusion protein (Ab.Ag). In other embodiments, the antibody or antibody fragment might be conjugated to at least one HIV antigen to form an antibody-antigen complex (Ab:Ag). In certain embodiments the HIV antigen is an envelope protein from HIV.

[0009] In one embodiment, the anti-LOX-1 antibody is a recombinant monoclonal antibody. In another embodiment, the anti-LOX-1 antibody is a humanized antibody. In yet another embodiment, the antibody fragment is selected from the group consisting of an Fv, Fab, Fab', F(ab')2, Fc, or a ScFv fragment. In certain aspects the anti-LOX-1 antibody is expressed by a hybridoma selected from clones 9D7-10-4, 8B4-10-2, 1 1 C8-B7, 13B1 1-A8 and 15C4. In other embodiments, the antibody has an amino acid sequence that is, is at least or is at most 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, 99, or 100% identical to the sequence of any variable region or heavy or light chain provided herein. In certain embodiments, an antibody comprises 1 , 2, 3, 4, 5, or 6 CDRs of a variable region provided herein. In further embodiments, an antibody comprises one or more regions that are 80, 85, 90, 95, 96, 97, 98, 99, or 100% identical to 1 , 2, 3, 4, 5, or 6 CDRs of a variable region provided herein.

[0010] In some embodiments, there is an anti-LOX-1 antibody comprising an amino acid sequence that is, is at least or is at most 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, 99, or 100% identical to the amino acid sequence of VH1, VH2, VH3, VH4, VH5, VH6, and/or VH7 disclosed herein, which correspond to SEQ ID NOs:73, 75, 77, 79, 81 , 83, and 85, respectively. In additional embodiments, there is an anti-LOX-1 antibody comprising an amino acid sequence that is, is at least or is at most 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, 99, or 100% identical to the amino acid sequence of VK1, VK2, and/or VK3 disclosed herein, which correspond to SEQ ID NOs: 87, 89, and 91, respectively. It is specifically contemplated that CDR1 , CDR2, and/or CDR3 (denoted by underline formatting in nucleotide and amino acid sequences) from any of VTIl , VH2, VH3, VH4, VH5, VH6, VH7, VK1, VK2, and/or VK3 may be included in any anti-Lox-1 antibody. Moreover, nucleic acid constructs encoding of the amino acids sequences is contemplated for use in various embodiments. Such a nucleic acid construct may be expressed in a host cell to produce the encoded antibody.

[0011] In one embodiment, the fusion protein comprises at least one peptide linker (PL) between the anti-LOX-1 antibody or fragment thereof and the HIV antigen.

[0012] In one particular embodiment, the antibody-antigen fusion protein (Ab.Ag) comprises the following formula: Ab-(PL-Ag)x;

Ab-(Ag-PL)x;

Ab-(PL-Ag-PL)x;

Ab-(Ag-PL-Ag)x;

Ab-(PL-Ag)x-PL; or Ab-(Ag-PL)x-Ag; wherein Ab is an anti-LOX-1 antibody or a fragment thereof; wherein PL is a peptide linker; wherein Ag is a HIV antigen; and, wherein x is an integer from 1 to 20, or any range derivable therein. [0013] In a particular embodiment, the PL comprises an alanine and a serine. In another embodiment, the PL further comprises a flexible linker. In some cases, flexible linker sequences are derived from Scaffoldins and related proteins. In one embodiment, the flexible linker is QTPTNTISVTPTNNSTPTNNSNPKPNP (SEQ ID NO : 1). In another embodiment, the flexible linker is QTPTNTISVTPTNNSTPTNTSTPKPNP (SEQ ID NO :2). In certain embodiments, two PL comprising an alanine and a serine are separated by the flexible linker. In another embodiment, the flexible linker comprises one or more glycosylation sites that provide increased flexibility between the antibody and the antigen, decreased proteolysis at the linker and increased secretion.

[0014] In one embodiment, the -(PL-Ag)x, -(Ag-PL)x, -(PL-Ag-PL)x, or -(Ag-PL- Ag)x are located at the carboxy terminus of the Ab heavy chain or fragment thereof.

[0015] In another embodiment, the -(PL-Ag)x, -(Ag-PL)x, -(PL-Ag-PL)x, or -(Ag- PL-Ag)x are located at the carboxy terminus of the Ab light chain or fragment thereof.

[0016] As demonstrated in the section Examples below, engineered recombinant anti- LOX-1 recombinant antibody- antigen fusion proteins are efficient vaccines in vivo in NHP. [0017] Expression vectors may be constructed with diverse protein coding sequence e.g., fused in-frame to the H chain coding sequence. For example, HIV antigens such as HIV Env antigen may be expressed subsequently as Ab.Ag, which in the context of this invention, can have utility derived from using the anti-LOX-1 V-region sequence to bring the antigen directly to the surface of the antigen presenting cell bearing LOX-1. This permits internalization of e.g., antigen and ensuing initiation of therapeutic or protective action (e.g., via initiation of a potent immune response).

[0018] In some cases, particular amino acid sequences corresponding to anti-LOX-1 monoclonal antibodies that are desirable components (in the context of e.g., humanized recombinant antibodies) of therapeutic or protective products. The following are such sequences in the context of chimeric mouse V region (underlined) human C region recombinant antibodies. These mouse V regions can be readily humanized, i.e., the LOX-1 combining regions grafted onto human V region framework sequences, by anyone well practiced in this art. Furthermore, the sequences can also be expressed in the context of fusion proteins that preserve antibody functionality, but add e.g., antigen for desired therapeutic applications.

[0019] Vaccine compositions may also contain one or more adjuvants. The adjuvants may be attached or conjugated directly or indirectly to one or more of the vaccine components, such as an antigen or antibody. In other embodiments the adjuvants may be provided or administered separately from the vaccine composition. In certain embodiments the adjuvant is poly ICLC, CpG, LPS, Immunoquid, PLA, GLA or cytokine adjuvants such as IFNa. In other embodiments the adjuvant may be a toll-like receptor agonist (TLR). Examples of TLR agonists that may be used comprise TLR1 agonist, TLR2 agonist, TLR3 agonist, TLR4 agonist, TLR5 agonist, TLR6 agonist, TLR7 agonist, TLR8 agonist or TLR9 agonist. In certain embodiments, a vaccine composition specifically does not contain PLA as an adjuvant.

[0020] Thus, an exemplary prototype HIV vaccine based on this concept could use a H chain vector such as C2272 [hAnti-LOX-1 VH3-LV-hIgG4H-C-Flex-vl-ViralenvHIV- g l 40-C-6xHis] (SEQ ID NO: 7) which directs the synthesis of a H chain human mAb V region-human IgG4 C region-gpl 40 fusion protein. Co-expressed with the analogous light chain expression plasmid (C2266), this produces a multifunctional recombinant antibody (rAb) that binds LOX-1 and delivers Env antigen to the cell surface for DC activation, antigen internalization, antigen processing, antigen presentation, and education and expansion of specific anti-Env B and T cells. [0021] Alternatively, the anti-LOX-1 antibody or fragment is bound or fused to one half of a Cohesin/Dockerin pair and the HIV antigen is bound or fused to the complementary half of the Cohesin/Dockerin pair to form said antibody-antigen complex (Ab:Ag).

[0022] In some embodiments, an HIV vaccine composition comprises a dendritic cell targeting complex comprising an anti-CD40 antibody, or a fragment thereof, attached to at least one HIV antigen. In some instances, the HIV vaccine composition comprises an anti- CD40 antibody and antigen attached through a peptide linker (PL). [0023] In specific embodiments, an HIV vaccine composition includes a dendritic cell targeting complex comprising one or more of the following formulas:

Ab-(PL-Ag)x;

Ab-(Ag-PL)x;

Ab-(PL-Ag-PL)x;

Ab-(Ag-PL-Ag)x;

Ab-(PL-Ag)x-PL; or

Ab-(Ag-PL)x-Ag;

wherein Ab is an anti-CD40 antibody or a fragment thereof; wherein PL is a peptide linker; wherein Ag is a HIV antigen; and wherein x is an integer from 1 to 20. In certain embodiemtns the PL comprises an alanine and a serine. In additional embodiments the PL further comprises a flexible linker, which can in certain instances comprise one or more glycosylation sites. Specifically, the flexible linker may be QTPTNTISVTPTN STPTN SNPKPNP (SEQ ID NO: 1). In some embodiments, the -(PL- Ag)x, -(Ag-PL)x, -(PL-Ag-PL)x, or -(Ag-PL-Ag)x modules are located at the carboxy terminus of the Ab heavy chain or fragment thereof.

[0024] In some embodiments, the anti-CD40 antibody or fragment is bound or fused to one half of a Cohesin Dockerin pair and at least one HIV antigen is bound or fused to the complementary half of the Cohesin/Dockerin pair to form an antibody-antigen complex (Ab:Ag). In specific embodiments the antibody-antigen complex (Ab:Ag) comprises the one or more of the following formulas:

Ab.Doc:Coh.Ag;

Ab.Coh:Doc.Ag;

Ab.(Coh)x:(Doc.Ag)x;

Ab.(Doc)x:(Coh.Ag)x;

Ab.(Coh.Doc)x:(Doc.Ag^!)(Coh.Ag²); or

Ab.(Coh)x(Doc)x:(Doc.Ag¹)x(Coh.Ag²)x; wherein Ab is an anti-CD40 antibody or a fragment thereof; wherein Ag is a HIV antigen (Ag' and Ag² being two distinct HIV antigens); wherein Doc is Dockerin; wherein Coh is Cohesin and wherein x is an integer from 1 to 10.

[0025] In certain instances an HIV antigen elicits at least one of a humoral or a cellular immune response in a host. The HIV antigen can be selected from the group consisting of HIV Gag, Pol, Pro, Tat, Nef, Rev, Vif, Vpr or Env antigens. Specifically, an Env antigen can be selected form the group consisting of gp41, gpl20, gpl40 and gpl 40 with a C-terminal deletion. Additionally, an HIV vaccine can further comprise an adjuvant. Specifically, the adjuvant can be conjugated to an anti-CD40 antibody or fragment thereof and/or to at least one HIV antigen. The adjuvant may be selected from Poly ICLC, Immunoquid, CPG, GLA or TLR any agonists.

[0026] In some embodiments, an HIV vaccine comprises a population of dendritic cells (DC) activated with an antibody-antigen fusion protein (Ab.Ag) or an antibody-antigen complex (Ab:Ag) as described for anti-CD40 vaccines. In yet other embodiments a first anti- CD40 HIV vaccine is combined with a second HIV vaccine. The second HIV vaccine may be selected from the group consisting of an attenuated recombinant virus, a naked DNA vaccine and a DC-targeting vaccine. In certain embodiments, the attenuated recombinant virus may be an attenuated recombinant poxvirus.

[0027] In other embodiments, the attenuated recombinant poxvirus is selected from the group consisting of NY VAC, ALVAC and MVA virus. Specifically, the NYVAC virus may be a NYVAC-KC virus..

[0028] In some instances the second vaccine is a separate or different DC-targeting vaccine comprising an anti-DC receptor antibody or a fragment thereof to which at least one HIV antigen is fused or conjugated to form an antibody-antigen fusion protein (Ab.Ag) or an antibody-antigen complex (Ab:Ag).

[0029] In some embodiments, the anti-CD40 vaccine is used in a method for potentiating an immune response to at least one HIV epitope comprising administering to a patient an anti-CD40 HIV vaccine. In other embodiments, the anti-CD40 vaccine is used in a method of treating a patient in the early stages of an HIV infection comprising administering to a patient an anti-CD40 HIV vaccine. In some embodiments, the anti-CD40 HIV vaccine comprises an antibody-antigen fusion protein (Ab.Ag) comprising a peptide linker (PL) between said anti-CD40 antibody or fragment thereof and at least one HIV antigen. Specifically, the antibody-antigen fusion protein (Ab.Ag) can comprises the one ore more of the following formulas:

Ab-(PL-Ag)x;

Ab-(Ag-PL)x;

Ab-(PL-Ag-PL)x;

Ab-(Ag-PL-Ag)x;

Ab-(PL-Ag)x-PL; or

Ab-(Ag-PL)x-Ag;

wherein Ab is an anti-CD40 antibody or a fragment thereof; wherein PL is a peptide linker; wherein Ag is a HIV antigen; and wherein x is an integer from 1 to 20. PL can comprise an alanine and a serine, a flexible linker or a flexible linker that includes one or more glycosylation sites. Specifically, the flexible linker can be QTPTNTISVTPTNNSTPTN SNPKPNP (SEQ ID NO: 1). In other embodiments, the molecules corresponding to the portion of the formula described by -(PL-Ag)x, -(Ag-PL)x, - (PL-Ag-PL)x, or -(Ag-PL-Ag)x are located at the carboxy terminus of the Ab heavy chain or fragment thereof. In some instances, the anti-CD40 antibody or fragment is bound or fused to one half of a Cohesin/Dockerin pair and at least one HIV antigen is bound or fused to the complementary half of the Cohesin/Dockerin pair to form an antibody-antigen complex (Ab:Ag). In certain embodiments, the antibody-antigen complex (Ab:Ag) comprises one or more of the following formulas:

Ab.Doc:Coh.Ag;

Ab.Coh:Doc.Ag;

Ab.(Coh)x:(Doc.Ag)x;

Ab.(Doc)x:(Coh.Ag)x;

Ab.(Coh.Doc)x:(Doc.Ag')(Coh.Ag²); or

Ab.(Coh)x(Doc)x:(Doc.Ag')x(Coh.Ag²)x;

wherein Ab is an anti-CD40 antibody or a fragment thereof; wherein Ag is a HIV antigen (Ag¹ and Ag² being two distinct HIV antigens); wherein Doc is Dockerin; wherein Coh is Cohesin and wherein x is an integer from 1 to 10. In some embodiments, the HIV antigen is selected from the group consisting of HIV Gag, Pol, Pro, Tat, Nef, Rev, Vif, Vpr or Env antigens. In yet other embodiments the an Env antigen is gp41 , gpl 20, gpl40 or gpl40 with a C-terminal deletion. In other embodiments still, the HIV vaccine comprises an adjuvant. In specific embodiments, the adjuvant is conjugated to an anti-CD40 antibody or fragment thereof and/or to said at least one HIV antigen.

[0030] In one embodiment, the anti-CD40 antibody is a recombinant monoclonal antibody. In another embodiment, the anti-CD40 antibody is a humanized antibody. In yet another embodiment, the antibody fragment is selected from the group consisting of an Fv, Fab, Fab', F(ab')2, Fc, or a ScFv fragment. In certain aspects the anti-CD40 antibody is expressed by a hybridoma selected from clones 12E12 (variable heavy and light chains comprised by SEQ ID NOs : 123 and 124, respectively). In other embodiments, the antibody has an amino acid sequence that is, is at least or is at most 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, 99, or 100% identical to the sequence of any variable region or heavy or light chain provided herein. In certain embodiments, an antibody comprises 1 , 2, 3, 4, 5, or 6 CDRs of a variable region provided herein. In further embodiments, an antibody comprises one or more regions that are 80, 85, 90, 95, 96, 97, 98, 99, or 100% identical to 1 , 2, 3, 4, 5, or 6 CDRs of a variable region provided herein.

[0031] In some embodiments, there is an anti-CD40 antibody comprising an amino acid sequence that is, is at least or is at most 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, 99, or 100% identical to the amino acid sequence of VH1, VH2, VH3, and/or VH4 disclosed herein, which correspond to SEQ ID NOs: 93, 95, 97, and 99, respectively. In additional embodiments, there is an anti-CD40 antibody comprising an amino acid sequence that is, is at least or is at most 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, 99, or 100% identical to the amino acid sequence of VK1 , VK2, and/or VK3 disclosed herein, which correspond to SEQ ID NOs: 101 , 103, and 105, respectively. It is specifically contemplated that CDR1 , CDR2, and/or CDR3 (denoted by underline formatting in nucleotide and amino acid sequences) from any of VH1 , VH2, VH3, VH4, VK1 , VK2, and/or VK3 may be included in any anti-CD40 antibody. Moreover, nucleic acid constructs encoding of the amino acids sequences is contemplated for use in various embodiments. Such a nucleic acid construct may be expressed in a host cell to produce the encoded antibody. [0032] Non limiting examples of sources for the cohesin-dockerin binding pair include Clostridium thermocellum, Clostridium josui, Clostridium cellulolyticum and Bacteroides cellulosolvens and combinations thereof.

[0033] In one embodiment, the antibody-antigen complex (Ab:Ag) comprises the following formula

Ab.Doc:Coh.Ag;

Ab.Coh:Doc.Ag;

Ab.(Coh)x:(Doc.Ag)x;

Ab.(Doc)x:(Coh.Ag)x; Ab.CCoh.DocMDoc.Ag'XCoh.Ag²); or

Ab.(Coh)x(Doc)x:(Doc.Ag')x(Coh.Ag²)x; wherein Ab is an anti-LOX-1 antibody or a fragment thereof; wherein Ag is a HIV antigen (Ag¹ and Ag² being two distinct HIV antigens); wherein Doc is Dockerin; wherein Coh is Cohesin and wherein x is an integer from 1 to 10, or any range derivable therein. [0034] It is contemplated that at least one HIV antigen elicits at least one of a humoral and/or a cellular immune response in a host, preferably a human patient.

[0035] In one embodiment, the HIV antigen is selected from the group consisting of HIV Gag, Pol, Pro, Tat, Nef, Rev, Vif, Vpr or Env antigens. In yet another particular embodiment, the HIV Env antigen is selected from the group consisting of gp41 , gpl20, gpl40 and gpl40 with a C-terminal deletion.

[0036] In a second aspect, methods concern an HIV vaccine comprising a population of dendritic cells (DC) activated with an antibody-antigen fusion protein (Ab.Ag) or an antibody-antigen complex (Ab:Ag) as above-described.

[0037] In a certain aspect, to obtain said population of activated dendritic cells (DC), the followings steps are carried out: (a) isolating patient dendritic cells; (b) exposing the dendritic cells to activating amounts an antibody-antigen fusion protein (Ab.Ag) or an antibody-antigen complex (Ab:Ag); and (c) reintroducing the antigen-loaded, activated dendritic cells into the patient.

[0038] The preparation of HIV vaccine as the active immunogenic ingredient, may be prepared as injectables, either as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid prior to infection can also be prepared. The preparation may be emulsified, encapsulated in liposomes. The active immunogenic ingredients are often mixed with carriers which are pharmaceutically acceptable and compatible with the active ingredient.

[0039] The term "pharmaceutically acceptable carrier" refers to a carrier that does not cause an allergic reaction or other untoward effect in subjects to whom it is administered. Suitable pharmaceutically acceptable carriers include, for example, one or more of water, saline, phosphate buffered saline, dextrose, glycerol, ethanol, or the like and combinations thereof. In addition, if desired, the vaccine can contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, and/or adjuvants which enhance the effectiveness of the vaccine. Examples of adjuvants that may be effective include but are not limited to: aluminum hydroxide, N-acetyl-muramyl-L-threonyl-D-isoglutamine (thr- MDP), N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine, MTP-PE and RIBI, which contains three components extracted from bacteria, monophosphoryl lipid A, trehalose dimycolate and cell wall skeleton (MPL+TDM+CWS) in a 2% squalene/Tween 80 emulsion. Other examples of adjuvants include DDA (dimethyldioctadecylammonium bromide), Freund's complete and incomplete adjuvants and QuilA. In addition, immune modulating substances such as lymphokines (e.g., IFN-[gamma], IL-2 and IL- 12) or synthetic IFN-[gamma] inducers such as poly I:C can be used in combination with adjuvants described herein.

[0040] Vaccines may include an effective amount of the antibody-antigen fusion protein (Ab.Ag) or the antibody-antigen complex (Ab:Ag), dissolved or dispersed in a pharmaceutically acceptable carrier or aqueous medium. Such compositions can also be referred to as inocula. The use of such media and agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients also can be incorporated into the compositions. The compositions of the present invention may include classic pharmaceutical preparations. Dispersions also can be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.

[0041] Administration of vaccines according to the present invention will be via any common route so long as the target tissue is available via that route in order to maximize the delivery of antigen to a site for maximum (or in some cases minimum) immune response. Administration will generally be by orthotopic, intradermal, mucosally, subcutaneous, intramuscular, intraperitoneal or intravenous injection. Other areas for delivery include: oral, nasal, buccal, rectal, vaginal or topical. Vaccines of the invention are preferably administered parenterally, by injection, for example, either subcutaneously or intramuscularly. [0042] Vaccines may be administered in a manner compatible with the dosage formulation, and in such amount as will be prophylactically and/or therapeutically effective. The quantity to be administered depends on the subject to be treated, including, e.g., capacity of the subject's immune system to synthesize antibodies, and the degree of protection or treatment desired. Suitable dosage ranges are of the order of several hundred micrograms active ingredient per vaccination with a range from about 0.1 mg to 1000 mg, such as in the range from about 1 mg to 300 mg, or in the range from about 10 mg to 50 mg. Suitable regiments for initial administration and booster shots are also variable but are typified by an initial administration followed by subsequent inoculations or other administrations. Precise amounts of active ingredient required to be administered depend on the judgment of the practitioner and may be peculiar to each subject. It will be apparent to those of skill in the art that the therapeutically effective amount of nucleic acid molecule or fusion polypeptides of this invention will depend, inter alia, upon the administration schedule, the unit dose of antigen administered, whether the antibody-antigen fusion protein (Ab.Ag) or the antibody- antigen complex (Ab:Ag) is administered in combination with other therapeutic agents, the immune status and health of the recipient, and the therapeutic activity of the particular the Ab.Ag or the Ab:Ag.

[0043] A vaccine may be given in a single dose schedule or in a multiple dose schedule. A multiple dose schedule is one in which a primary course of vaccination may include, e.g., 1 -10 separate doses, followed by other doses given at subsequent time intervals required to maintain and or reinforce the immune response, for example, at 1 -4 months for a second dose, and if needed, a subsequent dose(s) after several months. Periodic boosters at intervals of 1 -5 years, usually 3 years, are desirable to maintain the desired levels of protective immunity. The course of the immunization can be followed by in vitro proliferation assays of peripheral blood lymphocytes (PBLs) co-cultured with ESAT6 or ST- CF, and by measuring the levels of IFN-[gamma] released from the primed lymphocytes. The assays may be performed using conventional labels, such as radionucleotides, enzymes, fluorescent labels and the like. These techniques are known to one skilled in the art and can be found in U.S. Pat. Nos. 3,791 ,932, 4,174,384 and 3,949,064, relevant portions incorporated by reference.

[0044] A vaccine may be provided in one or more "unit doses". Unit dose is defined as containing a predetermined-quantity of the vaccine calculated to produce the desired responses in association with its administration, i.e., the appropriate route and treatment regimen. The quantity to be administered, and the particular route and formulation, are within the skill of those in the clinical arts. The subject to be treated may also be evaluated, in particular, the state of the subject's immune system and the protection desired. A unit dose need not be administered as a single injection but may include continuous infusion over a set period of time. Unit dose of the present invention may conveniently may be described in terms of DNA/kg (or protein/Kg) body weight, with ranges between about 0.05, 0.10, 0.15, 0.20, 0.25, 0.5, 1, 10, 50, 100, 1,000 or more mg/DNA or protein/kg body weight are administered. Likewise the amount of vaccine delivered can vary from about 0.2 to about 8.0 mg/kg body weight. Thus, in particular embodiments, 0.4 mg/kg, 0.5 mg/kg, 0.8 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3.0 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 5.5 mg/kg, 6.0 mg/kg, 6.5 mg/kg, 7.0 mg/kg and 7.5 mg/kg of the antibody-producing agent in the vaccine may be delivered to an individual in vivo. The dosage of vaccine to be administered depends to a great extent on the weight and physical condition of the subject being treated as well as the route of administration and the frequency of treatment. [0045] In another aspect, embodiments relate to a combined HIV vaccine comprising a first HIV vaccine as described above and a second HIV vaccine. Therefore, in some methods a patient may be administered both an HIV vaccine composition discussed above, such as a dendritic-cell antibody attached to an HIV antigen, and a recombinant attenuated poxvirus that encodes for at least one HIV antigen. It is contemplated that in some embodiments the recombinant attenuated poxvirus is administered after the first HIV vaccine composition has been administered. It is further contemplated that the HIV antigens provided to the patient in the first and second HIV vaccines may be the same or they may be different. It is also contemplated that the administration of the first and second vaccines can be reversed such that the second vaccine is administered first and the first vaccine is administered second. It additionally contemplated that the first and second vacccines be administered at the same time. In instances when the first and second vaccines are not administered at the same time it is contemplated that the vaccines may be administered 1 , 2, 3, 4, 5, 6, 7,8 ,9, 10, 1 1, 12, 13 or 14 days apart or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48 ,49, 50, 51 or 52 weeks apart or 1 , 2, 3, 4, 5, 6, 7,8 ,9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 36, 48, 60, 72, 84 or 96 months apart or 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19 or 20 years apart.

[0046] In one embodiment, the second HIV vaccine is selected from the group consisting of an attenuated recombinant virus, a naked DNA vaccine and a DC-targeting vaccine.

[0047] As used herein, the term "attenuated recombinant virus" refers to a virus that has been genetically altered by modern molecular biological methods, e. g. restriction endonuclease and ligase treatment, and rendered less virulent than wild type, typically by deletion of specific genes or by serial passage in a non-natural host cell line or at cold temperatures.

[0048] In one particular embodiment, the attenuated recombinant virus is an attenuated recombinant poxvirus.

[0049] "Poxviruses" are large, enveloped viruses with double-stranded DNA that is covalently closed at the ends. Pox viruses replicate entirely in the cytoplasm, establishing discrete centers of viral synthesis. Their use as vaccines has been known since the early 1980's (see, e. g. Panicali, et al, 1983). [0050] In one particular embodiment, the attenuated recombinant poxvirus is selected from the group consisting of NYVAC, ALVAC and MVA virus. In one embodiment, the NYVAC virus is a NYVAC-KC virus.

[0051] In another particular embodiment, the DC-targeting vaccine is a vaccine comprising an anti-DC receptor antibody or a fragment thereof to which at least one HIV antigen is fused or conjugated to form an antibody-antigen fusion protein (Ab.Ag) or an antibody-antigen complex (Ab:Ag).

[0052] As used herein, the term "anti-DC receptor antibody" refers to an antibody which specifically binds to a receptor on a dendritic cell. Such an antibody may be a monoclonal antibody (mAb) or have regions from a mAb, which is used for delivering at least one HIV antigen directly to the human dendritic cell for antigen uptake and presentation to antigen-specific T and B cells. Such antibody may also have associated DC activation properties evoked through the binding of the mAb to the DC receptor (e.g., the agonistic anti- CD40 antibody). [0053] In some embodiments, the mAb is humanized (i.e., converted to a sequence which retains the original key residues crucial for receptor binding, but has variable region framework and constant region sequences that are typically found in human antibodies).

[0054] Non-limiting examples of anti-DC receptor antibodies include, but are not limited to, antibodies which specifically binds to MHC class I, MHC class II, CD1 , CD2, CD3, CD4, CD8, CDl lb, CD14, CD15, CD16, CD19, CD20, CD29, CD31, CD40, CD43, CD44, CD45, CD54, CD56, CD57, CD58, CD83, CD86, CMRF-44, CMRF-56, DCIR, DC- ASGPR, CLEC-6, CD40, BDCA-2, MARCO, DEC-205, mannose receptor, Langerin, DECTIN-1 , B7-1 , B7-2, IFN-γ receptor and IL-2 receptor, ICAM-1 , Fey receptor and ASGPR. [0055] In certain embodiments, the anti-DC receptor antibody is selected from the group consisting of an anti-Dectin-1 antibody, an anti-DC-ASGPR, an anti-DCIR antibody, an anti-CLEC-6, an anti-CD40 antibody and an anti-Langerin antibody.

[0056] As used herein, the term "vaccine" is intended to mean a composition which can be administered to humans or to animals in order to induce an immune system response; this immune system response can result in a production of antibodies or simply in the activation of certain cells, in particular antigen-presenting cells, T lymphocytes and B lymphocytes. In certain embodiments the vaccine is capable of producing an immune response that leads to the production of neutralizing antibodies in the patient with respect to the antigen provided in the vaccine. The vaccine can be a composition for prophylactic purposes or for therapeutic purposes, or both. [0057] As used herein, the term "antigen" refers to any antigen that can be used in a vaccine, whether it involves a whole microorganism or a portion thereof, and various types: (e.g., peptide, protein, glycoprotein, polysaccharide, glycolipid, lipopeptide, etc). Thus, the term "antigen" refers to a molecule that can initiate a humoral and/or cellular immune response in a recipient of the antigen. The antigen is usually a molecule that causes a disease for which a vaccination would be advantageous treatment. Within the context of the invention, the antigens are human immunodeficiency virus (HIV) antigens; the term "antigen" also comprises the polynucleotides, the sequences of which are chosen so as to encode the antigens whose expression by the individuals to which the polynucleotides are administered is desired, in the case of the immunization technique referred to as DNA immunization.

[0058] As used herein, the term "antibodies" refers to immunoglobulins, whether natural or partially or wholly produced artificially, e.g. recombinant. An antibody may be monoclonal or polyclonal. The antibody may, in some cases, be a member of one, or a combination immunoglobulin classes, including: IgG, IgM, IgA, IgD, and IgE.

[0059] As used herein, the term "antibody or fragment thereof," includes whole antibodies or fragments of an antibody, e.g., Fv, Fab, Fab', F(ab')2, Fc, and single chain Fv fragments (ScFv) or any biologically effective fragments of an immunoglobulins that binds specifically to, e.g., LOX-1. Antibodies from human origin or humanized antibodies have lowered or no immunogenicity in humans and have a lower number or no immunogenic epitopes compared to non-human antibodies. Antibodies and their fragments will generally be selected to have a reduced level or no antigenicity in humans. A polypeptide that has one or more CDRs from a monoclonal antibody and that may have at least as good as a binding specificity and/or affinity of a monoclonal antibody may be referred to as an "antibody fragment" or a polypeptide comprises an antibody fragment.

[0060] Typically, the term "antibody or fragment thereof describes a recombinant antibody system that has been engineered to provide a target specific antibody. The monoclonal antibody made using standard hybridoma techniques, recombinant antibody display, humanized monoclonal antibodies and the like. The antibody can be used to, e.g., target (via one primary recombinant antibody against an internalizing receptor, e.g., a human dendritic cell receptor such as a LOX-1, CD40) one or several antigens and/or one adjuvant to dendritic cells. Any embodiment discussed in the context of an antibody may be implemented in the context of an antibody fragment, including a polypeptide comprising one or more CDRs from an antibody.

[0061] As used herein, the term "anti-Lectin-like oxidized LDL receptor-1 (LOX-1) antibody" refers to an antibody which specifically binds to LOX-1. In certain embodiments, a LOX-1 antibody or antibody discussed herein has a D of at least about or at most about 10^{" 6}, 10^"7, 10^"8, 10^"9, 10^"10 M or any range derivable therein.

[0062] As used herein, the term "monoclonal antibody" refers to an antibody composition having a homogeneous antibody population. The term is not limited regarding the species or source of the antibody, nor is it intended to be limited by the manner in which it is made. The term encompasses whole immunoglobulins as well as fragments such as Fab, F(ab')2, Fv, and other fragments that exhibit immunological binding properties of the parent monoclonal antibody molecule.

[0063] As used herein, the term "antigen-binding site" or "binding portion" refers to the part of the immunoglobulin molecule that participates in antigen binding. The antigen binding site is formed by amino acid residues of the N-terminal variable ("V") regions of the heavy ("H") and light ("L") chains. Three highly divergent stretches within the V regions of the heavy and light chains are referred to as "hypervariable regions" which are interposed between more conserved flanking stretches known as "framework regions" (FRs). As used herein, the term "FR" refers to amino acid sequences which are found naturally between and adjacent to hypervariable regions in immunoglobulins. In an antibody molecule, the three hypervariable regions of a light chain and the three hypervariable regions of a heavy chain are disposed relative to each other in three dimensional space to form an antigen-binding surface. The antigen-binding surface is complementary to the three-dimensional surface of a bound antigen, and the three hypervariable regions of each of the heavy and light chains are referred to as "complementarity-determining regions" or "CDRs".

[0064] As used herein, the term "humanized" antibody refers to those molecules comprising an antigen-binding site derived from a non-human immunoglobulin have been described, including chimeric antibodies having rodent V regions and their associated CDRs fused to human constant domains, rodent CDRs grafted into a human supporting FR prior to fusion with an appropriate human antibody constant domain, and rodent CDRs supported by recombinantly veneered rodent FRs. These "humanized" molecules are designed to minimize unwanted immunological response toward rodent antihuman antibody molecules, which limits the duration and effectiveness of therapeutic applications of those moieties in human recipients.

[0065] The terms "adjuvant" or "immunoadjuvant" may be used interchangeably and refer to a substance that enhances, augments or potentiates the host's immune response to an antigen, e.g., an antigen that is part of a vaccine. Non-limiting examples of some commonly used vaccine adjuvants include insoluble aluminum compounds, calcium phosphate, liposomes, Virosomes™, 1SCOMS®, microparticles (e.g., PLG), emulsions (e.g., MF59, Montanides), virus-like particles & viral vectors. PolylCLC (a synthetic complex of carboxymethylcellulose, polyinosinic-polycytidylic acid, and poly-L-lysine double-stranded RNA), which is a TLR3 agonist, is used as an adjuvant in the present invention. It will be understood that other TLR agonists may also be used (e.g. TLR4 agonists, TLR5 agonists, TLR7 agonists, TLR9 agonists; also as described in PCT publication number WO/2012/021834 or WO/2012/122396, the contents of which are incorporated herein by reference), or any combinations or modifications thereof.

[0066] As used herein, the term "conjugate" refers to any substance formed from the joining together of two parts. Representative conjugates in accordance with the present invention include those formed by joining together of the antigen with the antibody and/or the adjuvant. The term "conjugation" refers to the process of forming the conjugate and is usually done by physical coupling, e.g. covalent binding, co-ordination covalent, or secondary binding forces, e.g. Van der Waals bonding forces. The process of linking the antigen to the antibody and/or to the adjuvant can also be done via a non-covalent association such as a dockerin-cohesin association (as described in U.S. Patent Publication No. 20100135994, Banchereau et al. relevant portions incorporated herein by reference) or by a direct chemical linkage by forming a peptide or chemical bond.

[0067] As used herein, "Dendritic Cells" (DCs) refers to any member of a diverse population of morphologically similar cell types found in lymphoid or non-lymphoid tissues. These cells are characterized by their distinctive morphology, high levels of surface MHC- class II expression (Steinman, et al, 1991 ); incorporated herein by reference for its description of such cells). These cells can be isolated from a number of tissue sources, and conveniently, from peripheral blood, as described herein. [0068] As used herein, the term "HIV" refers to the human immunodeficiency virus. HIV includes, without limitation, HIV-1 . HIV may be either of the two known types of HIV, i.e., HIV-1 or HIV-2. The HIV-1 virus may represent any of the known major subtypes or clades (e.g., Classes A, B, C, D, E, F, G, J, and H) or outlying subtype (Group 0). Also encompassed are other HIV-1 subtypes or clades that may be isolated.

[0069] Methods are provided for preventing or treating an HIV infection comprising administering to a patient an HIV vaccine or a combination of vaccines as discussed above or herein. In certain embodiments, there are methods for inducing an immune response to at least one HIV epitope comprising administering to a patient an HIV vaccine or a combination of vaccines as discussed above or herein. Other methods are provided for potentiating an immune response to at least one HIV epitope comprising administering to a patient an HIV vaccine or a combination of vaccines as discussed above or herein.

[0070] In further embodiments there are methods of treating a patient in the early stages of an HIV infection comprising administering comprising administering to the patient an HIV vaccine or a combination of vaccines as discussed above or herein.

[0071] In some cases, there are methods of treating a patient comprising administering to the patient an HIV vaccine or a combination of vaccines as discussed above or herein.

[0072] Methods may involve a patient tested for an HIV infection, a patient determined to be infected with HIV, a patient with symptoms of early stage HIV infection, a patient who is at risk for HIV infection, a patient whose HIV infection status is known, or a patient previously treated for HIV infection. In certain embodiments, the patient is a patient who is pregnant. In other embodiments, a patient is a pediatric patient whose mother was infected with HIV. In other embodiments, the patient is a pediatric patient above the age of 13 years old. In certain embodiments, the patient has been exposed to HIV.

[0073] In some embodiments, methods further comprise testing the patient for HIV infection or diagnosing a patient with HIV infection. Additional methods may also involve treating a patient also with other HIV treatments such as HIV/AIDS small molecule treatments. [0074] In certain aspects, methods further comprise generating a neutralizing antibody. In certain instances, said method comprises administering an HIV vaccine composition comprising a dendritic cell targeting complex comprising an anti-LOX-1 antibody or an anti-CD40 antibody, or a fragment thereof, attached to at least one HIV antigen. In additional aspects, at least one HIV antigen is selected from the group consisting of HIV Gag, Pol, Pro, Tat, Nef, Rev, Vif, Vpr or Env antigens. In further embodiments, the Env antigen is gp41, gpl20, gpl40 or gpl40 with a C-terminal deletion. In yet other embodiments the method of generating neutralizing antibodies, further comprising an adjuvant. In other embodiments the adjuvant is conjugated to said anti-LOX-1 antibody or anti-CD40 antibody or fragment thereof and/or to at least one HIV antigen.

[0075] Any embodiment discussed in the context of an antibody may be implemented in any method embodiment discussed herein.

[0076] As used herein the specification, "a" or "an" may mean one or more. As used herein in the claim(s), when used in conjunction with the word "comprising", the words "a" or "an" may mean one or more than one.

[0077] The use of the term "or" in the claims is used to mean "and/or" unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and "and/or." As used herein "another" may mean at least a second or more. [0078] Throughout this application, the term "about" is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects.

[0079] Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0080] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.

[0081] FIG. 1. Analysis of purified hAnti-LOX-lVH3VKl -hIgG4-Flex-vl - ViralenvHIV-gpl40-Z-6xHis (two batches) and hAnti-LOX-l-VH3VKl-hIgG4 binding to immobilized human LOX-1 ectodomain protein. Dilutions of the test antibodies were incubated at the indicated concentrations with to immobilized human LOX-1 ectodomain protein coated at a fixed concentration on a solid surface. After washing, the plates were developed with a anti-Human IgG Fc-HRP reagent. Control (non-LOX-1 -binding mAbs) score like the background control (green lower curve) in this assay, which indicates that these humanized anti-LOX-1 antibody with or without fused to HIV ENV gpl40 have equal affinity for the human LOX-1 ectodomain. [0082] FIG. 2. Shows the T cell responses for Group 1 , which were first vaccinated twice with NYVAC, then twice with anti-LOX-l-ENV with Poly ICLC adjuvant. The data show clear T cell responses resulting from the NYVAC vaccine for all HIV antigens, but the anti-LOX-l-ENV + Poly ICLC vaccine boosts specifically the ENV-specific T cells, even after just one administration. [0083] FIG. 3. Shows the T cell responses for Group 2, which were first vaccinated twice with NYVAC, then twice with anti-LOX-l-ENV with PLA adjuvant. The data show clear T cell responses resulting from the NYVAC vaccine for all HIV antigens, but the anti- LOX-l -ENV + vaccine boosts specifically the ENV-specific T cells, but much more modestly than when co-administered with the poly ICLC adjuvant. [0084] FIG. 4. Shows the T cell responses for Group 3, which were vaccinated twice with anti-LOX-l -ENV with Poly ICLC adjuvant. The data show clear T cell responses resulting from the second (boost) anti-LOX-l -ENV + Poly ICLC vaccine administration specifically for ENV-specific T cells, showing this vaccine combination alone can elicit such a specific cellular response. [0085] FIG. 5. Shows the T cell responses for Group 4, which were vaccinated twice with anti-LOX-l -ENV with PLA adjuvant. The data show no clear T cell responses resulting from the anti-LOX- l -ENV + PLA vaccine administration specifically for ENV-specific T cells, showing this vaccine combination alone cannot readily elicit such a specific cellular response.

[0086] FIG. 6. Group 1 IFNg ELISPOT and serum Env-IgG.

[0087] FIG. 7. Group 2 NYVAC prime and antiLox-l-Env/GLA boost.

[0088] FIG. 8. Group 3 antiLox- 1 -Env/polylCLC prime & NYVAC boost.

[0089] FIG. 9. Group 4 antiLox- 1-Env/GLA prime & NYVAC boost.

[0090] FIG. 10. AUP518 study summary IFNg ELISPOT and Env-IgG.

[0091 ] FIG. 11. AUP518 total T cell responses by ICS.

[0092] FIG. 12. AUP518 CD4⁺ T cell epitope targets.

[0093] FIG. 13. AUP518 CD8⁺ T cell epitope targets.

[0094] FIG. 14. AUP518 anti-Env IgG magnitude in plasma.

[0095] FIG. 15. AUP 518 IgG response rate - VI V2.

[0096] FIG. 16. DC targeting ENV vaccines - QA.

[0097] FIG. 17. Expansion of Env-specific T cells in vitro.

[0098] FIG. 18. Env-fusion test using a specific CD4⁺ T cell clone.

[0099] FIG. 19. aCD40 12E12 mAb activates human B cells.

[00100] FIG. 20. aCD40-Env proteins up-regulate surface CD86 on human B cells.

[00101] FIG. 21. aCD40-Env proteins induce proliferation of human B cells.

[00102J FIG. 22. Enhanced DC targeting Env vaccines.

[00103] FIG. 23. Enhanced DC targeting Env vaccines. [00104] FIG. 24. aCD40-Env proteins activate human B cells.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[00105] As described in the Examples, an anti-LOX-1 antibody to which a HIV

Env antigen has been fused (called hereafter anti-Loxl gpl40 vaccine) has been shown to induce a strong immune response against said antigen (including a strong T cell response and B cell response in non human primates (NHP)). This provides an efficient and effective HIV vaccine. Moreover, an anti-Loxl g l40 vaccine has been used in a prime-boost strategy in combination with a NYVAC-KC poxvirus encoding several HIV antigens including HIV Env antigen. It has been demonstrated that said anti-Loxl gpl40 vaccine efficiently boosts a prime vaccination with the poxvirus and that the response is highly specific for Env antigen.

I. NUCLEIC ACIDS

[00106] In certain embodiments, there are recombinant nucleic acids encoding the proteins, polypeptides, or peptides described herein. Polynucleotide contemplated for use in methods and compositions include those encoding antibodies to DC receptors or binding portions thereof.

[00107] As used in this application, the term "polynucleotide" refers to a nucleic acid molecule that either is recombinant or has been isolated free of total genomic nucleic acid. Included within the term "polynucleotide" are oligonucleotides (nucleic acids 100 residues or fewer in length), recombinant vectors, including, for example, plasmids, cosmids, phage, viruses, and the like. Polynucleotides include, in certain aspects, regulatory sequences, isolated substantially away from their naturally occurring genes or protein encoding sequences. Polynucleotides may be single-stranded (coding or antisense) or double-stranded, and may be RNA, DNA (genomic, cDNA or synthetic), analogs thereof, or a combination thereof. Additional coding or non-coding sequences may, but need not, be present within a polynucleotide.

[00108] In this respect, the term "gene," "polynucleotide," or "nucleic acid" is used to refer to a nucleic acid that encodes a protein, polypeptide, or peptide (including any sequences required for proper transcription, post-translational modification, or localization). As will be understood by those in the art, this term encompasses genomic sequences, expression cassettes, cDNA sequences, and smaller engineered nucleic acid segments that express, or may be adapted to express, proteins, polypeptides, domains, peptides, fusion proteins, and mutants. A nucleic acid encoding all or part of a polypeptide may contain a contiguous nucleic acid sequence encoding all or a portion of such a polypeptide. It also is contemplated that a particular polypeptide may be encoded by nucleic acids containing variations having slightly different nucleic acid sequences but, nonetheless, encode the same or substantially similar protein (see above).

[00109] In particular embodiments, there are isolated nucleic acid segments and recombinant vectors incorporating nucleic acid sequences that encode a polypeptide (e.g., an antibody or fragment thereof) that binds to DC receptors. The term "recombinant" may be used in conjunction with a polypeptide or the name of a specific polypeptide, and this generally refers to a polypeptide produced from a nucleic acid molecule that has been manipulated in vitro or that is a replication product of such a molecule.

[00110] The nucleic acid segments, regardless of the length of the coding sequence itself, may be combined with other nucleic acid sequences, such as promoters, polyadenylation signals, additional restriction enzyme sites, multiple cloning sites, other coding segments, and the like, such that their overall length may vary considerably. It is therefore contemplated that a nucleic acid fragment of almost any length may be employed, with the total length preferably being limited by the ease of preparation and use in the intended recombinant nucleic acid protocol. In some cases, a nucleic acid sequence may encode a polypeptide sequence with additional heterologous coding sequences, for example to allow for purification of the polypeptide, transport, secretion, post-translational modification, or for therapeutic benefits such as targeting or efficacy. As discussed above, a tag or other heterologous polypeptide may be added to the modified polypeptide-encoding sequence, wherein "heterologous" refers to a polypeptide that is not the same as the modified polypeptide.

[00111] In certain embodiments, there are polynucleotide variants having substantial identity to the sequences disclosed herein; those comprising at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or higher sequence identity, including all values and ranges there between, compared to a polynucleotide sequence provided herein using the methods described herein {e.g. , BLAST analysis using standard parameters). In certain aspects, the isolated polynucleotide will comprise a nucleotide sequence encoding a polypeptide that has at least 90%, preferably 95% and above, identity to an amino acid sequence described herein, over the entire length of the sequence; or a nucleotide sequence complementary to said isolated polynucleotide.

Vectors

[00112] Polypeptides may be encoded by a nucleic acid molecule. The nucleic acid molecule can be in the form of a nucleic acid vector. The term "vector" is used to refer to a carrier nucleic acid molecule into which a heterologous nucleic acid sequence can be inserted for introduction into a cell where it can be replicated and expressed. A nucleic acid sequence can be "heterologous," which means that it is in a context foreign to the cell in which the vector is being introduced or to the nucleic acid in which is incorporated, which includes a sequence homologous to a sequence in the cell or nucleic acid but in a position within the host cell or nucleic acid where it is ordinarily not found. Vectors include DNAs, RNAs, plasmids, cosmids, viruses (bacteriophage, animal viruses, and plant viruses), and artificial chromosomes (e.g., YACs). One of skill in the art would be well equipped to construct a vector through standard recombinant techniques (for example Sambrook et ai, 2001 ; Ausubel et ai, 1996, both incorporated herein by reference). Vectors may be used in a host cell to produce an antibody that binds a dendritic cell receptor.

[00113] The term "expression vector" refers to a vector containing a nucleic acid sequence coding for at least part of a gene product capable of being transcribed. In some cases, NA molecules are then translated into a protein, polypeptide, or peptide. Expression vectors can contain a variety of "control sequences," which refer to nucleic acid sequences necessary for the transcription and possibly translation of an operably linked coding sequence in a particular host organism. In addition to control sequences that govern transcription and translation, vectors and expression vectors may contain nucleic acid sequences that serve other functions as well and are described herein. Host Cells

[00114] As used herein, the terms "cell," "cell line," and "cell culture" may be used interchangeably. All of these terms also include their progeny, which is any and all subsequent generations. It is understood that all progeny may not be identical due to deliberate or inadvertent mutations. In the context of expressing a heterologous nucleic acid sequence, "host cell" refers to a prokaryotic or eukaryotic cell, and it includes any transformable organism that is capable of replicating a vector or expressing a heterologous gene encoded by a vector. A host cell can, and has been, used as a recipient for vectors or viruses. A host cell may be "transfected" or "transformed," which refers to a process by which exogenous nucleic acid, such as a recombinant protein-encoding sequence, is transferred or introduced into the host cell. A transformed cell includes the primary subject cell and its progeny.

[00115] Some vectors may employ control sequences that allow it to be replicated and/or expressed in both prokaryotic and eukaryotic cells. One of skill in the art would further understand the conditions under which to incubate all of the above described host cells to maintain them and to permit replication of a vector. Also understood and known are techniques and conditions that would allow large-scale production of vectors, as well as production of the nucleic acids encoded by vectors and their cognate polypeptides, proteins, or peptides.

Expression Systems

[00116] Numerous expression systems exist that comprise at least a part or all of the compositions discussed above. Prokaryote- and/or eukaryote-based systems can be employed for use with an embodiment to produce nucleic acid sequences, or their cognate polypeptides, proteins and peptides. Many such systems are commercially and widely available.

[00117] The insect cell/baculovirus system can produce a high level of protein expression of a heterologous nucleic acid segment, such as described in U.S. Patents 5,871 ,986, 4,879,236, both herein incorporated by reference, and which can be bought, for example, under the name MAXBAC® 2.0 from INVITROGEN® and BACPACK™ BACULOVIRUS EXPRESSION SYSTEM FROM CLONTECH®.

[00118] In addition to the disclosed expression systems, other examples of expression systems include S TRATAGENE® ' s COMPLETE CONTROL Inducible Mammalian Expression System, which involves a synthetic ecdysone-inducible receptor, or its pET Expression System, an E. coli expression system. Another example of an inducible expression system is available from INVITROGEN^®, which carries the T-REX™ (tetracycline-regulated expression) System, an inducible mammalian expression system that uses the full-length CMV promoter. INVITROGEN^® also provides a yeast expression system called the Pichia methanolica Expression System, which is designed for high-level production of recombinant proteins in the methyl otrophic yeast Pichia methanolica. One of skill in the art would know how to express a vector, such as an expression construct, to produce a nucleic acid sequence or its cognate polypeptide, protein, or peptide.

II. PROTEINACEOUS COMPOSITIONS

[00119] Substitutional variants typically contain the exchange of one amino acid for another at one or more sites within the protein, and may be designed to modulate one or more properties of the polypeptide, with or without the loss of other functions or properties. Substitutions may be conservative, that is, one amino acid is replaced with one of similar shape and charge. Conservative substitutions are well known in the art and include, for example, the changes of: alanine to serine; arginine to lysine; asparagine to glutamine or histidine; aspartate to glutamate; cysteine to serine; glutamine to asparagine; glutamate to aspartate; glycine to proline; histidine to asparagine or glutamine; isoleucine to leucine or valine; leucine to valine or isoleucine; lysine to arginine; methionine to leucine or isoleucine; phenylalanine to tyrosine, leucine or methionine; serine to threonine; threonine to serine; tryptophan to tyrosine; tyrosine to tryptophan or phenylalanine; and valine to isoleucine or leucine. Alternatively, substitutions may be non-conservative such that a function or activity of the polypeptide is affected. Non-conservative changes typically involve substituting a residue with one that is chemically dissimilar, such as a polar or charged amino acid for a nonpolar or uncharged amino acid, and vice versa. [00120] Proteins may be recombinant, or synthesized in vitro. Alternatively, a non-recombinant or recombinant protein may be isolated from bacteria. It is also contemplated that a bacteria containing such a variant may be implemented in compositions and methods. Consequently, a protein need not be isolated.

[00121] The term "functionally equivalent codon" is used herein to refer to codons that encode the same amino acid, such as the six codons for arginine or serine, and also refers to codons that encode biologically equivalent amino acids (see Table, below). Codon Table

Amino Acids Codons

Alanine Ala A GCA GCC GCG GCU

Cysteine Cys C UGC UGU

Aspartic acid Asp D GAC GAU

Glutamic acid Glu E GAA GAG

Phenylalanine Phe F UUC uuu

Glycine Gly G GGA GGC GGG GGU

Histidine His H CAC CAU

Isoleucine lie 1 AUA AUC AUU

Lysine Lys K AAA AAG

Leucine Leu L UUA UUG CUA CUC CUG CUU

Methionine Met M AUG

Asparagine Asn N AAC AAU

Proline Pro P CCA CCC CCG CCU

Glutamine Gin Q CAA CAG

Arginine Arg R AGA AGG CGA CGC CGG CGU

Serine Ser s AGC AGU UCA UCC UCG ucu

Threonine Thr T ACA ACC ACG ACU

Valine Val V GUA GUC GUG GUU

Tryptophan Trp w UGG

Tyrosine Tyr Y UAC UAU

[00122] It also will be understood that amino acid and nucleic acid sequences may include additional residues, such as additional N- or C-terminal amino acids, or 5' or 3' sequences, respectively, and yet still be essentially as set forth in one of the sequences disclosed herein, so long as the sequence meets the criteria set forth above, including the maintenance of biological protein activity where protein expression is concerned. The addition of terminal sequences particularly applies to nucleic acid sequences that may, for example, include various non-coding sequences flanking either of the 5' or 3' portions of the coding region.

[00123] The following is a discussion based upon changing of the amino acids of a protein to create an equivalent, or even an improved, second-generation molecule. For example, certain amino acids may be substituted for other amino acids in a protein structure without appreciable loss of interactive binding capacity with structures such as, for example, antigen-binding regions of antibodies or binding sites on substrate molecules. Since it is the interactive capacity and nature of a protein that defines that protein's biological functional activity, certain amino acid substitutions can be made in a protein sequence, and in its underlying DNA coding sequence, and nevertheless produce a protein with like properties. It is thus contemplated by the inventors that various changes may be made in the DNA sequences of genes without appreciable loss of their biological utility or activity.

[00124] In making such changes, the hydropathic index of amino acids may be considered. The importance of the hydropathic amino acid index in conferring interactive biologic function on a protein is generally understood in the art (Kyte and Doolittle, 1982). It is accepted that the relative hydropathic character of the amino acid contributes to the secondary structure of the resultant protein, which in turn defines the interaction of the protein with other molecules, for example, enzymes, substrates, receptors, DNA, antibodies, antigens, and the like. [00125] It also is understood in the art that the substitution of like amino acids can be made effectively on the basis of hydrophilicity. U.S. Patent 4,554, 101 , incorporated herein by reference, states that the greatest local average hydrophilicity of a protein, as governed by the hydrophilicity of its adjacent amino acids, correlates with a biological property of the protein. It is understood that an amino acid can be substituted for another having a similar hydrophilicity value and still produce a biologically equivalent and immunologically equivalent protein.

[00126] As outlined above, amino acid substitutions generally are based on the relative similarity of the amino acid side-chain substituents, for example, their hydrophobicity, hydrophilicity, charge, size, and the like. Exemplary substitutions that take into consideration the various foregoing characteristics are well known and include: arginine and lysine; glutamate and aspartate; serine and threonine; glutamine and asparagine; and valine, leucine and isoleucine.

[00127] It is contemplated that in compositions there is between about 0.001 mg and about 10 mg of total polypeptide, peptide, and/or protein per ml. Thus, the concentration of protein in a composition can be about, at least about or at most about 0.001 , 0.010, 0.050, 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1 .5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0 mg/ml or more (or any range derivable therein). Of this, about, at least about, or at most about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 , 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, 99, 100% may be an antibody that binds SpA, and may be used in combination with other staphylococcal proteins or protein-binding antibodies described herein.

Polypeptides and Polypeptide Production

[00128] Embodiments involve polypeptides, peptides, and proteins and immunogenic fragments thereof for use in various aspects described herein. For example, specific antibodies are assayed for or used in binding to DC receptors and presenting HIV antigens. In specific embodiments, all or part of proteins described herein can also be synthesized in solution or on a solid support in accordance with conventional techniques. Various automatic synthesizers are commercially available and can be used in accordance with known protocols. See, for example, Stewart and Young, (1984); Tarn et al. , (1983); Merrifield, (1986); and Barany and Merrifield (1979), each incorporated herein by reference. Alternatively, recombinant DNA technology may be employed wherein a nucleotide sequence that encodes a peptide or polypeptide is inserted into an expression vector, transformed or transfected into an appropriate host cell and cultivated under conditions suitable for expression.

[00129] One embodiment includes the use of gene transfer to cells, including microorganisms, for the production and/or presentation of proteins. The gene for the protein of interest may be transferred into appropriate host cells followed by culture of cells under the appropriate conditions. A nucleic acid encoding virtually any polypeptide may be employed. The generation of recombinant expression vectors, and the elements included therein, are discussed herein. Alternatively, the protein to be produced may be an endogenous protein normally synthesized by the cell used for protein production.

[00130] In a certain aspects an DC receptor fragment comprises substantially all of the extracellular domain of a protein which has at least 85% identity, at least 90% identity, at least 95% identity, or at least 97-99% identity, including all values and ranges there between, to a sequence selected over the length of the fragment sequence.

[00131] Also included in immunogenic compositions are fusion proteins composed of HIV antigens, or immunogenic fragments of HIV antigens (e.g. , gpl 40). HIV antigens may be from any type (e.g. HIV-1 , HIV-2), group (e.g. group M, group N, group O, or group P), sub-type or clade (e.g. clade A, B, C, D, F, G, H, J, K) or circulating recombinant form of HIV. Alternatively, embodiments also include individual fusion proteins of HIV proteins or immunogenic fragments thereof, as a fusion protein with heterologous sequences such as a provider of T-cell epitopes or purification tags, for example: β- galactosidase, glutathione-S-transferase, green fluorescent proteins (GFP), epitope tags such as FLAG, myc tag, poly histidine, or viral surface proteins such as influenza virus haemagglutinin, or bacterial proteins such as tetanus toxoid, diphtheria toxoid, CRM197.

Antibodies and Antibody-Like Molecules

[00132] In certain aspects, one or more antibodies or antibody-like molecules (e.g., polypeptides comprsing antibody CDR domains) may be obtained or produced which have a specificity for DC receptor. These antibodies may be used in various diagnostic or therapeutic applications described herein.

[00133] As used herein, the term "antibody" is intended to refer broadly to any immunologic binding agent such as IgG, IgM, IgA, IgD and IgE as well as polypeptides comprsing antibody CDR domains that retain antigen binding activity. Thus, the term "antibody" is used to refer to any antibody-like molecule that has an antigen binding region, and includes antibody fragments such as Fab', Fab, F(ab')2, single domain antibodies (DABs), Fv, scFv (single chain Fv), and polypeptides with antibody CDRs, scaffolding domains that display the CDRs (e.g., anticalins) or a nanobody. For example, the nanobody can be antigen-specific VHH (e.g., a recombinant VHH) from a camelid IgG2 or IgG3, or a CDR-displaying frame from such camelid Ig. The techniques for preparing and using various antibody-based constructs and fragments are well known in the art. Means for preparing and characterizing antibodies are also well known in the art (See, e.g., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988; incorporated herein by reference).

[00134] "Mini-antibodies" or "minibodies" are also contemplated for use with embodiments. Minibodies are sFv polypeptide chains which include oligomerization domains at their C-termini, separated from the sFv by a hinge region (Pack, el ah, 1992). The oligomerization domain comprises self-associating a-helices, e.g., leucine zippers, that can be further stabilized by additional disulfide bonds. The oligomerization domain is designed to be compatible with vectorial folding across a membrane, a process thought to facilitate in vivo folding of the polypeptide into a functional binding protein. Generally, minibodies are produced using recombinant methods well known in the art. See, e.g., Pack et al. (1992); Cumber et al. (1992).

[00135] Antibody-like binding peptidomimetics are also contemplated in embodiments. Liu et al, 2003 describe "antibody like binding peptidomimetics" (ABiPs), which are peptides that act as pared-down antibodies and have certain advantages of longer serum half-life as well as less cumbersome synthesis methods.

[00136] Alternative scaffolds for antigen binding peptides, such as CDRs are also available and can be used to generate DC receptor-binding molecules in accordance with the embodiments. Generally, a person skilled in the art knows how to determine the type of protein scaffold on which to graft at least one of the CDRs arising from the original antibody. More particularly, it is known that to be selected such scaffolds must meet the greatest number of criteria as follows (Skerra, 2000): good phylogenetic conservation; known three- dimensional structure (as, for example, by crystallography, NMR spectroscopy or any other technique known to a person skilled in the art); small size; few or no post-transcriptional modifications; and/or easy to produce, express and purify.

[00137] The origin of such protein scaffolds can be, but is not limited to, the structures selected among: fibronectin and preferentially fibronectin type III domain 10, lipocalin, anticalin (Skerra, 2001 ), protein Z arising from domain B of protein A of Staphylococcus aureus, thioredoxin A or proteins with a repeated motif such as the "ankyrin repeat" (Kohl et al , 2003), the "armadillo repeat", the "leucine-rich repeat" and the "tetratricopeptide repeat". For example, anticalins or lipocalin derivatives are a type of binding proteins that have affinities and specificities for various target molecules and can be used as DC receptor-binding molecules. Such proteins are described in US Patent Publication Nos. 20100285564, 20060058510, 20060088908, 20050106660, and PCT Publication No. WO2006/056464, incorporated herein by reference.

[00138] Scaffolds derived from toxins such as, for example, toxins from scorpions, insects, plants, mollusks, etc., and the protein inhibiters of neuronal NO synthase (PIN) may also be used in certain aspects.

[00139] Monoclonal antibodies (MAbs) are recognized to have certain advantages, e.g., reproducibility and large-scale production. Embodiments include monoclonal antibodies of the human, murine, monkey, rat, hamster, rabbit and chicken origin.

[00140] "Humanized" antibodies are also contemplated, as are chimeric antibodies from mouse, rat, or other species, bearing human constant and/or variable region domains, bispecific antibodies, recombinant and engineered antibodies and fragments thereof. As used herein, the term "humanized" immunoglobulin refers to an immunoglobulin comprising a human framework region and one or more CDR's from a non-human (usually a mouse or rat) immunoglobulin. The non-human immunoglobulin providing the CDR's is called the "donor" and the human immunoglobulin providing the framework is called the "acceptor". A "humanized antibody" is an antibody comprising a humanized light chain and a humanized heavy chain immunoglobulin. In order to describe antibodies of some embodiments, the strength with which an antibody molecule binds an epitope, known as affinity, can be measured. The affinity of an antibody may be determined by measuring an association constant (Ka) or dissociation constant(Kd). Antibodies deemed useful in certain embodiments may have an association constant of about, at least about, or at most about 106, 107, 108,109 or 1010 M or any range derivable therein. Similarly, in some embodiments antibodies may have a dissoaciation constant of about, at least about or at most about 10-6, 10-7, 10-8, 10-9 or 10-10. M or any range derivable therein. These values are reported for antibodies discussed herein and the same assay may be used to evaluate the binding properties of such antibodies

[00141] In certain embodiments, a polypeptide that specifically binds to DC receptors is able to bind a DC receptor on the surface of the cells and present an HIV antigen that allows the generation of a robust immune response. Moreover, in some embodiments, the polypeptide that is used can provided protective immunity against HIV. 1. Methods for Generating Antibodies

[00142] Methods for generating antibodies (e.g., monoclonal antibodies and/or monoclonal antibodies) are known in the art. Briefly, a polyclonal antibody is prepared by immunizing an animal with a DC receptor polypeptide or a portion thereof in accordance with embodiments and collecting antisera from that immunized animal. [00143] A wide range of animal species can be used for the production of antisera. Typically the animal used for production of antisera is a rabbit, a mouse, a rat, a hamster, a guinea pig or a goat. The choice of animal may be decided upon the ease of manipulation, costs or the desired amount of sera, as would be known to one of skill in the art. It will be appreciated that antibodies can also be produced transgenically through the generation of a mammal or plant that is transgenic for the immunoglobulin heavy and light chain sequences of interest and production of the antibody in a recoverable form therefrom. In connection with the transgenic production in mammals, antibodies can be produced in, and recovered from, the milk of goats, cows, or other mammals. See, e.g., U.S. Pat. Nos. 5,827,690, 5,756,687, 5,750, 172, and 5,741 ,957.

[00144] As is also well known in the art, the immunogenicity of a particular immunogen composition can be enhanced by the use of non-specific stimulators of the immune response, known as adjuvants. Suitable adjuvants include any acceptable immunostimulatory compound, such as cytokines, chemokines, cofactors, toxins, plasmodia, synthetic compositions or vectors encoding such adjuvants.

|00145] Adjuvants that may be used in accordance with embodiments include, but are not limited to, IL-1, IL-2, IL-4, IL-7, IL-12, -interferon, GMCSP, BCG, aluminum hydroxide, MDP compounds, such as thur-MDP and nor-MDP, CGP (MTP-PE), lipid A, and monophosphoryl lipid A (MPL). RIBI, which contains three components extracted from bacteria, MPL, trehalose dimycolate (TDM) and cell wall skeleton (CWS) in a 2% squalene/Tween 80 emulsion is also contemplated. MHC antigens may even be used. Exemplary adjuvants may include complete Freund's adjuvant (a non-specific stimulator of the immune response containing killed Mycobacterium tuberculosis), incomplete Freund's adjuvants and/or aluminum hydroxide adjuvant.

[00146] In addition to adjuvants, it may be desirable to coadminister biologic response modifiers (BRM), which have been shown to upregulate T cell immunity or downregulate suppressor cell activity. Such BRMs include, but are not limited to, Cimetidine (CIM; 1200 mg/d) (Smith/Kline, PA); low-dose Cyclophosphamide (CYP; 300 mg/m2) (Johnson/ Mead, NJ), cytokines such as -interferon, IL-2, or IL-12 or genes encoding proteins involved in immune helper functions, such as B-7.

[00147] The amount of immunogen composition used in the production of antibodies varies upon the nature of the immunogen as well as the animal used for immunization. A variety of routes can be used to administer the immunogen including but not limited to subcutaneous, intramuscular, intradermal, intraepidermal, intravenous and intraperitoneal. The production of antibodies may be monitored by sampling blood of the immunized animal at various points following immunization.

[00148] MAbs may be readily prepared through use of well-known techniques, such as those exemplified in U.S. Patent 4, 196,265, incorporated herein by reference. Typically, this technique involves immunizing a suitable animal with a selected immunogen composition, e.g., a purified or partially purified protein, polypeptide, peptide or domain, be it a wild-type or mutant composition. The immunizing composition is administered in a manner effective to stimulate antibody producing cells. [00149] The methods for generating monoclonal antibodies (MAbs) generally begin along the same lines as those for preparing polyclonal antibodies. In some embodiments, Rodents such as mice and rats are used in generating monoclonal antibodies. In some embodiments, rabbit, sheep or frog cells are used in generating monoclonal antibodies. The use of rats is well known and may provide certain advantages (Goding, 1986, pp. 60 61). Mice (e.g., BALB/c mice)are routinely used and generally give a high percentage of stable fusions.

[00150] MAbs produced by either means may be further purified, if desired, using filtration, centrifugation and various chromatographic methods such as HPLC or affinity chromatography. Fragments of the monoclonal antibodies can be obtained from the monoclonal antibodies so produced by methods which include digestion with enzymes, such as pepsin or papain, and/or by cleavage of disulfide bonds by chemical reduction. Alternatively, monoclonal antibody fragments can be synthesized using an automated peptide synthesizer.

[00151] It is also contemplated that a molecular cloning approach may be used to generate monoclonal antibodies. In one embodiment, combinatorial immunoglobulin phagemid libraries are prepared from RNA isolated from the spleen of the immunized animal, and phagemids expressing appropriate antibodies are selected by panning using cells expressing the antigen and control cells. The advantages of this approach over conventional hybridoma techniques are that approximately 104 times as many antibodies can be produced and screened in a single round, and that new specificities are generated by H and L chain combination which further increases the chance of finding appropriate antibodies. [00152] Another embodiment concerns producing antibodies, for example, as is found in U.S. Patent No. 6,091 ,001 , which describes methods to produce a cell expressing an antibody from a genomic sequence of the cell comprising a modified immunoglobulin locus using Cre-mediated site-specific recombination is disclosed. The method involves first transfecting an antibody-producing cell with a homology-targeting vector comprising a lox site and a targeting sequence homologous to a first DNA sequence adjacent to the region of the immunoglobulin loci of the genomic sequence which is to be converted to a modified region, so the first lox site is inserted into the genomic sequence via site-specific homologous recombination. Then the cell is transfected with a lox-targeting vector comprising a second lox site suitable for Cre-mediated recombination with the integrated lox site and a modifying sequence to convert the region of the immunoglobulin loci to the modified region. This conversion is performed by interacting the lox sites with Cre in vivo, so that the modifying sequence inserts into the genomic sequence via Cre-mediated site-specific recombination of the lox sites. [00153] Alternatively, monoclonal antibody fragments can be synthesized using an automated peptide synthesizer, or by expression of full-length gene or of gene fragments in E. coli.

[00154] It is further contemplated that monoclonal antibodies may be further screened or optimized for properties relating to specificity, avidity, half-life, immunogenicity, binding association, binding disassociation, or overall functional properties relative to beinga treatment for infection. Thus, it is contemplated that monoclonal antibodies may have 1 , 2, 3, 4, 5, 6, or more alterations in the amino acid sequence of 1 , 2, 3, 4, 5, or 6 CDRs of monoclonal antibodies or humanized antibodies provided herein. It is contemplated that the amino acid in position 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 of CDR1 , CDR2, CDR3, CDR4, CDR5, or CDR6 of the VJ or VDJ region of the light or heavy variable region of antibodies may have an insertion, deletion, or substitution with a conserved or non-conserved amino acid. Such amino acids that can either be substituted or constitute the substitution are disclosed above.

[00155] In some embodiments, fragments of a whole antibody can perform the function of binding antigens. Examples of binding fragments are (i) the Fab fragment constituted with the VL, VH, CL and CHI domains; (ii) the Fd fragment consisting of the VH and CHI domains; (iii) the Fv fragment constituted with the VL and VH domains of a single antibody; (iv) the dAb fragment (Ward, 1989; McCafferty et al, 1990; Holt et al, 2003), which is constituted with a VH or a VL domain; (v) isolated CDR regions; (vi) F(ab')2 fragments, a bivalent fragment comprising two linked Fab fragments (vii) single chain Fv molecules (scFv) , wherein a VH domain and a VL domain are linked by a peptide linker which allows the two domains to associate to form an antigen binding site (Bird et al, 1988; Huston et al, 1988); (viii) bispecific single chain Fv dimers (PCT/US92/09965) and (ix) "diabodies", multivalent or multispecific fragments constructed by gene fusion (WO94/13804; Holliger et al, 1993) . Fv, scFv or diabody molecules may be stabilized by the incorporation of disulphide bridges linking the VH and VL domains (Reiter et al, 1996). Minibodies comprising a scFv joined to a CH3 domain may also be made (Hu et al. 1996). The citations in this paragraph are all incorporated by reference.

[00156] Antibodies also include bispecific antibodies. Bispecific or bifunctional antibodies form a second generation of monoclonal antibodies in which two different variable regions are combined in the same molecule (Holliger & Winter, 1999). Their use has been demonstrated both in the diagnostic field and in the therapy field from their capacity to recruit new effector functions or to target several molecules on the surface of tumor cells. Where bispecific antibodies are to be used, these may be conventional bispecific antibodies, which can be manufactured in a variety of ways (Holliger et al, 1993), e.g. prepared chemically or from hybrid hybridomas, or may be any of the bispecific antibody fragments mentioned above. These antibodies can be obtained by chemical methods (Glennie et al, 1987; Repp et al, 1995) or somatic methods (Staerz & Bevan, 1986) but likewise by genetic engineering techniques which allow the heterodimerization to be forced and thus facilitate the process of purification of the antibody sought (Merchand et al , 1998). Examples of bispecific antibodies include those of the BiTE™ technology in which the binding domains of two antibodies with different specificity can be used and directly linked via short flexible peptides. This combines two antibodies on a short single polypeptide chain. Diabodies and scFv can be constructed without an Fc region, using only variable domains, potentially reducing the effects of anti-idiotypic reaction. The citations in this paragraph are all incorporated by reference. [00157] Bispecific antibodies can be constructed as entire IgG, as bispecific

Fab'2, as Fab'PEG, as diabodies or else as bispecific scFv. Further, two bispecific antibodies can be linked using routine methods known in the art to form tetravalent antibodies. [00158] Bispecific diabodies, as opposed to bispecific whole antibodies, may also be particularly useful because they can be readily constructed and expressed in E. coli. Diabodies (and many other polypeptides such as antibody fragments) of appropriate binding specificities can be readily selected using phage display (WO94/13804) from libraries. If one arm of the diabody is to be kept constant, for instance, with a specificity directed against SpA, then a library can be made where the other arm is varied and an antibody of appropriate specificity selected. Bispecific whole antibodies may be made by alternative engineering methods as described in Ridgeway et al, 1996), which is hereby incorporated by reference.

Antibody and Polypeptide Conjugates

[00159] Embodiments provide antibodies and antibody-like molecules against

DC receptors, polypeptides and peptides that are linked to at least one agent to form an antibody conjugate or payload. In order to increase the efficacy of antibody molecules as diagnostic or therapeutic agents, it is conventional to link or covalently bind or complex at least one desired molecule or moiety. Such a molecule or moiety may be, but is not limited to, at least one effector or reporter molecule. Effector molecules comprise molecules having a desired activity, e.g., cytotoxic activity. Non-limiting examples of effector molecules which have been attached to antibodies include toxins, therapeutic enzymes, antibiotics, radiolabeled nucleotides and the like. By contrast, a reporter molecule is defined as any moiety which may be detected using an assay. Non-limiting examples of reporter molecules which have been conjugated to antibodies include enzymes, radiolabels, haptens, fluorescent labels, phosphorescent molecules, chemiluminescent molecules, chromophores, luminescent molecules, photoaffmity molecules, colored particles or ligands, such as biotin.

[00160] Certain examples of antibody conjugates are those conjugates in which the antibody is linked to a detectable label. "Detectable labels" are compounds and/or elements that can be detected due to their specific functional properties, and/or chemical characteristics, the use of which allows the antibody to which they are attached to be detected, and/or further quantified if desired.

[00161] Antibody conjugates include those intended primarily for use in vitro, where the antibody is linked to a secondary binding ligand and/or to an enzyme (an enzyme tag) that will generate a colored product upon contact with a chromogenic substrate. Examples of suitable enzymes include, but are not limited to, urease, alkaline phosphatase, (horseradish) hydrogen peroxidase or glucose oxidase. Preferred secondary binding ligands are biotin and/or avidin and streptavidin compounds. The use of such labels is well known to those of skill in the art and are described, for example, in U.S. Patents 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149 and 4,366,241 ; each incorporated herein by reference. [00162] Molecules containing azido groups may also be used to form covalent bonds to proteins through reactive nitrene intermediates that are generated by low intensity ultraviolet light (Potter & Haley, 1983). In particular, 2- and 8-azido analogues of purine nucleotides have been used as site-directed photoprobes to identify nucleotide binding proteins in crude cell extracts (Owens & Haley, 1987; Atherton et al, 1985). The 2- and 8- azido nucleotides have also been used to map nucleotide binding domains of purified proteins (Khatoon et al, 1989; King et al, 1989; and Dholakia et al, 1989) and may be used as antibody binding agents.

[00163] Several methods are known in the art for the attachment or conjugation of an antibody to its conjugate moiety. Some attachment methods involve the use of a metal chelate complex employing, for example, an organic chelating agent such a diethylenetriaminepentaacetic acid anhydride (DTP A); ethylenetriaminetetraacetic acid; N- chloro-p-toluenesulfonamide; and/or tetrachloro-3 -6 -diphenylglycouril-3 attached to the antibody (U.S. Patent Nos. 4,472,509 and 4,938,948, each incorporated herein by reference). Monoclonal antibodies may also be reacted with an enzyme in the presence of a coupling agent such as glutaraldehyde or periodate. Conjugates with fluorescein markers are prepared in the presence of these coupling agents or by reaction with an isothiocyanate. In U.S. Patent No. 4,938,948, imaging of breast tumors is achieved using monoclonal antibodies and the detectable imaging moieties are bound to the antibody using linkers such as methyl-p- hydroxybenzimidate or N-succinimidyl-3-(4-hydroxyphenyl propionate. [00164] In some embodiments, derivatization of immunoglobulins by selectively introducing sulfhydryl groups in the Fc region of an immunoglobulin, using reaction conditions that do not alter the antibody combining site are contemplated. Antibody conjugates produced according to this methodology are disclosed to exhibit improved longevity, specificity and sensitivity (U.S. Pat. No. 5,196,066, incorporated herein by reference). Site-specific attachment of effector or reporter molecules, wherein the reporter or effector molecule is conjugated to a carbohydrate residue in the Fc region have also been disclosed in the literature (O'Shannessy et al, 1987). This approach has been reported to produce diagnostically and therapeutically promising antibodies which are currently in clinical evaluation.

2. Dendritic cell specific antibodies

[00165] In certain aspects, antibodies used to target HIV antigens to dendritic cells are dendritic cell specific antibodies. Some of the antibodies that may be used for this purpose are known in the art.

[00166] In some embodiments anti-DC-IR antibodies are used to target HIV antigens to dendritic cells. One example includes anti-dendritic cell immunoreceptor monoclonal antibody conjugates, wherein the conjugate comprises antigenic peptides that are loaded or chemically coupled to the antibody. Such antibodies are described in US application no. 61/332,465 and are incorporated herein by reference.

[00167] In other embodiments anti-CD40 antibodies are used to target HIV antigens to dendritic cells. Compositions and methods for the expression, secretion and use of anti-CD40 antibodies as vaccines and antigen delivery vectors with one linked antigenic peptides are described in WO 2010/104761 ; all methods disclosed are incorporated herein by reference.

[00168] In certain aspects anti-LOX-1 antibodies are used to target HIV antigens to dendritic cells. One example of such an antibody can be used to target the LOX-1 receptor on immune cells and increase the effectiveness of antigen presentation by LOX-1 expressing antigen presenting cells. Examples of such LOX-1 antibodies are described in WO 2008/103953, the contents of which are incorporated herein by reference.

[00169] In other aspects anti-CLEC-6 antibodies are used to target HIV antigens to dendritic cells. One example of such antibodies include anti-CLEC-6 antibodies used to increase the effectiveness of antigen presentation by CLEC-6 expressing antigen presenting cells. Such antibodies are described in WO 2008/103947, the methods and contents of which are incorporated herein by reference.

[00170] In yet other embodiments anti-Dectin-1 antibodies are used to target

HIV antigens to dendritic cells. Anti-Dectin-1 antibodies that increase the effectiveness of antigen presentation by Dectin- 1 expressing antigen presenting cells are described in WO 2008/1 18587, the contents of which are incorporated herein by reference.

[00171] In certain aspects, peptide linkers are used to link an dendritic cell specific antibodies and HIV antigens to be presented. Peptide linkers may incorporate glycosylation sites or introduce secondary structure. Additionally these linkers increase the efficiency of expression or stability of the fusion protein and as a result the efficiency of antigen presentation to a dendritic cell. Such linkers may include SSVSPTTSVHPTPTSVPPTPTKSSP (SEQ ID NO :3);

PTSTPADSSTITPTATPTATPTIKG (SEQ ID NO :4); T VTPTATATP S AI VTTITPTATT P (SEQ ID NO :5); or

TNGSITVAATAPTVTPTV ATPSAA (SEQ ID NO :6). These examples and others are discussed in WO 2010/104747, the contents of which are incorporated herein by reference.

[00172] In other embodiments an immune adjuvant is directly fused to the dendritic cell specific antibody in order to enhance the efficacy of the vaccine. In certain aspects the immune adjuvant may be a toll-like receptor (TLR) agonist. TLR agonists comprise flagellins from Salmonella enterica or Vibrio cholerae. TLR agonists may be specific for certain TLR classes (i.e., TLR5, TLR7 or TLR9 agonists) and may be presented in any combination or as any modification. Examples of such immune adjuvants are described in WO 2012/021834, the contents of which are incorporated herein by reference. IV. METHODS OF TREATMENT

[00173] As discussed above, the compositions and methods of using these compositions can treat a subject (e.g. , prevent an HIV infection or evoke a robust immune response to HIV) having, suspected of having, or at risk of developing an infection or related disease, particularly those related to HIV. [00174] As used herein the phrase "immune response" or its equivalent

"immunological response" refers to a humoral (antibody mediated), cellular (mediated by antigen-specific T cells or their secretion products) or both humoral and cellular response directed against a protein, peptide, or polypeptide of the invention in a recipient patient. Treatment or therapy can be an active immune response induced by administration of immunogen or a passive therapy effected by administration of antibody, antibody containing material, or primed T-cells. [00175] For purposes of this specification and the accompanying claims the terms "epitope" and "antigenic determinant" are used interchangeably to refer to a site on an antigen to which B and/or T cells respond or recognize. B-cell epitopes can be formed both from contiguous amino acids or noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained on exposure to denaturing solvents whereas epitopes formed by tertiary folding are typically lost on treatment with denaturing solvents. An epitope typically includes at least 3, and more usually, at least 5 or 8-10 amino acids in a unique spatial conformation. Methods of determining spatial conformation of epitopes include those methods described in Epitope Mapping Protocols (1996). T cells recognize continuous epitopes of about nine amino acids for CD8 cells or about 13-15 amino acids for CD4 cells. T cells that recognize the epitope can be identified by in vitro assays that measure antigen-dependent proliferation, as determined by 3H-thymidine incorporation by primed T cells in response to an epitope (Burke et al, 1994), by antigen-dependent killing (cytotoxic T lymphocyte assay, Tigges et al, 1996) or by cytokine secretion.

[00176] The presence of a cell-mediated immunological response can be determined by proliferation assays (CD4 (+) T cells) or CTL (cytotoxic T lymphocyte) assays. The relative contributions of humoral and cellular responses to the protective or therapeutic effect of an immunogen can be distinguished by separately isolating IgG and T- cells from an immunized syngeneic animal and measuring protective or therapeutic effect in a second subject. As used herein and in the claims, the terms "antibody" or "immunoglobulin" are used interchangeably.

[00177] Optionally, an antibody or preferably an immunological portion of an antibody, can be chemically conjugated to, or expressed as, a fusion protein with other proteins. For purposes of this specification and the accompanying claims, all such fused proteins are included in the definition of antibodies or an immunological portion of an antibody.

[00178] In one embodiment a method includes treatment for a disease or condition caused by a HIV pathogen. In certain aspects embodiments include methods of treatment of HIV infection infection, such as an infection acquired from an HIV positive individual. In some embodiments, the treatment is administered in the presence of HIV antigens. Furthermore, in some examples, treatment comprises administration of other agents commonly used against viral infection, such as one or more antiviral or antiretroviral compounds.

[00179] The therapeutic compositions are administered in a manner compatible with the dosage formulation, and in such amount as will be therapeutically effective. The quantity to be administered depends on the subject to be treated. Precise amounts of active ingredient required to be administered depend on the judgment of the practitioner. Suitable regimes for initial administration and boosters are also variable, but are typified by an initial administration followed by subsequent administrations.

[00180] The manner of application may be varied widely. Any of the conventional methods for administration of a polypeptide therapeutic are applicable. These are believed to include oral application on a solid physiologically acceptable base or in a physiologically acceptable dispersion, parenterally, by injection and the like. The dosage of the composition will depend on the route of administration and will vary according to the size and health of the subject. [00181] In certain instances, it will be desirable to have multiple administrations of the composition, e.g., 2, 3, 4, 5, 6 or more administrations. The administrations can be at 1 , 2, 3, 4, 5, 6, 7, 8, to 5, 6, 7, 8, 9 ,10, 1 1, 12 twelve week intervals, including all ranges there between.

Combination Therapy

[00182] The compositions and related methods, particularly administration of an antibody that binds DC receptor and delivers an HIV antigen or a peptide to a patient/subject, may also be used in combination with the administration of traditional antiretroviral therapies. These include, but are not limited to, entry inhibitors, CCR5 receptor antagonists, nucleoside reverse transcriptase inhibitors, nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors and maturation inhibitors.

[00183] In one aspect, it is contemplated that a therapy is used in conjunction with antiviral or anti-retroviral treatment. Alternatively, the therapy may precede or follow the other agent treatment by intervals ranging from minutes to weeks. In embodiments where the other agents and/or a proteins or polynucleotides are administered separately, one would generally ensure that a significant period of time did not expire between the time of each delivery, such that the therapeutic composition would still be able to exert an advantageously combined effect on the subject. In such instances, it is contemplated that one may administer both modalities within about 12-24 h of each other and, more preferably, within about 6-12 h of each other. In some situations, it may be desirable to extend the time period for administration significantly, however, where several days (2, 3, 4, 5, 6 or 7) to several weeks (1 , 2, 3, 4, 5, 6, 7 or 8) lapse between the respective administrations.

[00184] In yet another aspect, a vaccine may be administered as part of a prime/boost strategy. A priming vaccine dose can be administered using a DC specific antibody fused to an HIV antigen in any of the embodiments described herein. A vaccine boost can be administered through the use of a second vaccine, either of the same type or from a different type of vaccine. Examples of such different vaccines include naked DNA vaccines or a recombinant poxvirus. A recombinant pox virus can be selected from the group comprising NYVAC, ALVAC and MVA virus. The second vaccine may comprise additional HIV antigens apart from the Env antigens that may be used in the first vaccine. It is also contemplated that the second vaccine may comprise an HIV protein such as an env protein plus an adjuvant either directly linked or administered independently.

[00185] Various combinations of therapy may be employed, for example antiviral or antiretroviral therapy is "A" and an antibody vaccine that comprises an antibody that binds a DC receptor and delivers an HIV antigen or a peptide or consensus peptide thereof is "B":

A/B/A B/A/B B/B/A A/A/B A/B/B B/A/A A/B/B/B B/A/B/B

B/B/B/A B/B/A/B A/A/B/B A/B/A/B A/B/B/A B/B/A/A

B/A/B/A B/A/A/B A/A/A/B B/A/A/A A/B/A/A A/A/B/A

[00186] Administration of the antibody compositions to a patient/subject will follow general protocols for the administration of such compounds, taking into account the toxicity, if any, of the composition. It is expected that the treatment cycles would be repeated as necessary. It is also contemplated that various standard therapies, such as hydration, may be applied in combination with the described therapy. General Pharmaceutical Compositions

[00187] In some embodiments, pharmaceutical compositions are administered to a subject. Different aspects may involve administering an effective amount of a composition to a subject. In some embodiments, an antibody that binds DC receptor and delivers an HIV antigen or a peptide or consensus peptide thereof may be administered to the patient to protect against or treat infection by one or more HIV subtypes. Alternatively, an expression vector encoding one or more such antibodies or polypeptides or peptides may be given to a patient as a preventative treatment. Additionally, such compositions can be administered in combination with an antibiotic. Such compositions will generally be dissolved or dispersed in a pharmaceutically acceptable carrier or aqueous medium.

[00188] The phrases "pharmaceutically acceptable" or "pharmacologically acceptable" refer to molecular entities and compositions that do not produce an adverse, allergic, or other untoward reaction when administered to an animal or human. As used herein, "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like. The use of such media and agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredients, its use in immunogenic and therapeutic compositions is contemplated. Supplementary active ingredients, such as other anti-infective agents and vaccines, can also be incorporated into the compositions.

[00189] The active compounds can be formulated for parenteral administration, e.g., formulated for injection via the mucosal, intravenous, intramuscular, sub-cutaneous, or even intraperitoneal routes. Typically, such compositions can be prepared as either liquid solutions or suspensions; solid forms suitable for use to prepare solutions or suspensions upon the addition of a liquid prior to injection can also be prepared; and, the preparations can also be emulsified.

[00190] The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions; formulations including sesame oil, peanut oil, or aqueous propylene glycol; and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases the form must be sterile and must be fluid to the extent that it may be easily injected. It also should be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms, such as bacteria and fungi.

[00191] The proteinaceous compositions may be formulated into a neutral or salt form. Pharmaceutically acceptable salts, include the acid addition salts (formed with the free amino groups of the protein) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, histidine, procaine and the like.

[00192] A pharmaceutical composition can include a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, by the maintenance of the required particle size in the case of dispersion, and by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin.

[00193] Sterile injectable solutions are prepared by incorporating the active compounds in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization or an equivalent procedure. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum- drying and freeze-drying techniques, which yield a powder of the active ingredient, plus any additional desired ingredient from a previously sterile-filtered solution thereof. [00194] Administration of the compositions will typically be via any common route. This includes, but is not limited to oral, nasal, or buccal administration. Alternatively, administration may be by orthotopic, intradermal, subcutaneous, intramuscular, intraperitoneal, intranasal, or intravenous injection. In certain embodiments, a vaccine composition may be inhaled (e.g. , U.S. Patent 6,651 ,655, which is specifically incorporated by reference). Such compositions would normally be administered as pharmaceutically acceptable compositions that include physiologically acceptable carriers, buffers or other excipients.

[00195] An effective amount of therapeutic or prophylactic composition is determined based on the intended goal. The term "unit dose" or "dosage" refers to physically discrete units suitable for use in a subject, each unit containing a predetermined quantity of the composition calculated to produce the desired responses discussed above in association with its administration, i.e. , the appropriate route and regimen. The quantity to be administered, both according to number of treatments and unit dose, depends on the protection desired.

[00196] Precise amounts of the composition also depend on the judgment of the practitioner and are peculiar to each individual. Factors affecting dose include physical and clinical state of the subject, route of administration, intended goal of treatment (alleviation of symptoms versus cure), and potency, stability, and toxicity of the particular composition. [00197] Upon formulation, solutions will be administered in a manner compatible with the dosage formulation and in such amount as is therapeutically or prophylactically effective. The formulations are easily administered in a variety of dosage forms, such as the type of injectable solutions described above.

V. EXAMPLES [00198] The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

EXAMPLE 1 -DC TARGETING ANTIBODY/HIV ANTIGEN FUSION CONSTRUCTS [00199] Below are given DNA and protein sequences for, respectively, the open reading frame and the predicted secreted product for proteins relevant to this application. mAnti- indicates the mouse variable region derived from the parental mouse hybridoma. H indicates H chain, LV indicated leader and variable region, hIgG4H-C indicates human IgG4 H chain constant region, Flex-vl indicates flexible linker sequence described in US 2010/0135994 Al , ViralenvHIV-gp indicates the HIV ENV sequence appended to the H chain C-terminus, and 6xHis indicates 6 H chain C-terminal Histidine residues. For production of DC-targeting vaccines containing direct fusions between antibody and antigen, mammalian expression vectors carrying both the H chain and L chain constructs are typically co-transfected. The L chain sequences are annotated to indicate the appropriate H chain pairing. 'S\ 'Z', 'C and 'B' designations refer to ENV sequences from different strains and/or clades of HIV.

[00200] A number of vectors for implementing an HIV vaccine have been prepared and expressed in CHO-S cells by stable transfection methods. Reduced SDS-PAGE analysis of purified proteins expressed by CHO-S cells stably transfected with vectors encoding C2891 [SLAML-6xHis-CthermoCohesin-ViralenvHIV-gpl40-Z-6xHis] and C2892 [SLAML-6xHis-CthermoCohesin-ViralenvHIV-gp l40-Z-del 6xHis] demonstrate expression of the full-length polypeptides encoded in each vector.

[00201] Reduced SDS-PAGE analysis of purified proteins expressed by CHO-S cells stably transfected with vectors encoding C2865 [hAnti-CD40VH3-LV-hIgG4H-C-Flex- vl -ViralenvHIV-gpl20-B-6xHis] and C2128 [hAnti-CD40VK2-LV-WgGK-C] demonstrate expression of the full-length polypeptides encoded in each vector.

[00202] Reduced SDS-PAGE analysis of purified proteins expressed by CHO-S cells stably transfected with vectors encoding C2424 [hAnti-CD40VH3-LV-hIgG4H-C-Flex- vl -ViralenvHIV-gpl40-Z-6xHis] and C2128 [hAnti-CD40VK2-LV-hIgG -C] demonstrate expression of the full-length polypeptides encoded in each vector [00203] Reduced SDS-PAGE analysis of purified proteins expressed by CHO-S cells stably transfected with vectors encoding C2289 [hAnti-LOX-1 VH3-LV-hIgG4H-C- Flex-vl -ViralenvHIV-gpl40-Z-6xHis] and C2266 [hAnti-LOX-1 VKl -LV-hlgG -C] demonstrate expression of the full-length polypeptides encoded in each vector [00204] Analysis of hAnti-LOX-1 -VH3VKl-hIgG4 and two individual preparations of purified hAnti-LOX-1 VH3V 1 -MgG4-Flex-vl-ViralenvHIV-gpl40-Z-6xHis binding to immobilized human LOX-1 ectodomain protein was performed. Dilutions of the test antibodies were incubated at concentrations in the range of lxlO^"5 to 100 nM with immobilized human LOX-1 ectodomain protein coated at a fixed concentration on a solid surface. After washing, the plates were developed with a anti-Human IgG Fc-HRP reagent. Control (non-LOX- 1 -binding mAbs) score like the background control (green lower curve) in this assay, which indicates that these humanized anti-LOX-l antibody with or without HIV ENV gpl40 fused have equal affinity for the human LOX-1 ectodomain (FIG 1).

[mAnti-LOX-l_15C4H-LV-hIgG4H-C] (as disclosed in patent WO 2008/103953)

EIQLQQTGPELV PGASVKISCKASGYPFTDYIMVWVKQSHGKSLEWIGNISPYYGTT NYNLKFKGKATLTVDKSSSTAYMQLNSLTSEDSAVYYCARSPNWDGAWFAHWGQ GALVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLV DYFPEPVTVSWNSGALTSG VHTFPAVLQSSGLYSLSSWTVPSSSLGT TYTCNVDHKPSNTKVDKRVESKYGPPCP PCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVH NAKT PREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQ PREPQ V YTLPPS QEEMTKNQ V SLTCLVKGF YP SDIA VE WESNGQPENN YKTTPP VLD SDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO :7)

C2272 [hAnti-LOX-lVH3-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-C-6xHis]

H chain secreted product IgG4H (underline), flexible linker {bold italics), gpl40 (bold underline) from HIV-1 CN54 (Clade C)

EIOLVOSGSEL KPGASV ISCKASGYPFTDYIMVWVROAPGKGLEWIGNISPYYGTT NY LKFKGRATLTVDKSTSTAYMELSSLRSEDTAVYYCARSPNWDGAWFAHWGOG ALVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLOSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPP CPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVH NAKTKPREEOFNSTYRVVSVLTVLHODWLNGKEYKCKVSNKGLPSSIEKTISKAKGQ PREPQVYTLPPSQEE TKNQVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPVLD SDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS >JP77Vr/ SVTPTNNSTPTNNSNPKPNPASNT V/YTVYYGVFWVKGATTTLFCASOAKAYmE VHNVWATHACVPADPNPOEMVLENVTENFNMW NEMVNQMOEDVISLWDOS LKPCVKLTPLCVTLECRNVSSNSNDTYHETYHESMKEMKNCSFNATTVVRDRK QTVYALFYRLDIVPLTKKNYSENSSEYYRLINCNTSAITOACPKVTFDPIPIHYCT PAGYAILKCNDKIFNGTGPCHNVSTVOCTHGIKPVVSTQLLLNGSLAEGEIIIRSE NLTNNVKTIIVHLNOSVEIVCTRPGNNTRKSIRIGPGQTFYATGDIIGDIROAHCN ISEDKWNETLQRVSK LAEHFONKTIKFASSSGGDLEVTTHSFNCRGEFFYCNTS GLFNGAYTPNGTKSNSSSIITIPCRIKOIINMWOEVGRAMYAPPIKGNITCKSNIT GLLLVRDGGTEPNDTETFRPGGGDMRNNWRSELYKYKVVEIKPLGVAPTTTKR RVVEREKSAVGIGAVFLGFLGVAGSTMGAASITLTVOAROLLSGIVOOQSNLLR AIEAOOHLLOLTVWGI OLQTRVLAIERYLKDOOLLGIWGCSGKLICTTAVPW NSSWSNKSQKEIWDNMTWMOWDKEISNYTNTVYRLLEESONQQERNE DLLA LDSHHHHHH (SEQ ID NO :8)

C2266 [hAnti-LOX- 1 VKl-LV-hlgGK-C]

L chain secreted product to pair with hAnti-LOX-lVH3-LV-hIgG4H-C-based fusion proteins

DIVLTQSPDSLAVSLGERATINCKASQSVDYDGDSYM WFQQKPGQPPKLLIYAASN LESGIPARFSGSGSGTDFTLT1NSLEEEDAATYYCQQSNEDPFTFGQGTKLEIKRTVAA PSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO :9)

C1773 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-S 6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTG ACTTGTTCTTTCTCTGGGTTTTC ACTGAGC ACTTCTGGTATGGGTCTG AG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTGTAGAAAAATTGTGGGTCACAG TCTATTATGGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATC AGATGCTAAAGCCTATGACACAGAGGTACATAATGTCTGGGCCACACATGCCTG TGTACCCACAGACCCTAACCCACAAGAAATAGTATTGGAAAATGTGACAGAAAA TTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAG TTTATGGGATCAAAGTCTAAAGCCATGTGTAAAGTTAACCCCACTCTGTGTTACT CTACATTGCACTAATTTGAAGAATGCTACTAATACCAAGAGTAGTAATTGGAAAG AGATGGACAGAGGAGAAATAAAAAATTGCTCTTTCAAGGTCACCACAAGCATAA GAAATAAGATGCAGAAAGAATATGCACTTTTTTATAAACTTGATGTAGTACCAAT AGATAATGATAATACAAGCTATAAATTGATAAATTGTAACACCTCAGTCATTACA CAGGCCTGTCCAAAGGTATCCTTTGAACCAATTCCCATACATTATTGTGCCCCGG CTGGTTTTGCGATTCTAAAGTGTAATGATAAGAAGTTCAATGGATCAGGACCATG TACAAATGTCAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTGTCAAC TCAATTGCTGTTAAATGGCAGTCTAGCAGAAGAAGGGGTAGTAATTAGATCTGA AAATTTCACAGACAATGCTAAAACTATAATAGTACAGCTGAAGGAATCTGTAGA AATTAATTGTACAAGACCTAACAATAATACAAGAAAAAGTATAACTATAGGACC GGGGAGAGCATTTTATGCAACAGGAGACATAATAGGAGATATAAGACAAGCACA TTGTAACATTAGTGGAGAAAAATGGAATAACACTTTAAAACAGATAGTTACAAA ATTACAAGCACAATTTGGGAATAAAACAATAGTCTTTAAGCAATCCTCAGGAGG GGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGT AATTCAACACAGCTTTTTAATAGTACTTGGAATAATACTATAGGGCCAAATAACA CTAATGGAACTATCACACTCCCATGCAGAATAAAACAAATTATAAACAGGTGGC AGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGACAAATTAGATGCT CATCAAATATTACAGGACTGCTATTAACAAGAGATGGTGGTAAAGAGATCAGTA ACACCACCGAGATCTTCAGACCTGGAGGTGGAGATATGAGGGACAATTGGAGAA GTGAATTATATAAATATAAAGTAGTAAAAATTGAGCCATTAGGAGTAGCACCCA CCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGTGACGCTAGGA GCTATGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACTATGGGCGCAGCGTCAC TGACGCTGACGGTACAGGCCAGACAATTATTGTCTGGTATAGTGCAACAGC AGA ACAATTTGCTGAGAGCTATTGAGGCGCAACAGCATCTGTTGCAACTCACAGTCTG GGGCATCAAGCAGCTCCAGGCAAGAGTCCTGGCTGTGGAAAGATACCTAAAGGA TCAACAGCTCCTAGGGATTTGGGGTTGCTCTGGAAAACTCATTTGCACCACTGCT GTGCCTTGGAATGCTAGTTGGAGTAATAAATCTCTGGATCAGATTTGGAATAACA TGACCTGGATGGAGTGGGAGAGAGAAATTGACAATTACACAAACTTAATATACA CCTTAATTGAAGAATCGCAGAACCAACAAGAAAAGAATGAACAAGAATTATTAG AATTGGATAAGTGGGCAAGTTTGTGGAATTGGTTTGACATATCAAAATGGCTGTG GTATATAAAAGCTAGCCACCATCACCATCACCATTGA (SEQ ID NO : 10) H chain secreted product IgG4H (underline), flexible linker {bold italics), pl40 (bold underline) from SF162, a clade B strain

OVTL ESGPGILOPSOTLSLTCSFSGFSLSTSGMGLSWIROPSGKGLEWLAHIYWDDD KRYNPSLKSRLTIS DTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLOSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP CPPCPAPEFEGGPSVFLFPP PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEY CKVSNKGLPSSIE TISKAK GOPREPOVYTLPPSQEEMTKNOVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPV LDSDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS07 T NTISVTPTNNSTPTNNSNPKPNPASVEKLW\TVYYG\FVV^KEATTTLFCASOAKA YDTEVHNVWATHACVPTDPNPQEIVLENVTENFNMWKNNMVEOMHEDIISLW DOSLKPCVKLTPLCVTLHCTNLKNATNTKSSNWKEMDRGEIKNCSFKVTTSIRN KMQKEYALFYKLDVVPIDNDNTSYKLINCNTSVITOACPKVSFEPIPIHYCAPAG FAILKCNDKKFNGSGPCTNVSTVOCTHGIRPVVSTQLLLNGSLAEEGVVIRSENF TDNAKTHVQLKESVEINCTRPNNNTRKSITIGPGRAFYATGDIIGDIROAHCNISG EKWNNTL OIVTKLOAQFGNKTIVFKOSSGGDPEIVMHSFNCGGEFFYCNSTOL FNSTWNNTIGPNNTNGTITLPCRIKQIINR QEVGKAMYAPPIRGOIRCSSNITGL LLTRDGGKEISNTTEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRR VVQREKRAVTLGAMFLGFLGAAGSTMGAASLTLTVOAROLLSGIVOOONNLLR AIEAOOHLLOLTVWGIKOLQARVLAVERYLKDOOLLGIWGCSGKLICTTAVPW NASWSNKSLDQIWNNMTWMEWEREIDNYTNLIYTLIEESQNOOEK EOELLEL DKWASLWNWFDISKWLWYIKASHHHHHH (SEQ ID NO :11) C1792 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-ViraIenvHIV-gpl20-S-6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTGTAGAAAAATTGTGGGTCACAG TCTATTATGGGGTACCTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATC AGATGCTAAAGCCTATGACACAGAGGTACATAATGTCTGGGCCACACATGCCTG TGTACCCACAGACCCTAACCCACAAGAAATAGTATTGGAAAATGTGACAGAAAA TTTTAACATGTGGAAAAATAACATGGTAGAACAGATGCATGAGGATATAATCAG TTTATGGGATCAAAGTCTAAAGCCATGTGTAAAGTTAACCCCACTCTGTGTTACT CTACATTGCACTAATTTGAAGAATGCTACTAATACCAAGAGTAGTAATTGGAAAG AGATGGACAGAGGAGAAATAAAAAATTGCTCTTTCAAGGTCACCACAAGCATAA GAAATAAGATGCAGAAAGAATATGCACTTTTTTATAAACTTGATGTAGTACCAAT AGATAATGATAATACAAGCTATAAATTGATAAATTGTAACACCTCAGTCATTACA CAGGCCTGTCCAAAGGTATCCTTTGAACCAATTCCCATACATTATTGTGCCCCGG CTGGTTTTGCGATTCTAAAGTGTAATGATAAGAAGTTCAATGGATCAGGACCATG TACAAATGTCAGCACAGTACAATGTACACATGGAATTAGGCCAGTAGTGTCAAC TCAATTGCTGTTAAATGGCAGTCTAGCAGAAGAAGGGGTAGTAATTAGATCTGA AAATTTCACAGACAATGCTAAAACTATAATAGTACAGCTGAAGGAATCTGTAGA AATTAATTGTACAAGACCTAACAATAATACAAGAAAAAGTATAACTATAGGACC GGGGAGAGCATTTTATGCAACAGGAGACATAATAGGAGATATAAGACAAGCACA TTGTAACATTAGTGGAGAAAAATGGAATAACACTTTAAAACAGATAGTTACAAA ATTACAAGCACAATTTGGGAATAAAACAATAGTCTTTAAGCAATCCTCAGGAGG GGACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGT AATTCAACACAGCTTTTTAATAGTACTTGGAATAATACTATAGGGCCAAATAACA CTAATGGAACTATCACACTCCCATGCAGAATAAAACAAATTATAAACAGGTGGC AGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGAGGACAAATTAGATGCT CATCAAATATTACAGGACTGCTATTAACAAGAGATGGTGGTAAAGAGATCAGTA ACACCACCGAGATCTTCAGACCTGGAGGTGGAGATATGAGGGACAATTGGAGAA GTGAATTATATAAATATAAAGTAGTAAAAATTGAGCCATTAGGAGTAGCACCCA CCAAGGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCTAGCCACCATCAC CATCACCATTGA (SEQ ID NO :12)

H chain secreted product IgG4H (underline), flexible linker {bold italics), pl20 (bold underline) from SF162, a clade B strain

QVTLKESGPGILQPSOTLSLTCSFSGFSLSTSGMGLSWIRQPSG GLEWLAHIYWDDD KRYNPSL SRLTISKDTSSNOVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVES YGPP CPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSOEDPEVQFNWYVDGVE VHNAKTKPREEOFNSTYRVVSVLTVLHODWLNGKEYKCKVSNKGLPSSIEKTISKAK GQPREPQVYTLPPSOEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN YKTTPPV LDSDGSFFLYSRLTVDKSRWQBGNVFSCSVMHEALHNHYTOKSLSLSLGKASQ77 NTIS VTPTNNSTPTNNSNPKPNPA S VEKLW VT V Y YG VP VWKE ATTTLFC ASP AKA YDTEVHNVWATHACVPTDPNPOEIVLENVTENFNMWKNNMVEQMHEDIISLW DOSLKPCVKLTPLCVTLHCTNLKNATNTKSSNWKEMDRGEIKNCSFKVTTSIRN MOKEYALFYKLDVVPIDNDNTSYKLINCNTSVITOACP VSFEPIPIHYCAPAG FAILKCNDKKFNGSGPCTNVSTVOCTHGIRPVVSTQLLLNGSLAEEGVVIRSENF TDNAKTHVQL ESVEINCTRPNNNTRKSITIGPGRAFYATGDriGDIROAHCNISG EKWNNTLKOIVTKLOAQFGNKTIVF OSSGGDPEIVMHSFNCGGEFFYCNSTQL FNSTWNNTIGPNNTNGTITLPCRIKOIINRWQEVGKAMYAPPIRGOIRCSSNITGL LLTRDGGKEISNTTEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRR VVQRE RASHHHHHH (SEQ ID NO :13) C1776 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-VirafenvHIV-gp41-S-del-6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTGCAGTGACGCTAGGAGCTATGT TCCTTGGGTTCTTGGGAGCAGCAGGAAGCACTATGGGCGCAGCGTCACTGACGCT GACGGTACAGGCCAGACAATTATTGTCTGGTATAGTGCAACAGCAGAACAATTT GCTGAGAGCTATTGAGGCGCAACAGCATCTGTTGCAACTCACAGTCTGGGGCATC AAGCAGCTCCAGGCAAGAGTCCTGGCTGTGGAAAGATACCTAAAGGATCAACAG CTCCTAGGGATTTGGGGTTGCTCTGGAAAACTCATTTGCACCACTGCTGTGCCTT GGAATGCTAGTTGGAGTAATAAATCTCTGGATCAGATTTGGAATAACATGACCTG GATGGAGTGGGAGAGAGAAATTGACAATTACACAAACTTAATATACACCTTAAT TGAAGAATCGCAGAACCAACAAGAAAAGAATGAACAAGAATTATTAGCTAGCCA CCATCACCATCACCATTGA (SEQ ID NO :14) H chain secreted product IgG4H (underline), flexible linker {bold italics), gp41 del (bold underline) from SF162, a clade B strain

OVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGLEWLAHIYWDDD KRYNPSLKSRLTISKDTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP CPPCPAPEFEGGPSVFLFPPKP DTLMISRTPEVTCVVVDVSOEDPEVOFNWYVDGVE VHNA TKPREEQFNSTYRVVSVLTVLHODWLNGKEYKC VSNKGLPSSIEKTISKAK GOPREPQVYTLPPSOEEMTKNQVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPV LDSDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALHNHYTOKSLSLSLGKASOr T NTIS VTPTNNSTPTNNSNPKPNPASAVTLGAMFLGFLGAAGSTMGAASLTLTVQA ROLLSGIVOOONNLLRAIEAOOHLLOLTV GIKOLOARVLAVERYLKDQOLLG IWGCSGKLICTTAVPWNASWSNKSLDOIWNNMTWMEWEREIDNYTNLIYTLIE ESONOOEKNEQELLASHHHHHH (SEQ ID NO :15)

C1784 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gp41-S-6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTGCAGTGACGCTAGGAGCTATGT TCCTTGGGTTCTTGGGAGCAGCAGGAAGCACTATGGGCGCAGCGTCACTGACGCT GACGGTACAGGCCAGACAATTATTGTCTGGTATAGTGCAACAGCAGAACAATTT GCTGAGAGCTATTGAGGCGCAACAGCATCTGTTGCAACTCACAGTCTGGGGCATC AAGCAGCTCCAGGCAAGAGTCCTGGCTGTGGAAAGATACCTAAAGGATCAACAG CTCCTAGGGATTTGGGGTTGCTCTGGAAAACTCATTTGCACCACTGCTGTGCCTT GGAATGCTAGTTGGAGTAATAAATCTCTGGATCAGATTTGGAATAACATGACCTG GATGGAGTGGGAGAGAGAAATTGACAATTACACAAACTTAATATACACCTTAAT TGAAGAATCGCAGAACCAACAAGAAAAGAATGAACAAGAATTATTAGAATTGG ATAAGTGGGCAAGTTTGTGGAATTGGTTTGACATATCAAAATGGCTGTGGTATAT A AAAGCTAGCC ACC ATC ACC ATC ACC ATTG A (SEQ ID NO : 16)

H chain secreted product IgG4H (underline), flexible linker {bold italics), gp41 (bold underline) from SF162, a clade B strain

OVTLKESGPGILQPSOTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGLEWLAHIYWDDD RYNPSLKSRLTISKDTSSNOVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW SGALTS GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP CPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVOFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSN GLPSSIEKTISKA GQPREPQVYTLPPSQEEMTKNQVSLTCLV GFYPSDIAVEWESNGOPENNYKTTPPV LDSDGSFFLYSRLTVDKSRWOEGNVFSCSV HEALHNHYTQKSLSLSLGKASC>r r NTISVTPTNNSTPTNNSNPKPNPASAVThGAMFLGFLGAAGSTMGAASLTLTVOA ROLLSGIVOOONNLLRAIEAOOHLLOLTVWGIKOLOARVLAVERYLKDOQLLG IWGCSGKLICTTAVPWNASWSNKSLDOIVVNNMTWMEWEREIDNYTNLIYTLIE ESONOQEKNEOELLELDKWASEWNWFDISKWLWYIKASHHHHHH (SEQ ID NO :17)

Bold double underlined residues are deleted in the del form of C I 776. C1777 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gp41-Z-6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTGCCGTGGGCATCGGCGCCGTGT TCCTGGGCTTCCTGGGCGCCGCCGGCAGCACCATGGGCGCCGCCAGCATCACCCT GACCGCCCAGGCCCGCCAGGTGCTGAGCGGCATCGTGCAGCAGCAGAGCAACCT GCTGCGCGCCATCGAGGCCCAGCAGCACCTGCTGCAGCTGACCGTGTGGGGCAT CAAGCAGCTGCAGACCCGCGTGCTGGCCATCGAGCGCTACCTGAAGGACCAGCA GCTGCTGGGCCTGTGGGGCTGCAGCGGCAAGCTGATCTGCACCACCGCCGTGCCC TGGAACATCAGCTGGAGCAACAAGAGCAAGACCGACATCTGGGACAACATGACC TGGATGCAGTGGGACCGCGAGATCAGCAACTACACCAACACCATCTACCGCCTG CTGGAGGACAGCCAGAGCCAGCAGGAGCAGAACGAGAAGGACCTGCTGGCCCT GGACAGCTGGAACAACCTGTGGAACTGGTTCGACATCACCAAGTGGCTGTGGTA CATCAAGGCTAGCCACCATCACCATCACCATTGA (SEQ ID NO : 18)

H chain secreted product IgG4H (underline), flexible linker {bold italics), gp41 (bold underline) from HIV-196ZM651 (Clade C)

QVTLKESGPGILOPSOTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGLEWLAHIYWDDD KRYNPSLKSRLTISKDTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP CPPCPAPEFEGGPSVFLFPPKPKDTLM1SRTPEVTCVVVDVSQEDPEVOFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAK GOPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGOPE NYKTTPPV LDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALFlNHYTQKSLSLSLGKASOr r NTISVTPTNNSTPTNNSNPKPNPASAVGIGAVFLGFLGAAGSTMGAASYTLTAQAR OVLSGIVOOOSNLLRAIEAOOHLLQLTVWGIKOLOTRVLAIERYLKDOOLLGL WGCSGKLICTTAVPWNISWSNKSKTDIWDNMTWMQWDREISNYTNTIYRLLED SOSOOEONEKDLLALDSWNNLWNWFDITKWLWYIKASHHHHHH (SEQ ID NO :19)

Double underlined residues are deleted in the del form of CI 785. C1785 [mAnti-DCIR 9E8_H-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gp41-Z-del-6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTGCCGTGGGCATCGGCGCCGTGT TCCTGGGCTTCCTGGGCGCCGCCGGCAGCACCATGGGCGCCGCCAGCATCACCCT GACCGCCCAGGCCCGCCAGGTGCTGAGCGGCATCGTGCAGCAGCAGAGCAACCT GCTGCGCGCCATCGAGGCCCAGCAGCACCTGCTGCAGCTGACCGTGTGGGGCAT CAAGCAGCTGCAGACCCGCGTGCTGGCCATCGAGCGCTACCTGAAGGACCAGCA GCTGCTGGGCCTGTGGGGCTGCAGCGGCAAGCTGATCTGCACCACCGCCGTGCCC TGGAACATCAGCTGGAGCAACAAGAGCAAGACCGACATCTGGGACAACATGACC TGGATGCAGTGGGACCGCGAGATCAGCAACTACACCAACACCATCTACCGCCTG CTGGAGGACAGCCAGAGCCAGCAGGAGCAGAACGAGAAGGACCTGCTGGCTAG CCACCATCACCATCACCATTGA (SEQ ID NO :20) H chain secreted product IgG4H( mderline), flexible linktr(bold italics), gp41 del (bold underline) from HIV-196ZM651 (Clade C)

OVTLKESGPGILOPSQTLSLTCSFSGFSLSTSGMGLSWIROPSGKGLEWLAHIYWDDD KRYNPSLKSRLTIS DTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP CPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSOEDPEVQFNWYVDGVE VHNAKTKPREEOFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTIS AK GOPREPOVYTLPPSOEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALHNHYTOKSLSLSLGKASOr r NTISVTPTNNSTPTNNSNPKPNPASAVG1GAVFLG¥LGAAGSTMGAASITL,TAQAR OVLSGIVOOOSNLLRAIEAOOHLLOLTVWGIKOLOTRVLAIERYLKDOQLLGL WGCSGKLICTTAVPWNISWSNKSKTDIWDNMTWMQWDREISNYTNTIYRLLED SOSOQEQNEKDLLASHHHHHH (SEQ ID NO :21)

C1778 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl20-Z-6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTC AGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTAACCTGTGGGTGACCGTGTACT ACGGCGTGCCCGTGTGGAAGGAGGCCAAGACCACCCTGTTCTGCGCCAGCGACG CCAAGAGCTACGAGAAGGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGC CCACCGACCCCAACCCCCAGGAGATCGTGCTGGGCAACGTGACCGAGAACTTCA ACATGTGGAAGAACGACATGGTGGACCAGATGCACGAGGACATCATCAGCCTGT GGGACCAGAGCCTGAAGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGA ACTGCACCGAGGTGAACGTGACCCGCAACGTGAACAACAGCGTGGTGAACAACA CCACCAACGTGAACAACAGCATGAACGGCGACATGAAGAACTGCAGCTTCAACA TCACCACCGAGCTGAAGGACAAGAAGAAGAACGTGTACGCCCTGTTCTACAAGC TGGACATCGTGAGCCTGAACGAGACCGACGACAGCGAGACCGGCAACAGCAGC AAGTACTACCGCCTGATCAACTGCAACACCAGCGCCCTGACCCAGGCCTGCCCCA AGGTGAGCTTCGACCCCATCCCCATCCACTACTGCGCCCCCGCCGGCTACGCCAT CCTGAAGTGCAACAACAAGACCTTCAACGGCACCGGCCCCTGCCACAACGTGAG CACCGTGCAGTGCACCCACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCT GAACGGCAGCCTGGCCGAGGAGGGCATCATCATCCGCAGCGAGAACCTGACCAA CAACGTCAAGACCATCATCGTGCACCTGAACCGCAGCATCGAGATCGTGTGCGT GCGCCCCAACAACAACACCCGCCAGAGCATCCGCATCGGCCCCGGCCAGACCTT CTACGCCACCGGCGACATCATCGGCGACATCCGCCAGGCCCACTGCAACATCAG CCGCACCAACTGGACCAAGACCCTGCGCGAGGTGCGCAACAAGCTGCGCGAGCA CTTCCCCAACAAGAACATCACCTTCAAGCCCAGCAGCGGCGGCGACCTGGAGAT CACCACCCACAGCTTCAACTGCCGCGGCGAGTTCTTCTACTGCAACACCAGCGGC CTGTTCAGCATCAACTACACCGAGAACAACACCGACGGCACCCCCATCACCCTGC CCTGCCGCATCCGCCAGATCATCAACATGTGGCAGGAGGTGGGCCGCGCCATGT ACGCCCCCCCCATCGAGGGCAACATCGCCTGCAAGAGCGACATCACCGGCCTGC TGCTGGTGCGCGACGGCGGCAGCACCAACGACAGCACCAACAACAACACCGAGA TCTTCCGCCCCGCCGGCGGCGACATGCGCGACAACTGGCGCAGCGAGCTGTACA AGTACAAGGTGGTGGAGATCAAGCCCCTGGGCATCGCCCCCACCGAGGCCAAGC GCCGCGTGGTGGAGCGCGAGAAGCGCGCTAGCCACCATCACCATCACCATTGA

(SEQ ID NO :22) H chain secreted product IgG4H(underline), flexible \mker(bold italics), gpl20 (bold underline) from HIV-196ZM651 (Clade C)

QVTL ESGPGILQPSOTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGLEWLAHIYWDDD KRYNPSLKSRLTISKDTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVPSSSLGT TYTCNVDHKPSNTKVDKRVESKYGPP CPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLHODWLNGKEYKCKVSNKGLPSSIEKTISKAK GQPREPQVYTLPPSQEEMT NOVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALHNHYTOKSLSLSLGKAS(>T r NTJSVTPTNNSTPTNNSNPKPNPASN SYYTYYYGYYYyVKEAKTThFCASOAKSYE KEVHNVWATHACVPTDPNPOEIVLGNVTENFNMWKNDMVDOMHEDIISLWDQ SLKPCVKLTPLCVTLNCTEVNVTRNVNNSVVNNTTNVNNSMNGDMKNCSFNITT ELKDKK NVYALFYKLDIVSLNETDDSETGNSSKYYRLINCNTSALTQACPKVSF DPIPIHYCAPAGYAILKCNNKTFNGTGPCHNVSTVOCTHGI PVVSTOLLLNGSL AEEGHIRSENLTNNVKTIIVHLNRSIEIVCVRPNNNTROSIRIGPGOTFYATGDIIG DIRQAHCNISRTNWTKTLREVRNKLREHFPNKNITFKPSSGGDLEITTHSFNCRG EFFYCNTSGLFSINYTENNTDGTPITLPCRIROIINMWQEVGRAMYAPPIEGNIAC KSDITGLLLVRDGGSTNDSTNNNTEIFRPAGGDMRDNWRSELYKYKVVEIKPLG IAPTEAKRRVVEREKRASHHHHHH(SEQ ID NO :23)

C1786 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-Z-6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCFACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTAACCTGTGGGTGACCGTGTACT ACGGCGTGCCCGTGTGGAAGGAGGCCAAGACCACCCTGTTCTGCGCCAGCGACG CCAAGAGCTACGAGAAGGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGC CCACCGACCCCAACCCCCAGGAGATCGTGCTGGGCAACGTGACCGAGAACTTCA ACATGTGGAAGAACGACATGGTGGACCAGATGCACGAGGACATCATCAGCCTGT GGGACCAGAGCCTGAAGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGA ACTGCACCGAGGTGAACGTGACCCGCAACGTGAACAACAGCGTGGTGAACAACA CCACCAACGTGAACAACAGCATGAACGGCGACATGAAGAACTGCAGCTTCAACA TCACCACCGAGCTGAAGGACAAGAAGAAGAACGTGTACGCCCTGTTCTACAAGC TGGACATCGTGAGCCTGAACGAGACCGACGACAGCGAGACCGGCAACAGCAGC AAGTACTACCGCCTGATCAACTGCAACACCAGCGCCCTGACCCAGGCCTGCCCCA AGGTGAGCTTCGACCCCATCCCCATCCACTACTGCGCCCCCGCCGGCTACGCCAT CCTGAAGTGCAACAACAAGACCTTCAACGGCACCGGCCCCTGCCACAACGTGAG CACCGTGCAGTGCACCCACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCT GAACGGCAGCCTGGCCGAGGAGGGCATCATCATCCGCAGCGAGAACCTGACCAA CAACGTCAAGACCATCATCGTGCACCTGAACCGCAGCATCGAGATCGTGTGCGT GCGCCCCAACAACAACACCCGCCAGAGCATCCGCATCGGCCCCGGCCAGACCTT CTACGCCACCGGCGACATCATCGGCGACATCCGCCAGGCCCACTGCAACATCAG CCGCACCAACTGGACCAAGACCCTGCGCGAGGTGCGCAACAAGCTGCGCGAGCA CTTCCCCAACAAGAACATCACCTTCAAGCCCAGCAGCGGCGGCGACCTGGAGAT CACCACCCACAGCTTCAACTGCCGCGGCGAGTTCTTCTACTGCAACACCAGCGGC CTGTTCAGCATCAACTACACCGAGAACAACACCGACGGCACCCCCATCACCCTGC CCTGCCGCATCCGCCAGATCATCAACATGTGGCAGGAGGTGGGCCGCGCCATGT ACGCCCCCCCCATCGAGGGCAACATCGCCTGCAAGAGCGACATCACCGGCCTGC TGCTGGTGCGCGACGGCGGCAGCACCAACGACAGCACCAACAACAACACCGAGA TCTTCCGCCCCGCCGGCGGCGACATGCGCGACAACTGGCGCAGCGAGCTGTACA AGTACAAGGTGGTGGAGATCAAGCCCCTGGGCATCGCCCCCACCGAGGCCAAGC GCCGCGTGGTGGAGCGCGAGAAGCGCGCCGTGGGCATCGGCGCCGTGTTCCTGG GCTTCCTGGGCGCCGCCGGCAGCACCATGGGCGCCGCCAGCATCACCCTGACCG CCCAGGCCCGCCAGGTGCTGAGCGGCATCGTGCAGCAGCAGAGCAACCTGCTGC GCGCCATCGAGGCCCAGCAGCACCTGCTGCAGCTGACCGTGTGGGGCATCAAGC AGCTGCAGACCCGCGTGCTGGCCATCGAGCGCTACCTGAAGGACCAGCAGCTGC TGGGCCTGTGGGGCTGCAGCGGCAAGCTGATCTGCACCACCGCCGTGCCCTGGA ACATCAGCTGGAGCAACAAGAGCAAGACCGACATCTGGGACAACATGACCTGGA TGCAGTGGGACCGCGAGATCAGCAACTACACCAACACCATCTACCGCCTGCTGG AGGACAGCCAGAGCCAGCAGGAGCAGAACGAGAAGGACCTGCTGGCCCTGGAC AGCTGGAACAACCTGTGGAACTGGTTCGACATCACCAAGTGGCTGTGGTACATC AAGGCTAGCCACCATCACCATCACCATTGA(SEQ ID NO :24)

H chain secreted product IgG4H(underline), flexible linker(bold italics), gpl40 (bold underline) from HIV-196ZM651 (Clade C)

QVTLKESGPGILQPSOTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGLEWLAHIYWDDD RYNPSLKSRLTISKDTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLV DYFPEPVTVSWNSGALTS GVFITFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP CPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSOEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAK GOPREPOVYTLPPSOEEMTKNQVSLTCLVKGFYPSDIAVEWESNGOPEN YKTTPPV LDSDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALHNHYTOKSLSLSLGKASgJfr NTIS VTPTNNSTPTNNSNPKPNPASNLy/VTVYYGVPVWKEAKTTLFCASOAKSYE KEVHNVWATHACVPTDPNPQEIVLGNVTENFNMWKNDMVDOMHEDHSLWDO SLKPCVKLTPLCVTLNCTEVNVTRNVNNSVVNNTTNVNNSMNGDMKNCSFNITT ELKDKKKNVYALFYKLDIVSLNETDDSETGNSSKYYRLINCNTSALTQACPKVSF DPIPIHYCAPAGYAILKCNNKTFNGTGPCHNVSTVOCTHGIKPVVSTOLLLNGSL AEEGIIIRSENLTNNVKTnVHLNRSIEIVCVRPNNNTROSIRIGPGOTFYATGDIIG DIROAHCNISRTNWTKTLREVRNKLREHFPNKNITFKPSSGGDLEITTHSFNCRG EFFYCNTSGLFSINYTENNTDGTPITLPCRIROIINMWQEVGRAMYAPPIEGNIAC KSDITGLLLVRDGGSTNDSTNNNTEIFRPAGGDMRDNWRSELYKYKVVEIKPLG IAPTEAKRRVVEREKRAVGIGAVFLGFLGAAGSTMGAASITLTAQAROVLSGIV OOOSNLLRAIEAOOHLLOLTVWGIKOLQTRVLAIERYLKDOOLLGLWGCSGKL ICTTAVPWNISWSNKSKTDIWDNMTWMOWDREISNYTNTIYRLLEDSOSOOEO NEKDLLALDSWN LWNWFDITKWLWYIKASHHHHHH(SEO ID NO :25)

Double Underlined residues are removed in the del form of C1787.

C1787 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-Z-del-6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTAACCTGTGGGTGACCGTGTACT ACGGCGTGCCCGTGTGGAAGGAGGCCAAGACCACCCTGTTCTGCGCCAGCGACG CCAAGAGCTACGAGAAGGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGC CCACCGACCCCAACCCCCAGGAGATCGTGCTGGGCAACGTGACCGAGAACTTCA AC ATGTGGAAGAACGACATGGTGGACCAGATGCACGAGGACATCATCAGCCTGT GGGACCAGAGCCTGAAGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGA ACTGCACCGAGGTGAACGTGACCCGCAACGTGAACAACAGCGTGGTGAACAACA CCACCAACGTGAACAACAGCATGAACGGCGACATGAAGAACTGCAGCTTCAACA TCACCACCGAGCTGAAGGACAAGAAGAAGAACGTGTACGCCCTGTTCTACAAGC TGGACATCGTGAGCCTGAACGAGACCGACGACAGCGAGACCGGCAACAGCAGC AAGTACTACCGCCTGATCAACTGCAACACCAGCGCCCTGACCCAGGCCTGCCCCA AGGTGAGCTTCGACCCCATCCCCATCCACTACTGCGCCCCCGCCGGCTACGCCAT CCTGAAGTGCAACAACAAGACCTTCAACGGCACCGGCCCCTGCCACAACGTGAG CACCGTGCAGTGCACCCACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCT GAACGGCAGCCTGGCCGAGGAGGGCATCATCATCCGCAGCGAGAACCTGACCAA CAACGTCAAGACCATCATCGTGCACCTGAACCGCAGCATCGAGATCGTGTGCGT GCGCCCCAACAACAACACCCGCCAGAGCATCCGCATCGGCCCCGGCCAGACCTT CTACGCCACCGGCGACATCATCGGCGACATCCGCCAGGGCCACTGCAACATCAG CCGCACCAACTGGACCAAGACCCTGCGCGAGGTGCGCAACAAGCTGCGCGAGCA CTTCCCCAACAAGAACATCACCTTCAAGCCCAGCAGCGGCGGCGACCTGGAGAT CACCACCCACAGCTTCAACTGCCGCGGCGAGTTCTTCTACTGCAACACCAGCGGC CTGTTCAGCATCAACTACACCGAGAACAACACCGACGGCACCCCCATCACCCTGC CCTGCCGCATCCGCCAGATCATCAACATGTGGCAGGAGGTGGGCCGCGCCATGT ACGCCCCCCCCATCGAGGGCAACATCGCCTGCAAGAGCGACATCACCGGCCTGC TGCTGGTGCGCGACGGCGGCAGCACCAACGACAGCACCAACAACAACACCGAGA TCTTCCGCCCCGCCGGCGGCGACATGCGCGACAACTGGCGCAGCGAGCTGTACA AGTACAAGGTGGTGGAGATCAAGCCCCTGGGCATCGCCCCCACCGAGGCCAAGC GCCGCGTGGTGGAGCGCGAGAAGCGCGCCGTGGGCATCGGCGCCGTGTTCCTGG GCTTCCTGGGCGCCGCCGGCAGCACCATGGGCGCCGCCAGCATCACCCTGACCG CCCAGGCCCGCCAGGTGCTGAGCGGCATCGTGCAGCAGCAGAGCAACCTGCTGC GCGCCATCGAGGCCCAGCAGCACCTGCTGCAGCTGACCGTGTGGGGCATCAAGC AGCTGCAGACCCGCGTGCTGGCCATCGAGCGCTACCTGAAGGACCAGCAGCTGC TGGGCCTGTGGGGCTGCAGCGGCAAGCTGATCTGCACCACCGCCGTGCCCTGGA ACATCAGCTGGAGCAACAAGAGCAAGACCGACATCTGGGACAACATGACCTGGA TGCAGTGGGACCGCGAGATCAGCAACTACACCAACACCATCTACCGCCTGCTGG AGGACAGCCAGAGCCAGCAGGAGCAGAACGAGAAGGACCTGCTGGCTAGCCAC CATCACCATCACCATTGA(SEQ ID NO :26) H chain secreted product IgG4H(underiine), flexible Iinker(Z>o/rf italics), gpl40 del (bold underline) from HIV-196ZM651 (Clade C)

QVTLKESGPGILQPSOTLSLTCSFSGFSLSTSGMGLSWIROPSGKGLEWLAHIYWDDD RYNPSLKSRLTISKDTSSNOVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP CPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVE VHNAKTKPREEOFNSTYRVVSVLTVLHQDWLNGKEYKC VSNKGLPSSIEKTISKAK GQPREPQVYTLPPSOEEMTKNOVSLTCLVKGFYPSDIAVEWESNGQPEN YKTTPPV LDSDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALHNHYTQ SLSLSLGKASOr T NTISVTPTNNSTPTNNSNPKPNPASNLV/VT\YYG\P\\VKEAKJTI,FCASOAKSYE KEVHNVWATHACVPTDPNPQEIVLGNVTENFNMWKNDMVDOMHEDIISLWDO SLKPCVKLTPLCVTLNCTEVNVTRNVNNSVVNNTTNVNNSMNGDMKNCSFNITT ELKDKKKNVYALFYKLDIVSLNETDDSETGNSSKYYRLINCNTSALTQACPKVSF DPIPIHYCAPAGYAILKCNNKTFNGTGPCHNVSTVOCTHGIKPVVSTOLLLNGSL AEEGIIIRSENLTNNVKTIIVHLNRSIEIVCVRPNNNTROSIRIGPGQTFYATGDHG DIROAHCNISRTNWTKTLREVRNKLREHFPNKNITFKPSSGGDLEITTHSFNCRG EFFYCNTSGLFSINYTENNTDGTPITLPCRIROIINMWOEVGRAMYAPPIEGNIAC KSDITGLLLVRDGGSTNDSTNNNTEIFRPAGGDMRDNWRSELYKYKVVEIKPLG IAPTEAKRRVVEREKRAVGIGAVFLGFLGAAGSTMGAASITLTAOARQVLSGIV OOOSNLLRAIEAOOHLLQLTVWGIKOLOTRVLAIERYLKDOQLLGLWGCSGKL ICTTAVPWNISWSNKSKTDIWDNMTWMQWDREISNYTNTIYRLLEDSOSQOEO NEKDLLASHHHHHH(SEQ ID NO :27)

C2424 [hAnti-CD40VH3-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-Z-6xHis] ATGGGTTGGAGCCTCATCTTGCTCTTCCTTGTCGCTGTTGCTACGCGTGTCCACTC CGAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCCGGAGGGTCCCT GAAACTCTCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGG TTCGCCAGGCCCCAGGCAAGGGCCTGGAGTGGGTCGCATACATTAATTCTGGTGG TGGTAGCACCTATTATCCAGACACTGTAAAGGGCCGATTCACCATCTCCAGAGAC AATGCCAAGAACACCCTGTACCTGCAAATGAACAGCCTGAGGGCCGAGGACACA GCCGTGTATTACTGTGCAAGACGGGGGTTACCGTTCCATGCTATGGACTATTGGG GTCAAGGAACCCTGGTCACCGTCTCCTCAGCCAAAACGAAGGGCCCATCCGTCTT CCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGC CTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTC CCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACAC CTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTC CAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACC ATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACC CCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAG TTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGG GAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACC AGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCC CGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCAC AGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCC TGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGA GCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCG ACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGG AGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACAC ACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTCAGACCCCCACCAACACC ATCAGCGTGACCCCCACCAACAACAGCACCCCCACCAACAACAGCAACCCCAAG CCCAACCCCGCTAGTAACCTGTGGGTGACCGTGTACTACGGCGTGCCCGTGTGGA AGGAGGCCAAGACCACCCTGTTCTGCGCCAGCGACGCCAAGAGCTACGAGAAGG AGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGCCCACCGACCCCAACCCCC AGGAGATCGTGCTGGGCAACGTGACCGAGAACTTCAACATGTGGAAGAACGACA TGGTGGACCAGATGCACGAGGACATCATCAGCCTGTGGGACCAGAGCCTGAAGC CCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGAACTGCACCGAGGTGAACGT GACCCGCAACGTGAACAACAGCGTGGTGAACAACACCACCAACGTGAACAACAG CATGAACGGCGACATGAAGAACTGCAGCTTCAACATCACCACCGAGCTGAAGGA CAAGAAGAAGAACGTGTACGCCCTGTTCTACAAGCTGGACATCGTGAGCCTGAA CGAGACCGACGACAGCGAGACCGGCAACAGCAGCAAGTACTACCGCCTGATCAA CTGCAACACCAGCGCCCTGACCCAGGCCTGCCCCAAGGTGAGCTTCGACCCCATC CCCATCCACTACTGCGCCCCCGCCGGCTACGCCATCCTGAAGTGCAACAACAAGA CCTTCAACGGCACCGGCCCCTGCCACAACGTGAGCACCGTGCAGTGCACCCACG GCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCTGAACGGCAGCCTGGCCGAGG AGGGCATCATCATCCGCAGCGAGAACCTGACCAACAACGTCAAGACCATCATCG TGCACCTGAACCGCAGCATCGAGATCGTGTGCGTGCGCCCCAACAACAACACCC GCCAGAGCATCCGCATCGGCCCCGGCCAGACCTTCTACGCCACCGGCGACATCAT CGGCGACATCCGCCAGGCCCACTGCAACATCAGCCGCACCAACTGGACCAAGAC CCTGCGCGAGGTGCGCAACAAGCTGCGCGAGCACTTCCCCAACAAGAACATCAC CTTCAAGCCCAGCAGCGGCGGCGACCTGGAGATCACCACCCACAGCTTCAACTG CCGCGGCGAGTTCTTCTACTGCAACACCAGCGGCCTGTTCAGCATCAACTACACC GAGAACAACACCGACGGCACCCCCATCACCCTGCCCTGCCGCATCCGCCAGATC ATCAACATGTGGCAGGAGGTGGGCCGCGCCATGTACGCCCCCCCCATCGAGGGC AACATCGCCTGCAAGAGCGACATCACCGGCCTGCTGCTGGTGCGCGACGGCGGC AGCACCAACGACAGCACCAACAACAACACCGAGATCTTCCGCCCCGCCGGCGGC GACATGCGCGACAACTGGCGCAGCGAGCTGTACAAGTACAAGGTGGTGGAGATC AAGCCCCTGGGCATCGCCCCCACCGAGGCCAAGCGCCGCGTGGTGGAGCGCGAG AAGCGCGCCGTGGGCATCGGCGCCGTGTTCCTGGGCTTCCTGGGCGCCGCCGGCA GCACCATGGGCGCCGCCAGCATCACCCTGACCGCCCAGGCCCGCCAGGTGCTGA GCGGCATCGTGCAGCAGCAGAGCAACCTGCTGCGCGCCATCGAGGCCCAGCAGC ACCTGCTGCAGCTGACCGTGTGGGGCATCAAGCAGCTGCAGACCCGCGTGCTGG CCATCGAGCGCTACCTGAAGGACCAGCAGCTGCTGGGCCTGTGGGGCTGCAGCG GCAAGCTGATCTGCACCACCGCCGTGCCCTGGAACATCAGCTGGAGCAACAAGA GCAAGACCGACATCTGGGACAACATGACCTGGATGCAGTGGGACCGCGAGATCA GCAACTACACCAACACCATCTACCGCCTGCTGGAGGACAGCCAGAGCCAGCAGG AGCAGAACGAGAAGGACCTGCTGGCCCTGGACAGCTGGAACAACCTGTGGAACT GGTTCGACATCACCAAGTGGCTGTGGTACATCAAGGCTAGCCACCATCACCATCA CCATTGA(SEQ ID NO :28)

H chain secreted product IgG4H(underline), flexible linker(bold italics), gpl40 (bold underline) from HIV-196ZM651 (Clade C) EVQLVESGGGLVQPGGSLKLSCATSGFTFSDYYMYWVRQAPGKGLEWVAYINSGG GSTYYPDTVKGRFTISRDNAKNTLYLOM SLRAEDTAVYYCARRGLPFHAMDYWG QGTLVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLOSSGLYSLSSVVTVPSSSLGT TYTCNVDHKPSNTKVD RVESKYGPPC PPCPAPEFEGGPSVFLFPP P DTLMISRTPEVTCWVDVSOEDPEVOFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLHODWLNGKEYKCKVSNKGLPSSIEKTISKAK GOPREPOVYTLPPSOEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN YKTTPPV LDSDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALHNHYTOKSLSLSLGKAS >7Pr NTISVTPTNNSTPTNNSNPKPNPASNLy/VTVYYGVVVWKEAKTTLFCASOAKSYE EVHNVWATHACVPTDPNPOEIVLGNVTENFNMWKNDMVDOMHEDIISLWDQ SLKPCVKLTPLCVTLNCTEVNVTRNVNNSVVNNTTNVNNSMNGDMKNCSFNITT ELKDKKKNVYALFYKLDIVSLNETDDSETGNSSKYYRLINCNTSALTOACPKVSF DPIPIHYCAPAGYAILKCNNKTFNGTGPCHNVSTVOCTHGIKPVVSTQLLLNGSL AEEGIIIRSENLTNNVKTIIVHLNRSIEIVCVRPNNNTROSIRIGPGOTFYATGDIIG DIROAHCNISRTNWTKTLREVRN LREHFPNKNITFKPSSGGDLEITTHSFNCRG EFFYCNTSGLFSINYTENNTDGTPITLPCRIROIINMWQEVGRAMYAPPIEGNIAC KSDITGLLLVRDGGSTNDSTNNNTEIFRPAGGDMRDNWRSELYKYKVVEIKPLG IAPTEAKRRVVERE RAVGIGAVFLGFLGAAGSTMGAASITLTAOAROVLSGIV OOOSNLLRAIEAOQHLLQLTVWGIKOLOTRVLAIERYLKDOOLLGLWGCSG L ICTTAVPWNISWSN SKTDIWDNMTWMOWDREISNYTNTIYRLLEDSOSOOEQ NEKDLLALDSWNNLWNWFDITKWLWYIKASHHHHHH(SEO ID NO :29)

C2270 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-C-6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTAACCTGTGGGTGACCGTGTACT ACGGCGTGCCCGTGTGGAAGGGCGCCACCACCACCCTGTTCTGCGCCAGCGACG CCAAGGCCTACGACACCGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGC CCGCCGACCCCAACCCCCAGGAGATGGTGCTGGAGAACGTGACCGAGAACTTCA ACATGTGGAAGAACGAGATGGTGAACCAGATGCAGGAGGACGTCATCAGCCTGT GGGACCAGAGCCTGAAGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGG AGTGCAGGAACGTGAGCAGCAACAGCAACGACACCTACCACGAGACCTACCACG AGAGCATGAAGGAGATGAAGAACTGCAGCTTCAACGCCACCACCGTGGTGAGGG ACAGGAAGCAGACCGTGTACGCCCTGTTCTACAGGCTGGACATCGTGCCCCTGAC CAAGAAGAACTACAGCGAGAACAGCAGCGAGTACTACAGGCTGATCAACTGCAA CACCAGCGCCATCACCCAGGCCTGCCCCAAGGTGACCTTCGACCCCATCCCCATC CACTACTGCACCCCCGCCGGCTACGCCATCCTGAAGTGCAACGACAAGATCTTCA ACGGCACCGGCCCCTGCCACAACGTGAGCACCGTGCAGTGCACCCACGGCATCA AGCCCGTGGTGAGCACCCAGCTGCTGCTGAACGGCAGCCTGGCCGAGGGCGAGA TCATCATCAGGAGCGAGAACCTGACCAACAACGTGAAAACCATCATCGTGCACC TGAACCAGAGCGTGGAGATCGTGTGCACCAGGCCCGGCAACAACACCAGGAAGA GCATCAGGATCGGCCCCGGCCAGACCTTCTACGCCACCGGCGACATCATCGGCG ACATCAGGCAGGCCCACTGCAACATCAGCGAGGACAAGTGGAACGAGACCCTGC AGAGGGTGAGCAAGAAGCTTGCCGAGCACTTCCAGAACAAGACCATCAAGTTCG CCAGCAGCAGCGGCGGCGACCTGGAGGTGACCACCCACAGCTTCAACTGCAGGG GCGAGTTCTTCTACTGCAACACCAGCGGCCTGTTCAACGGCGCCTACACCCCCAA CGGCACCAAGAGCAACAGCAGCAGCATCATCACCATCCCCTGCAGGATCAAGCA GATCATCAACATGTGGCAGGAGGTGGGCAGGGCCATGTACGCCCCTCCCATCAA GGGCAACATCACCTGCAAGAGCAACATCACCGGCCTGCTGCTGGTGAGGGACGG CGGCACCGAGCCCAACGACACCGAGACCTTCAGGCCCGGCGGCGGCGACATGAG GAACAACTGGAGGAGCGAGCTGTACAAGTACAAGGTGGTGGAGATCAAGCCCCT GGGCGTGGCCCCCACCACCACCAAGAGGAGGGTGGTGGAGAGGGAGAAGAGCG CCGTGGGCATCGGCGCCGTGTTCCTGGGCTTCCTGGGCGTGGCCGGCAGCACCAT GGGCGCCGCCAGCATCACCCTGACCGTGCAGGCCAGGCAGCTGCTGAGCGGCAT CGTGCAGCAGCAGAGCAACCTGCTGAGGGCCATCGAGGCCCAGCAGCACCTGCT GCAGCTGACCGTGTGGGGCATCAAGCAGCTGCAGACCAGGGTGCTGGCCATCGA GAGGTACCTGAAGGACCAGCAGCTGCTGGGCATCTGGGGCTGCAGCGGCAAGCT GATCTGCACCACCGCCGTGCCCTGGAACAGCAGCTGGAGCAACAAGAGCCAGAA GGAGATCTGGGACAACATGACCTGGATGCAGTGGGACAAGGAGATCAGCAACTA CACCAACACCGTGTACAGGCTGCTGGAGGAGAGCCAGAACCAGCAGGAGAGGA ACGAGAAGGACCTGCTGGCCCTGGACAGCCATCACCATCACCATCACTGA(SEQ ID NO :30)

H chain secreted product IgG4H(underline), flexible linker(Ao/i/ italics), gpl40 (bold underline) from HIV-1 CN54 (Clade C)

OVTLKESGPGILOPSOTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGLEWLAHIYWDDD KRYNPSLKSRLTISKDTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS G VHTFP A V LOS S GLYS LSS V VTVPS S SLGTKT YTCN VDHKP SNTKVDKRVESKYGPP CPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSOEDPEVOFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLHODWLNGKEYKCKVSNKGLPSSIEKTISKAK GOPREPOVYTLPPSOEEMTKNQVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPV LDSDGSFFLYSRLTVD SRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKASOrPr NTISVTPTNNSTPTNNSNPKPNPASNLWVTVYYGVPYWKGATTTLFCASOAKAYO TEVHNVWATHACVPADPNPOEMVLENVTENFNMWKNEMVNOMOEDVISLWD OSLKPCVKLTPLCVTLECRNVSSNSNDTYHETYHESMKEMKNCSFNATTVVRD RKOTVYALFYRLDIVPLTK NYSEIVSSEYYRLINCNTSAITOACPKVTFDPIPIHY CTPAGYAILKCNDKIFNGTGPCHNVSTVQCTHGIKPVVSTOLLLNGSLAEGEIIIR SENLTNNVKTIIVHLNOSVE1VCTRPGNNTRKSIRIGPGOTFYATGDHGDIRQAH CNISEDKWNETLQRVSKKLAEHFQNKTIKFASSSGGDLEVTTHSFNCRGEFFYC NTSGLFNGAYTPNGTKSNSSSIITIPCRIKOIINMWOEVGRAMYAPPIKGNITCKS NITGLLLVRDGGTEPNDTETFRPGGGDMRNNWRSELYKYKVVEIKPLGVAPTT TKRRVVEREKSAVGIGAVFLGFLGVAGSTMGAASITLTVOAROLLSG1VOOOSN LLRAIEAOOHLLOLTVWGIKOLOTRVLAIERYLKDOQLLGIWGCSGKLICTTAV PWNSSWSNKSQKEIWDNMTWMOWDKEISNYTNTVYRLLEESONOQERNEKDL LALDSHHHHHH(SEQ ID NO :31)

C2272 [hAnti-LOX-lVH3-LV-hIgG4H-C-FIex-vl-ViralenvHIV-gpl40-C-6xHis]

ATGGGTTGGAGCCTCATCTTGCTCTTCCTTGTCGCTGTTGCTACGCGTGTCCACTC CGAGATCCAGCTGGTGCAGAGCGGAAGCGAGCTGAAGAAGCCTGGGGCTTCAGT GAAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGG GTGAGGCAGGCCCCTGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTAC TATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACATTGACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAGCAGTCTGAGATCTGAGGACA CCGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTAGCGCCAAAACGAAGGGCCCATC CGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTG GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACT CTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACC TACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTT GAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGG GACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCG GACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGT CCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCC GCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCT GCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT CAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC TCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGC AGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTA CACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTCAGACCCCCACCAAC ACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCAACAACAGCAACCCC AAGCCCAACCCCGCTAGTAACCTGTGGGTGACCGTGTACTACGGCGTGCCCGTGT GGAAGGGCGCCACCACCACCCTGTTCTGCGCCAGCGACGCCAAGGCCTACGACA CCGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGCCCGCCGACCCCAACC CCCAGGAGATGGTGCTGGAGAACGTGACCGAGAACTTCAACATGTGGAAGAACG AGATGGTGAACCAGATGCAGGAGGACGTCATCAGCCTGTGGGACCAGAGCCTGA AGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGGAGTGCAGGAACGTGA GCAGCAACAGCAACGACACCTACCACGAGACCTACCACGAGAGCATGAAGGAG ATGAAGAACTGCAGCTTCAACGCCACCACCGTGGTGAGGGACAGGAAGCAGACC GTGTACGCCCTGTTCTACAGGCTGGACATCGTGCCCCTGACCAAGAAGAACTACA GCGAGAACAGCAGCGAGTACTACAGGCTGATCAACTGCAACACCAGCGCCATCA CCCAGGCCTGCCCCAAGGTGACCTTCGACCCC ATCCCCATCC ACTACTGCACCCC CGCCGGCTACGCCATCCTGAAGTGCAACGACAAGATCTTCAACGGCACCGGCCC CTGCCACAACGTGAGCACCGTGCAGTGCACCCACGGCATCAAGCCCGTGGTGAG CACCCAGCTGCTGCTGAACGGCAGCCTGGCCGAGGGCGAGATCATCATCAGGAG CGAGAACCTGACCAACAACGTGAAAACCATCATCGTGCACCTGAACCAGAGCGT GGAGATCGTGTGCACCAGGCCCGGCAACAACACCAGGAAGAGCATCAGGATCGG CCCCGGCCAGACCTTCTACGCCACCGGCGACATCATCGGCGACATCAGGCAGGC CCACTGCAACATCAGCGAGGACAAGTGGAACGAGACCCTGCAGAGGGTGAGCA AGAAGCTTGCCGAGCACTTCCAGAACAAGACCATCAAGTTCGCCAGCAGCAGCG GCGGCGACCTGGAGGTGACCACCCACAGCTTCAACTGCAGGGGCGAGTTCTTCT ACTGCAACACCAGCGGCCTGTTCAACGGCGCCTACACCCCCAACGGCACCAAGA GCAACAGCAGCAGCATCATCACCATCCCCTGCAGGATCAAGCAGATCATCAACA TGTGGCAGGAGGTGGGCAGGGCCATGTACGCCCCTCCCATCAAGGGCAACATCA CCTGCAAGAGCAACATCACCGGCCTGCTGCTGGTGAGGGACGGCGGCACCGAGC CCAACGACACCGAGACCTTCAGGCCCGGCGGCGGCGACATGAGGAACAACTGGA GGAGCGAGCTGTACAAGTACAAGGTGGTGGAGATCAAGCCCCTGGGCGTGGCCC CCACCACCACCAAGAGGAGGGTGGTGGAGAGGGAGAAGAGCGCCGTGGGCATC GGCGCCGTGTTCCTGGGCTTCCTGGGCGTGGCCGGCAGCACCATGGGCGCCGCCA GCATCACCCTGACCGTGCAGGCCAGGCAGCTGCTGAGCGGCATCGTGCAGCAGC AGAGCAACCTGCTGAGGGCCATCGAGGCCCAGCAGCACCTGCTGCAGCTGACCG TGTGGGGCATCAAGCAGCTGCAGACCAGGGTGCTGGCCATCGAGAGGTACCTGA AGGACCAGCAGCTGCTGGGCATCTGGGGCTGCAGCGGCAAGCTGATCTGCACCA CCGCCGTGCCCTGGAACAGCAGCTGGAGCAACAAGAGCCAGAAGGAGATCTGGG ACAACATGACCTGGATGCAGTGGGACAAGGAGATCAGCAACTACACCAACACCG TGTACAGGCTGCTGGAGGAGAGCCAGAACCAGCAGGAGAGGAACGAGAAGGAC CTGCTGGCCCTGGACAGCCATCACCATCACCATCACTGA(SEQ ID NO :32)

H chain secreted product IgG4H(underline), flexible \inker(bold italics), gpl40 (bold underline) from HIV-1 CN54 (Clade C)

EIQLVQSGSELKKPGASVKISCKASGYPFTDYIMVWVRQAPGKGLEWIGNISPYYGTT NY LKFKGRATLTVDKSTSTAYMELSSLRSEDTAVYYCARSPNWDGAWFAHWGQG ALVTVSSAKT GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLOSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPP CPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVH NAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQ PREPOVYTLPPSQEEMTKNOVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPVLD SDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALHNHYTQKSLSLSLGKASgr riVr/ SVTPTNNSTPTNNSNPKPNPASNLWVTVYYGVV\VJKGATTTL¥CASOAKAY E VHNVWATHACVPADPNPQEMVLENVTENFNMWKNEMVNOMOEDVISLWDOS LKPCVKLTPLCVTLECRNVSSNSNDTYHETYHESMKEMKNCSFNATTVVRDRK OTVYALFYRLDIVPLTKKNYSENSSEYYRLINCNTSAITQACPKVTFDPIPIHYCT PAGYAILKCNDKIFNGTGPCHNVSTVOCTHGIKPVVSTQLLLNGSLAEGEIIIRSE NLTNNVKTIIVHLNOSVEIVCTRPGNNTRKSIRIGPGOTFYATGDHGDIRQAHCN ISEDKWNETLQRVSKKLAEHFQNKTIKFASSSGGDLEVTTHSFNCRGEFFYCNTS GLFNGAYTPNGTKSNSSSIITIPCRIKOIINMWOEVGRAMYAPPI GNITCKSNIT GLLLVRDGGTEPNDTETFRPGGGDMRNNWRSELYKYKVVEIKPLGVAPTTTKR RVVEREKSAVGIGAVFLGFLGVAGSTMGAASITLTVOAROLLSGIVOOOSNLLR AIEAOOHLLOLTVWGIKOLQTRVLAIERYLKDOOLLGIWGCSGKLICTTAVPW NSSWSNKSOKEIWDNMTWMQWDKEISNYTNTVYRLLEESONOQERNEKDLLA LDSHHHHHHfSEQ ID NO :33)

C2273 [hAnti-LOX-lVH7-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-C-6xHis]

ATGGGTTGGAGCCTCATCTTGCTCTTCCTTGTCGCTGTTGCTACGCGTGTCCACTC CGAGATCCAGCTGGTGCAGAGCGGAAGCGAGCTGAAGAAGCCTGGGGCTTCAGT GAAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGG GTGAAGCAGGCCCATGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTAC TATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACATTGACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAGCAGTCTGAGATCTGAGGACA CCGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGACCCTGGTCACTGTCTCTAGCGCCAAAACGAAGGGCCCATC CGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTG GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACT CTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACC TACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTT GAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGG GACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCG GACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGT CCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCC GCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCT GCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT CAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC TCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGC AGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTA CACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTCAGACCCCCACCAAC ACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCAACAACAGCAACCCC AAGCCCAACCCCGCTAGTAACCTGTGGGTGACCGTGTACTACGGCGTGCCCGTGT GGAAGGGCGCCACCACCACCCTGTTCTGCGCCAGCGACGCCAAGGCCTACGACA CCGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGCCCGCCGACCCCAACC CCCAGGAGATGGTGCTGGAGAACGTGACCGAGAACTTCAACATGTGGAAGAACG AGATGGTGAACCAGATGCAGGAGGACGTCATCAGCCTGTGGGACCAGAGCCTGA AGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGGAGTGCAGGAACGTGA GCAGCAACAGCAACGACACCTACCACGAGACCTACCACGAGAGCATGAAGGAG ATGAAGAACTGCAGCTTCAACGCCACCACCGTGGTGAGGGACAGGAAGCAGACC GTGTACGCCCTGTTCTACAGGCTGGACATCGTGCCCCTGACCAAGAAGAACTACA GCGAGAACAGCAGCGAGTACTACAGGCTGATCAACTGCAACACCAGCGCCATCA CCCAGGCCTGCCCCAAGGTGACCTTCGACCCCATCCCCATCCACTACTGCACCCC CGCCGGCTACGCCATCCTGAAGTGCAACGACAAGATCTTCAACGGCACCGGCCC CTGCCACAACGTGAGCACCGTGCAGTGCACCCACGGCATCAAGCCCGTGGTGAG CACCCAGCTGCTGCTGAACGGCAGCCTGGCCGAGGGCGAGATCATCATCAGGAG CGAGAACCTGACCAACAACGTGAAAACCATCATCGTGCACCTGAACCAGAGCGT GGAGATCGTGTGCACCAGGCCCGGCAACAACACCAGGAAGAGCATCAGGATCGG CCCCGGCCAGACCTTCTACGCCACCGGCGACATCATCGGCGACATCAGGCAGGC CCACTGCAACATCAGCGAGGACAAGTGGAACGAGACCCTGCAGAGGGTGAGCA AGAAGCTTGCCGAGCACTTCCAGAACAAGACCATCAAGTTCGCC AGCAGCAGCG GCGGCGACCTGGAGGTGACCACCCACAGCTTCAACTGCAGGGGCGAGTTCTTCT ACTGCAACACCAGCGGCCTGTTCAACGGCGCCTACACCCCCAACGGCACCAAGA GCAACAGCAGCAGCATCATCACCATCCCCTGCAGGATCAAGCAGATCATCAACA TGTGGCAGGAGGTGGGCAGGGCCATGTACGCCCCTCCCATCAAGGGCAACATCA CCTGCAAGAGCAACATCACCGGCCTGCTGCTGGTGAGGGACGGCGGCACCGAGC CCAACGACACCGAGACCTTCAGGCCCGGCGGCGGCGACATGAGGAACAACTGGA GGAGCGAGCTGTACAAGTACAAGGTGGTGGAGATCAAGCCCCTGGGCGTGGCCC CCACCACCACCAAGAGGAGGGTGGTGGAGAGGGAGAAGAGCGCCGTGGGCATC GGCGCCGTGTTCCTGGGCTTCCTGGGCGTGGCCGGCAGCACCATGGGCGCCGCCA GCATCACCCTGACCGTGCAGGCCAGGCAGCTGCTGAGCGGCATCGTGCAGCAGC AGAGCAACCTGCTGAGGGCCATCGAGGCCCAGCAGCACCTGCTGCAGCTGACCG TGTGGGGCATCAAGCAGCTGCAGACCAGGGTGCTGGCCATCGAGAGGTACCTGA AGGACCAGCAGCTGCTGGGCATCTGGGGCTGCAGCGGCAAGCTGATCTGCACCA CCGCCGTGCCCTGGAACAGCAGCTGGAGCAACAAGAGCCAGAAGGAGATCTGGG ACAACATGACCTGGATGCAGTGGGACAAGGAGATCAGCAACTACACCAACACCG TGTACAGGCTGCTGGAGGAGAGCCAGAACCAGCAGGAGAGGAACGAGAAGGAC CTGCTGGCCCTGGACAGCCATCACCATCACCATCACTGA(SEQ ID NO :34)

H chain secreted product IgG4H(imderline), flexible lin er(bold italics), gpl40 (bold underline) from HIV-1 CN54 (Clade C)

EIOLVQSGSELK PGASVKISCKASGYPFTDYIMVWVKOAHGKGLEWIGNISPYYGT TNYNLKFKGPvATLTVDKSTSTAYMELSSLRSEDTAVYYCARSPNWDGAWFAHWGQ GTLVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW SGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPP CPAPEFEGGPSVFLFPPKP DTLMISRTPEVTCVVVDVSOEDPEVOFNWYVDGVEVH NAKTKPREEQFNSTYRVVSVLTVLHODWLNGKEYKCKVSNKGLPSSIEKTISKAKGQ PREPOVYTLPPSOEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALHNHYTQ SLSLSLG ASOJP77VT/ SVTPTNNSTPTNNSNPKPNPASNLy/YT\YYG\FYWKGATTTLFCAST>AKAY E VHNVWATHACVPADPNPOEMVLENVTENFNMWKNEMVNOMQEDVISLWDOS LKPCVKLTPLCVTLECRNVSSNSNDTYHETYHESMKEMKNCSFNATTVVRDRK OTVYALFYRLDIVPLTKKNYSENSSEYYRLINCNTSAITQACPKVTFDPIPIHYCT PAGYAILKCNDKIFNGTGPCHNVSTVQCTHGIKPVVSTQLLLNGSLAEGEHIRSE NLTNNVKTIIVHLNOSVEIVCTRPGNNTRKSIRIGPGOTFYATGDHGDIRQAHCN ISED WNETLORVSKKLAEHFQNKTIKFASSSGGDLEVTTHSFNCRGEFFYCNTS GLFNGAYTPNGTKSNSSSIITIPCRIKQIINMWQEVGRAMYAPPIKGNITCKSNIT GLLLVRDGGTEPNDTETFRPGGGDMRNNWRSELYKYKVVEIKPLGVAPTTTKR RVVEREKSAVGIGAVFLGFLGVAGSTMGAASITLTVOAROLLSGIVOOOSNLLR AIEAOOHLLOLTVWGIKOLOTRVLAIERYLKDOQLLGIWGCSGKLICTTAVPW NSSWSNKSO EIWDNMTWMQWDKEISNYTNTVYRLLEESONOQERNEKDLLA LDSHHHHHHfSEQ ID NO :35)

C2289 [hAnti-LOX-lVH3-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-Z-6xHis]

ATGGGTTGGAGCCTCATCTTGCTCTTCCTTGTCGCTGTTGCTACGCGTGTCCACTC CGAGATCCAGCTGGTGCAGAGCGGAAGCGAGCTGAAGAAGCCTGGGGCTTCAGT GAAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGG GTGAGGCAGGCCCCTGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTAC TATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACATTGACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAGCAGTCTGAGATCTGAGGACA CCGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTAGCGCCAAAACGAAGGGCCCATC CGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTG GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACT CTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACC TACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTT GAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGG GACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCG GACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGT CCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCC GCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCT GCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT CAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC TCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGC AGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTA CACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTCAGACCCCCACCAAC ACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCAACAACAGCAACCCC AAGCCCAACCCCGCTAGTAACCTGTGGGTGACCGTGTACTACGGCGTGCCCGTGT GGAAGGAGGCCAAGACCACCCTGTTCTGCGCCAGCGACGCCAAGAGCTACGAGA AGGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGCCCACCGACCCCAACC CCCAGGAGATCGTGCTGGGCAACGTGACCGAGAACTTCAACATGTGGAAGAACG ACATGGTGGACCAGATGCACGAGGACATCATCAGCCTGTGGGACCAGAGCCTGA AGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGAACTGCACCGAGGTGA ACGTGACCCGCAACGTGAACAACAGCGTGGTGAACAACACCACCAACGTGAACA ACAGCATGAACGGCGACATGAAGAACTGCAGCTTCAACATCACCACCGAGCTGA AGGACAAGAAGAAGAACGTGTACGCCCTGTTCTACAAGCTGGACATCGTGAGCC TGAACGAGACCGACGACAGCGAGACCGGCAACAGCAGCAAGTACTACCGCCTGA TCAACTGCAACACCAGCGCCCTGACCCAGGCCTGCCCCAAGGTGAGCTTCGACCC CATCCCCATCCACTACTGCGCCCCCGCCGGCTACGCCATCCTGAAGTGCAACAAC AAGACCTTCAACGGCACCGGCCCCTGCCACAACGTGAGCACCGTGCAGTGCACC CACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCTGAACGGCAGCCTGGCC GAGGAGGGCATCATCATCCGCAGCGAGAACCTGACCAACAACGTCAAGACCATC ATCGTGCACCTGAACCGCAGCATCGAGATCGTGTGCGTGCGCCCCAACAACAAC ACCCGCCAGAGCATCCGCATCGGCCCCGGCCAGACCTTCTACGCCACCGGCGAC ATCATCGGCGACATCCGCCAGGCCCACTGCAACATCAGCCGCACCAACTGGACC AAGACCCTGCGCGAGGTGCGCAACAAGCTGCGCGAGCACTTCCCCAACAAGAAC ATCACCTTCAAGCCCAGCAGCGGCGGCGACCTGGAGATCACCACCCACAGCTTC AACTGCCGCGGCGAGTTCTTCTACTGCAACACCAGCGGCCTGTTCAGCATCAACT ACACCGAGAACAACACCGACGGCACCCCCATCACCCTGCCCTGCCGCATCCGCC AGATCATCAACATGTGGCAGGAGGTGGGCCGCGCCATGTACGCCCCCCCCATCG AGGGCAACATCGCCTGCAAGAGCGACATCACCGGCCTGCTGCTGGTGCGCGACG GCGGCAGCACCAACGACAGCACCAACAACAACACCGAGATCTTCCGCCCCGCCG GCGGCGACATGCGCGACAACTGGCGCAGCGAGCTGTACAAGTACAAGGTGGTGG AGATCAAGCCCCTGGGCATCGCCCCCACCGAGGCCAAGCGCCGCGTGGTGGAGC GCGAGAAGCGCGCCGTGGGCATCGGCGCCGTGTTCCTGGGCTTCCTGGGCGCCG CCGGCAGCACCATGGGCGCCGCCAGCATCACCCTGACCGCCCAGGCCCGCCAGG TGCTGAGCGGCATCGTGCAGCAGCAGAGCAACCTGCTGCGCGCCATCGAGGCCC AGCAGCACCTGCTGCAGCTGACCGTGTGGGGCATCAAGCAGCTGCAGACCCGCG TGCTGGCCATCGAGCGCTACCTGAAGGACCAGCAGCTGCTGGGCCTGTGGGGCT GCAGCGGCAAGCTGATCTGCACCACCGCCGTGCCCTGGAACATCAGCTGGAGCA ACAAGAGCAAGACCGACATCTGGGACAACATGACCTGGATGCAGTGGGACCGCG AGATCAGCAACTACACCAACACCATCTACCGCCTGCTGGAGGACAGCCAGAGCC AGCAGGAGCAGAACGAGAAGGACCTGCTGGCCCTGGACAGCTGGAACAACCTGT GGAACTGGTTCGACATCACCAAGTGGCTGTGGTACATCAAGGCTAGCCACCATC ACCATCACCATTGA(SEQ ID NO :36)

H chain secreted product IgG4H(underline), flexible linker(Ao/rf italics), gpl40 (bold underline) from HIV-196ZM651 (Clade C)

EIOLVOSGSELKKPGASVKISCKASGYPFTDYIMVWVROAPGKGLEWIGNISPYYGTT NYNLKFKGRATLTVDKSTSTAYMELSSLRSEDTAVYYCARSPNWDGAWFAHWGQG ALVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLOSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPP CPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSOEDPEVQFNWYVDGVEVH NAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIE TISKAKGQ PREPOVYTLPPSOEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS07y7 V7Y SVTPTNNSTPTNNSNPKPNPASNL\VVTVYYGV¥V\VKEAKTTLFCASI)AKSYEKE VHNVWATHACVPTDPNPOEIVLGNVTENFNMWKNDMVDOMHEDIISLWDQSL KPCVKLTPLCVTLNCTEVNVTRNVNNSVVNNTTNVNNSMNGDMKNCSFNITTE LKDKKKNVYALFYKLDIVSLNETDDSETGNSSKYYRLINCNTSALTQACPKVSFD PIPIHYCAPAGYAILKCNNKTFNGTGPCHNVSTVOCTHGIKPVVSTQLLLNGSLA EEGIHRSENLTNNVKTIIVHLNRSIEIVCVRPNNNTRQSIRIGPGOTFYATGDHGD IROAHCNISRTNWTKTLREVRNKLREHFPNKNITFKPSSGGDLEITTHSFNCRGE FFYCNTSGLFSINYTENNTDGTPITLPCRIROIINMWQEVGRAMYAPPIEGNIACK SDITGLLLVRDGGSTNDSTNNNTEIFRPAGGDMRDNWRSELYKYKVVEIKPLGI APTEAKRRVVEREKRAVGIGAVFLGFLGAAGSTMGAASITLTAQAROVLSGIVO OOSNLLRAIEAOOHLLOLTVWGIKOLQTRVLAIERYLKDOOLLGLWGCSGKLI CTTAVPWNISWSNKSKTDIWDNMTWMOWDREISNYTNTIYRLLEDSOSOOEON EKDLLALDS NNLWNWFDITKWLWYI ASHHHHHH(SEQ ID NO :37)

C2290 [hAnti-LOX-lVH3-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-S-6xHis]

ATGGGTTGGAGCCTCATCTTGCTCTTCCTTGTCGCTGTTGCTACGCGTGTCCACTC CGAGATCCAGCTGGTGCAGAGCGGAAGCGAGCTGAAGAAGCCTGGGGCTTCAGT GAAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGG GTGAGGCAGGCCCCTGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTAC TATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACATTGACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAGCAGTCTGAGATCTGAGGACA CCGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTAGCGCCAAAACGAAGGGCCCATC CGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTG GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACT CTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACC TACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTT GAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGG GACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCG GACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGT CCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCC GCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCT GCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT CAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC TCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGC AGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTA CACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTCAGACCCCCACCAAC ACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCAACAACAGCAACCCC AAGCCCAACCCCGCTAGTGTAGAAAAATTGTGGGTCACAGTCTATTATGGGGTAC CTGTGTGGAAAGAAGCAACCACCACTCTATTTTGTGCATCAGATGCTAAAGCCTA TGACACAGAGGTACATAATGTCTGGGCCACACATGCCTGTGTACCCACAGACCCT AACCCACAAGAAATAGTATTGGAAAATGTGACAGAAAATTTTAACATGTGGAAA AATAACATGGTAGAACAGATGCATGAGGATATAATCAGTTTATGGGATCAAAGT CTAAAGCCATGTGTAAAGTTAACCCCACTCTGTGTTACTCTACATTGCACTAATTT GAAGAATGCTACTAATACCAAGAGTAGTAATTGGAAAGAGATGGACAGAGGAG AAATAAAAAATTGCTCTTTCAAGGTCACCACAAGCATAAGAAATAAGATGCAGA AAGAATATGCACTTTTTTATAAACTTGATGTAGTACCAATAGATAATGATAATAC AAGCTATAAATTGATAAATTGTAACACCTCAGTCATTACACAGGCCTGTCCAAAG GTATCCTTTGAACCAATTCCCATACATTATTGTGCCCCGGCTGGTTTTGCGATTCT AAAGTGTAATGATAAGAAGTTCAATGGATCAGGACCATGTACAAATGTCAGCAC AGTACAATGTACACATGGAATTAGGCCAGTAGTGTCAACTCAATTGCTGTTAAAT GGCAGTCTAGCAGAAGAAGGGGTAGTAATTAGATCTGAAAATTTCACAGACAAT GCTAAAACTATAATAGTACAGCTGAAGGAATCTGTAGAAATTAATTGTACAAGA CCTAACAATAATACAAGAAAAAGTATAACTATAGGACCGGGGAGAGCATTTTAT GCAACAGGAGACATAATAGGAGATATAAGACAAGCACATTGTAACATTAGTGGA GAAAAATGGAATAACACTTTAAAACAGATAGTTACAAAATTACAAGCACAATTT GGGAATAAAACAATAGTCTTTAAGCAATCCTCAGGAGGGGACCCAGAAATTGTA ATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATTCAACACAGCTTTT TAATAGTACTTGGAATAATACTATAGGGCCAAATAACACTAATGGAACTATCAC ACTCCCATGCAGAATAAAACAAATTATAAACAGGTGGCAGGAAGTAGGAAAAGC AATGTATGCCCCTCCCATCAGAGGACAAATTAGATGCTCATCAAATATTACAGGA CTGCTATTAACAAGAGATGGTGGTAAAGAGATCAGTAACACCACCGAGATCTTC AGACCTGGAGGTGGAGATATGAGGGACAATTGGAGAAGTGAATTATATAAATAT AAAGTAGTAAAAATTGAGCCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAG AGTGGTGCAGAGAGAAAAAAGAGCAGTGACGCTAGGAGCTATGTTCCTTGGGTT CTTGGGAGCAGCAGGAAGCACTATGGGCGCAGCGTCACTGACGCTGACGGTACA GGCCAGACAATTATTGTCTGGTATAGTGCAACAGCAGAACAATTTGCTGAGAGCT ATTGAGGCGCAACAGCATCTGTTGCAACTCACAGTCTGGGGCATCAAGCAGCTCC AGGCAAGAGTCCTGGCTGTGGAAAGATACCTAAAGGATCAACAGCTCCTAGGGA TTTGGGGTTGCTCTGGAAAACTCATTTGCACCACTGCTGTGCCTTGGAATGCTAG TTGGAGTAATAAATCTCTGGATCAGATTTGGAATAACATGACCTGGATGGAGTGG GAGAGAGAAATTGACAATTACACAAACTTAATATACACCTTAATTGAAGAATCG CAGAACCAACAAGAAAAGAATGAACAAGAATTATTAGAATTGGATAAGTGGGC AAGTTTGTGGAATTGGTTTGACATATCAAAATGGCTGTGGTATATAAAAGCTAGC CACCATCACCATCACCATTGA(SEQ ID NO :38)

H chain secreted product IgG4H(underline), flexible \inker(bold italics), pl40 (bold underline) from SF162, a clade B strain

EIOLVOSGSELKKPGASVKISCKASGYPFTDYIMVWVROAPGKGLEWIGNISPYYGTT NYNLKFKGRATLTVDKSTSTAY ELSSLRSEDTAVYYCARSPNWDGAWFAHWGQG ALVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLV DYFPEPVTVSWNSGALTSGV HTFPAVLQS S GL YSLS S V VTVPS S SLGTKTYTCN VDHKPSNTKVDKRVESKYGPPCPP CPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVH NAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIE TISKAKGQ PREPOVYTLPPSQEEMTKNOVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPVLD SDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKASOr rNr/ SVTPTNNSTPTNNSNPKPNPASVEKLWYTVYYGYPYWKEATTTLFCASOAKAYD TEVHNVWATHACVPTDPNPOEIVLENVTENFNMWKNNMVEOMHEDHSLWDO SLKPCVKLTPLCVTLHCTNL NATNTKSSNWKEMDRGEIKNCSFKVTTSIRNK MOKEYALFYKLDVVPIDNDNTSYKLINCNTSVITOACPKVSFEPIPIHYCAPAGFA ILKCND KFNGSGPCTNVSTVOCTHGIRPVVSTOLLLNGSLAEEGVVIRSENFTD NAKTIIVOLKESVEINCTRPNNNTRKSITIGPGRAFYATGDIIGDIROAHCNISGEK WNNTLKOIVT LOAQFGNKTIVFKOSSGGDPEIVMHSFNCGGEFFYCNSTOLFN STWNNTIGPNNTNGTITLPCRIKOIINRWQEVGKAMYAPPIRGOIRCSSNITGLLL TRDGGKEISNTTEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVV OREKRAVTLGAMFLGFLGAAGSTMGAASLTLTVQAROLLSGIVOOONNLLRAI EAOOHLLOLTVWGIKOLOARVLAVERYLKDOOLLGIWGCSGKLICTTAVP N ASWSN SLDOIWNNMTWMEWEREIDNYTNLIYTLIEESQNOQEKNEOELLELD KWASLWNWFDISKWLWYIKASHHHHHHfSEQ ID NO :39) C2291 [hAnti-LOX-lVH3-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-B-6xHis]

ATGGGTTGGAGCCTCATCTTGCTCTTCCTTGTCGCTGTTGCTACGCGTGTCCACTC CGAGATCCAGCTGGTGCAGAGCGGAAGCGAGCTGAAGAAGCCTGGGGCTTCAGT GAAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGG GTGAGGCAGGCCCCTGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTAC TATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACATTGACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAGCAGTCTGAGATCTGAGGACA CCGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTAGCGCCAAAACGAAGGGCCCATC CGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTG GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACT CTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACC TACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTT GAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGG GACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCG GACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGT CCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCC GCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCT GCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT CAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC TCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGC AGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTA CACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTCAGACCCCCACCAAC ACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCAACAACAGCAACCCC AAGCCCAACCCCGCTAGTGTATGGAAGGATGCCACTACTACACTTTTCTGTGCGT CCGACGCCAAAGCCTATGATAAAGAGGTCCACAATGTATGGGCCACACACGCAT GTGTGCCCACCGATCCTAATCCTCAAGAAGTTGTCCTGGGGAACGTTACTGAGAA TTTCAACATGGGTAAGAATAACATGGTAGAACAGATGCACGAAGATATTATTTCC CTGTGGGATCAGTCCCTGAAGCCATGCGTGAAGTTGACACCCCTGTGTGTCACCC TGAATTGCACCGAGCTGAAAAACAGTACCGACACCAATCTGGGTACACAGGAGA TGAAGAACTGTTCCTTTAACATTACGACCTCAGTGCGGAATAAGATGAAACGCG AGTATGCACTCTTTTACAGCCTCGACATTGTTCCCATTGACAATGACAACACTAG CTATAGGCTGCGGTCATGTAATACATCAATCGTCACGCAAGCCTGCCCTAAGGTC TCTTTCGAACCAATTCCGATTCACTTTTGTGCACCGGCTGGATTTGCCATTCTGAA GTGTAATAACAAAACTTTTAACGGGACCGGACCCTGCACGAACGTGTCTACAGT GCAGTGCACTCACGGGATTAGACCTGTCGTGTCCACGCAGCTGTTGCTGAACGGG TCACTGGCTGAGGAGGAAGTGGTGATTCGGAGTGAAAATTTCACCAACAATGCC AAGACCATAATCGTGCAACTTAATGAGTCTGTGGAGATAAACTGTACTAGGCCTA ACAATAACACTCGGAAGTCTATACATATTGGGCCCGGCAGAGCTTTCTACACCAC TGGCGACATCATCGGCGATATCAGACAAGCTCATTGCAACATCAGTCGCACCAAT TGGACCAACACCTTGAAGCGCGTGGCGGAAAAGCTTCGAGAGAAATTCAACAAT ACCACAATCGTCTTCAATCAGTCTAGCGGAGGTGATCCCGAGATAGTTATGCATT CATTTAACTGCGGAGGCGAGTTCTTTTACTGCAATACTACACAGCTTTTCAACTCC ACCTGGAACGAGACTAACAGCGAAGGCAATATAACATCCGGCACCATCACACTC CCATGCCGCATCAAGCAGATCATCAACATGTGGCAGGAGGTGGGCAAAGCTATG TACGCACCACCAATAGGCGGCCAGATCAAATGCTTGAGTAACATCACAGGCCTC CTCCTGACGAGGGACGGAGGTAGCGATAATAGCAGCAGTGGAAAAGAAATCTTT CGACCAGGGGGGGGTGACATGAGAGACAATTGGAGGAGCGAACTGTACAAGTA TAAAGTGGTTATCATTGAGCCTCTCGGAATCGCCCCCACAGCTAGTAAAGCCAAA CGGAGAGTAGTTCAGAGGGAAAAAAGAGCCGTCGGTATCGGGGCAATGTTCTTG GGCTTTCTGGGAGCCGCTGGGAGCACGATGGGGGCGGCCAGCCTTACTCTGACA GTGCAGGCCCGCCAGCTGCTTAGTGGCATTGTGCAGCAACAGAACAATCTTCTCA GGGCAATCGAGGCCCAGCAGCACCTCCTGCAGTTGACAGTGTGGGGAATCAAGC AGCTCCAGGCACGAGTCCTGGCTCTGGAGCGCTACTTGCAGGATCAACGGTTCCT TGGAATGTGGGGCTGTAGCGGCAAGCTCATTTGCACAACTGCGGTGCCCTGGAAT GCTAGTTGGTCTAACAAGAACCTGTCCCAAATATGGGATAACATGACCTGGATG GAGTGGGAACGAGAAATTTCAAATTATACCGAGATTATATATTCTTTGATCGAGG AATCACAAAATCAGCAGGAAAAGAACGAGTTGGACCTCCTCCAACTGGACAAAT GGGCTTCCCTGTGGAATTGGTTTAACATCACCAATTGGCTGTGGTACATCAAGGC TAGCCATCACCATCACCATCACTGA(SEQ ID NO :40)

H chain secreted product IgG4H(underline), flexible \inker(bold italics), gpl40 (bold underline) from HIV-1 BX08 clade B

EIOLVQSGSELKKPGASVKISCKASGYPFTDYI VWVRQAPGKGLEWIGNISPYYGTT NYNLKFKGRATLTVD STSTAYMELSSLRSEDTAVYYCARSPNWDGAWFAHWGOG ALVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLOSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVD RVESKYGPPCPP CPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVOFNWYVDGVEVH NAKTKPREEOFNSTYRVVSVLTVLFIQDWLNGKEYKCKVSNKGLPSSIEKTIS AKGO PREPOVYTLPPSOEEMTKNQVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPVLD SDGSFFLYSRLTVDKSRWOEGNVFSCSVMHEALH HYTOKSLSLSLGKASOJ 77V7¹/ SVTPTNNSTPTNNSNPKPNPASVV/KOATTTT FCASOAKAYOKEVimVWATHACV PTDPNPOEVVLGNVTENFNMGKNNMVEOMHEDIISLWDQSLKPCVKLTPLCVT LNCTELKNSTDTNLGTQEMKNCSFNITTSVRNKMKREYALFYSLDIVPIDNDNTS YRLRSCNTSIVTOACPKVSFEPIPIHFCAPAGFAILKCNNKTFNGTGPCTNVSTVQ CTHGIRPVVSTOLLLNGSLAEEEVVIRSENFTNNAKTIIVQLNESVEINCTRPNNN TRKSIHIGPGRAFYTTGDIIGDIROAHCNISRTNWTNTLKRVAEKLREKFNNTTI VFNOSSGGDPEIVMHSFNCGGEFFYCNTTQLFNSTWNETNSEGNITSGTITLPCRI KOIINMWOEVGKAMYAPPIGGOIKCLSNITGLLLTRDGGSDNSSSGKEIFRPGG GDMRDNWRSELYKYKVVIIEPLGIAPTASKAKRRVVOREKRAVGIGAMFLGFL GAAGSTMGAASLTLTVQAROLLSGIVOOONNLLRAIEAOOHLLOLTVWGIKOL OARVLALERYLODORFLGMWGCSGKLICTTAVPWNASWSNKNLSQIWDNMT WMEWEREISNYTEIIYSLIEESONOOEKNELDLLOLDKWASLWNWFNITNWLW YIKASHHHHHH(SEQ ID NO :41)

C2292 [hAnti-DCIRVHl-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-Z-6xHis]

ATGGGTTGGAGCCTCATCTTGCTCTTCCTTGTCGCTGTTGCTACGCGTGTCCACTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGCCATAGTGAAGCCCACCCAGACCCTC ACCCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGCCCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAAGAACCAGGTTGTGCTCACCATGACCATTGTGGACACTGTGGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCCAGGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTAACCTGTGGGTGACCGTGTACT ACGGCGTGCCCGTGTGGAAGGAGGCCAAGACCACCCTGTTCTGCGCCAGCGACG CCAAGAGCTACGAGAAGGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGC CCACCGACCCCAACCCCCAGGAGATCGTGCTGGGCAACGTGACCGAGAACTTCA ACATGTGGAAGAACGACATGGTGGACCAGATGCACGAGGACATCATCAGCCTGT GGGACCAGAGCCTGAAGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGA ACTGCACCGAGGTGAACGTGACCCGCAACGTGAACAACAGCGTGGTGAACAACA CCACCAACGTGAACAACAGCATGAACGGCGACATGAAGAACTGCAGCTTCAACA TCACCACCGAGCTGAAGGACAAGAAGAAGAACGTGTACGCCCTGTTCTACAAGC TGGACATCGTGAGCCTGAACGAGACCGACGACAGCGAGACCGGCAACAGCAGC AAGTACTACCGCCTGATCAACTGCAACACCAGCGCCCTGACCCAGGCCTGCCCCA AGGTGAGCTTCGACCCCATCCCCATCCACTACTGCGCCCCCGCCGGCTACGCCAT CCTGAAGTGCAACAACAAGACCTTCAACGGCACCGGCCCCTGCCACAACGTGAG CACCGTGCAGTGCACCCACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCT GAACGGCAGCCTGGCCGAGGAGGGCATCATCATCCGCAGCGAGAACCTGACCAA CAACGTCAAGACCATCATCGTGCACCTGAACCGCAGCATCGAGATCGTGTGCGT GCGCCCCAACAACAACACCCGCCAGAGCATCCGCATCGGCCCCGGCCAGACCTT CTACGCCACCGGCGACATCATCGGCGACATCCGCCAGGCCCACTGCAACATCAG CCGCACCAACTGGACCAAGACCCTGCGCGAGGTGCGCAACAAGCTGCGCGAGCA CTTCCCCAACAAGAACATCACCTTCAAGCCCAGCAGCGGCGGCGACCTGGAGAT CACCACCCACAGCTTCAACTGCCGCGGCGAGTTCTTCTACTGCAACACCAGCGGC CTGTTCAGCATCAACTACACCGAGAACAACACCGACGGCACCCCCATCACCCTGC CCTGCCGCATCCGCCAGATCATCAACATGTGGCAGGAGGTGGGCCGCGCCATGT ACGCCCCCCCCATCGAGGGCAACATCGCCTGCAAGAGCGACATCACCGGCCTGC TGCTGGTGCGCGACGGCGGCAGCACCAACGACAGCACCAACAACAACACCGAGA TCTTCCGCCCCGCCGGCGGCGACATGCGCGACAACTGGCGCAGCGAGCTGTACA AGTACAAGGTGGTGGAGATCAAGCCCCTGGGCATCGCCCCCACCGAGGCCAAGC GCCGCGTGGTGGAGCGCGAGAAGCGCGCCGTGGGCATCGGCGCCGTGTTCCTGG GCTTCCTGGGCGCCGCCGGCAGCACCATGGGCGCCGCCAGCATCACCCTGACCG CCCAGGCCCGCCAGGTGCTGAGCGGCATCGTGCAGCAGCAGAGCAACCTGCTGC GCGCCATCGAGGCCCAGCAGCACCTGCTGCAGCTGACCGTGTGGGGCATCAAGC AGCTGCAGACCCGCGTGCTGGCCATCGAGCGCTACCTGAAGGACCAGCAGCTGC TGGGCCTGTGGGGCTGCAGCGGCAAGCTGATCTGCACCACCGCCGTGCCCTGGA ACATCAGCTGGAGCAACAAGAGCAAGACCGACATCTGGGACAACATGACCTGGA TGCAGTGGGACCGCGAGATCAGCAACTACACCAACACCATCTACCGCCTGCTGG AGGACAGCCAGAGCCAGCAGGAGCAGAACGAGAAGGACCTGCTGGCCCTGGAC AGCTGGAACAACCTGTGGAACTGGTTCGACATCACCAAGTGGCTGTGGTACATC AAGGCTAGCCACCATCACCATCACCATTGA(SEQ ID NO :42)

H chain secreted product IgG4H(underline), flexible linker(Z>o/rf italics), gpl40 (bold underline) from HIV-196ZM651 (Clade C)

OVTLKESGPAIVKPTQTLTLTCSFSGFSLSTSG GLSWIRQPSG ALEWLAHIYWDDD RYNPSLKSRLTISKDTSKNQVVLTMTIVDTVDAATYYCARSSHYYGYGYGGYFDV WGOGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT TYTCNVDHKPSNTKVDKRVESKYG PPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDG VEVH A TKPREEOFNSTYRVVSVLTVLHODWLNGKEYKCKVSNKGLPSSIEKTISK AKGQPREPQVYTLPPSOEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN Y TTP PVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTOKSLSLSLGKASgrP TNTISVTPTNNSTPTNNSNPKPNPASNLWYTYYYGYVYWKEAKTTLFCASOAKSY EKEVHNVWATHACVPTDPNPOEIVLGNVTENFNMWKNDMVDQMHEDIISLWD OSLKPCVKLTPLCVTLNCTEVNVTRNVNNSVVNNTTNVNNSMNGDMKNCSFNI TTELKDKKKNVYALFYKLDIVSLNETDDSETGNSSKYYRLINCNTSALTQACPK VSFDPIPIHYCAPAGYAILKCNN TFNGTGPCHNVSTVOCTHGI PVVSTQLLLN GSLAEEGIIIRSENLTNNVKTIIVHLNRSIEIVCVRPNNNTRQSIRIGPGOTFYATG DIIGDIROAHCNISRTNWTKTLREVRNKLREHFPNKNITFKPSSGGDLEITTHSFN CRGEFFYCNTSGLFSINYTENNTDGTPITLPCRIROIINMWQEVGRAMYAPPIEG NIACKSDITGLLLVRDGGSTNDSTNNNTEIFRPAGGDMRDNWRSELYKYKVVEI KPLGIAPTEAKRRVVEREKRAVGIGAVFLGFLGAAGSTMGAASITLTAQARQVL SGIVOOOSNLLRAIEAQOHLLOLTVWGIKOLOTRVLAIERYLKDOOLLGLWGC SGKLICTTAVPWNISWSNKSKTDIWDNMTWMOWDREISNYTNTIYRLLEDSQS OOEONEKDLLALDSWNNLWNWFDITKWLWYIKASHHHHHH(SEO ID NO :43)

CI 854 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl20-B]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTGTATGGAAGGATGCCACTACTA CACTTTTCTGTGCGTCCGACGCCAAAGCCTATGATAAAGAGGTCCACAATGTATG GGCCACACACGCATGTGTGCCCACCGATCCTAATCCTCAAGAAGTTGTCCTGGGG AACGTTACTGAGAATTTCAACATGGGTAAGAATAACATGGTAGAACAGATGCAC GAAGATATTATTTCCCTGTGGGATCAGTCCCTGAAGCCATGCGTGAAGTTGACAC CCCTGTGTGTCACCCTGAATTGCACCGAGCTGAAAAACAGTACCGACACCAATCT GGGTACACAGGAGATGAAGAACTGTTCCTTTAACATTACGACCTCAGTGCGGAA TAAGATGAAACGCGAGTATGCACTCTTTTACAGCCTCGACATTGTTCCCATTGAC AATGACAACACTAGCTATAGGCTGCGGTCATGTAATACATCAATCGTCACGCAA GCCTGCCCTAAGGTCTCTTTCGAACCAATTCCGATTCACTTTTGTGCACCGGCTGG ATTTGCCATTCTGAAGTGTAATAACAAAACTTTTAACGGGACCGGACCCTGCACG AACGTGTCTACAGTGCAGTGCACTCACGGGATTAGACCTGTCGTGTCCACGCAGC TGTTGCTGAACGGGTCACTGGCTGAGGAGGAAGTGGTGATTCGGAGTGAAAATT TCACCAACAATGCCAAGACCATAATCGTGCAACTTAATGAGTCTGTGGAGATAA ACTGTACTAGGCCTAACAATAACACTCGGAAGTCTATACATATTGGGCCCGGCAG AGCTTTCTACACCACTGGCGACATCATCGGCGATATCAGACAAGCTCATTGCAAC ATCAGTCGCACCAATTGGACCAACACCTTGAAGCGCGTGGCGGAAAAGCTTCGA GAGAAATTCAACAATACCACAATCGTCTTCAATCAGTCTAGCGGAGGTGATCCCG AGATAGTTATGCATTCATTTAACTGCGGAGGCGAGTTCTTTTACTGCAATACTAC ACAGCTTTTCAACTCCACCTGGAACGAGACTAACAGCGAAGGCAATATAACATC CGGCACCATCACACTCCCATGCCGCATCAAGCAGATCATCAACATGTGGCAGGA GGTGGGCAAAGCTATGTACGCACCACCAATAGGCGGCCAGATCAAATGCTTGAG TAACATCACAGGCCTCCTCCTGACGAGGGACGGAGGTAGCGATAATAGCAGCAG TGGAAAAGAAATCTTTCGACCAGGGGGGGGTGACATGAGAGACAATTGGAGGA GCGAACTGTACAAGTATAAAGTGGTTATCATTGAGCCTCTCGGAATCGCCCCCAC AGCTAGCTGA(SEQ ID NO :44)

H chain secreted product IgG4H(underline), flexible linker(6o/rf italics), gpl20 (bold underline) from HIV-1 BX08 clade B

OVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGLEWLAHIYWDDD KRYNPSL SRLTISKDTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP CPPCPAPEFEGGPSVFLFPPKPKDTL ISRTPEVTCVVVDVSQEDPEVOFNWYVDGVE VHNAKTKPREEOFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIE TISKAK GQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTOKSLSLSLGKASOJPy NTIS VTPTNNSTPTNNSNPKPNPAS\WKOATTTL¥CASOAKAYOKEVHN\V^AJ}i ACVPTDPNPOEVVLGNVTENFNMGKNNMVEQMHEDIISLWDOSLKPCVKLTPL CVTLNCTELKNSTDTNLGTOEMKNCSFNITTSVRNKMKREYALFYSLDIVPIDN DNTSYRLRSCNTSIVTQACPKVSFEPIPIHFCAPAGFAILKCNNKTFNGTGPCTNV STVOCTHGIRPVVSTOLLLNGSLAEEEVVIRSENFTNNAKTIIVQLNESVEINCTR PNNNTRKSIHIGPGRAFYTTGDIIGDIROAHCNISRTNWTNTLKRVAEKLREKFN NTTIVFNQSSGGDPEIVMHSFNCGGEFFYCNTTQLFNSTWNETNSEGNITSGTITL PCRIKOIINMWOEVGKAMYAPPIGGQIKCLSNITGLLLTRDGGSDNSSSGKEIFR PGGGDMRDNWRSELYKYKVVIIEPLGIAPTAS (SEQ ID NO :45)

C1899 [mAnti-LOX-115C4H-LV-hIgG4H-C-FIex-vl-ViralenvHIV-gp41-B-6xHis]

ATGGGAGGGATCTGGATCTTTCTCTTCCTCCTGTCAGGAACTGCAGGTGCCCACT CTGAGATCCAGCTGCAGCAGACTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAG TGAAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTG GGTGAAGCAGAGCCATGGAAAGAGCCTTGAGTGGATTGGAAATATTAGTCCTTA CTATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAAGGCCACATTGACTGTA GACAAATCTTCCAGCACAGCCTACATGCAGCTCAACAGTCTGACATCTGAGGACT CTGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTGCAGCCAAAACAAAGGGCCCATC CGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTG GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACT CTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACC TACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTT GAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGG GACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCG GACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGT CCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCC GCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCT GCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT CAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC TCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGC AGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTA CACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTCAGACCCCCACCAAC ACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCAACAACAGCAACCCC AAGCCCAACCCCGCTAGTAAAGCCAAACGGAGAGTAGTTCAGAGGGAAAAAAG AGCCGTCGGTATCGGGGCAATGTTCTTGGGCTTTCTGGGAGCCGCTGGGAGCACG ATGGGGGCGGCCAGCCTTACTCTGACAGTGCAGGCCCGCCAGCTGCTTAGTGGC ATTGTGC AGC AACAGAAC AATCTTCTCAGGGC AATCGAGGCCC AGC AGCACCTC CTGCAGTTGACAGTGTGGGGAATCAAGCAGCTCCAGGCACGAGTCCTGGCTCTG GAGCGCTACTTGCAGGATCAACGGTTCCTTGGAATGTGGGGCTGTAGCGGCAAG CTCATTTGCACAACTGCGGTGCCCTGGAATGCTAGTTGGTCTAACAAGAACCTGT CCCAAATATGGGATAACATGACCTGGATGGAGTGGGAACGAGAAATTTCAAATT ATACCGAGATTATATATTCTTTGATCGAGGAATCACAAAATCAGCAGGAAAAGA ACGAGTTGGACCTCCTCCAACTGGACAAATGGGCTTCCCTGTGGAATTGGTTTAA CATCACCAATTGGCTGTGGTACATCAAGGCTAGCCATCACCATCACCATCACTGA

(SEQ ID NO :46) H chain secreted product IgG4H(underline), flexible linker(bold italics), gp41(bold underline) from HIV-1 BX08 clade B

EIQLQQTGPELVKPGASVKISCKASGYPFTDYIMVWVKQSHGKSLEWIGNISPYYGTT

NYNLKFKGKATLTVDKSSSTAYMOLNSLTSEDSAVYYCARSPNWDGAWFAHWGO

GALVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPC PPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSOEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAK GOPREPOVYTLPPSQEEMTKNOVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPV LDSDGSFFLYSRLTVD SRWOEGNVFSCSVMHEALHNHYTOKSLSLSLGKASOTyr NTISVTPTNNSTPTNNSNPKPNPASKAKRRVVQREKRAVGIGAMFLGFLGAAGST MGAASLTLTVOAROLLSGIVOOONNLLRAIEAQOHLLOLTVWGIKOLOARVLA LERYLQDQRFLGMWGCSGKLICTTAVPWNASWSNKNLSOIWDNMTWMEWER EISNYTEIIYSLIEESQNOOEKNELDLLQLDKWASLWNWFNITNWLWYIKASHH HHHH(SEQ ID NO :47) C2322 [mAnti-DCIR_9E8_H-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-B-6xHis]

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTC CCAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTC AGTCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAG CTGGATTCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGG GATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAG GATACCTCCAGCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATG CTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGG ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACG AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGA GTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGAC AAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTC AGACCCCCACCAACACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCA ACAACAGCAACCCCAAGCCCAACCCCGCTAGTGTATGGAAGGATGCCACTACTA CACTTTTCTGTGCGTCCGACGCCAAAGCCTATGATAAAGAGGTCCACAATGTATG GGCCACACACGCATGTGTGCCCACCGATCCTAATCCTCAAGAAGTTGTCCTGGGG AACGTTACTGAGAATTTCAACATGGGTAAGAATAACATGGTAGAACAGATGCAC GAAGATATTATTTCCCTGTGGGATCAGTCCCTGAAGCCATGCGTGAAGTTGACAC CCCTGTGTGTCACCCTGAATTGCACCGAGCTGAAAAACAGTACCGACACCAATCT GGGTACACAGGAGATGAAGAACTGTTCCTTTAACATTACGACCTCAGTGCGGAA TAAGATGAAACGCGAGTATGCACTCTTTTACAGCCTCGACATTGTTCCCATTGAC AATGACAACACTAGCTATAGGCTGCGGTCATGTAATACATCAATCGTCACGCAA GCCTGCCCTAAGGTCTCTTTCGAACCAATTCCGATTCACTTTTGTGCACCGGCTGG ATTTGCCATTCTGAAGTGTAATAACAAAACTTTTAACGGGACCGGACCCTGCACG AACGTGTCTACAGTGCAGTGCACTCACGGGATTAGACCTGTCGTGTCCACGCAGC TGTTGCTGAACGGGTCACTGGCTGAGGAGGAAGTGGTGATTCGGAGTGAAAATT TCACCAACAATGCCAAGACCATAATCGTGCAACTTAATGAGTCTGTGGAGATAA ACTGTACTAGGCCTAACAATAACACTCGGAAGTCTATACATATTGGGCCCGGCAG AGCTTTCTACACCACTGGCGACATCATCGGCGATATCAGACAAGCTCATTGCAAC ATCAGTCGCACCAATTGGACCAACACCTTGAAGCGCGTGGCGGAAAAGCTTCGA GAGAAATTCAACAATACCACAATCGTCTTCAATCAGTCTAGCGGAGGTGATCCCG AGATAGTTATGCATTCATTTAACTGCGGAGGCGAGTTCTTTTACTGCAATACTAC ACAGCTTTTCAACTCCACCTGGAACGAGACTAACAGCGAAGGC AATATAACATC CGGCACCATCACACTCCCATGCCGCATCAAGCAGATCATCAACATGTGGCAGGA GGTGGGCAAAGCTATGTACGCACCACCAATAGGCGGCCAGATCAAATGCTTGAG TAACATCACAGGCCTCCTCCTGACGAGGGACGGAGGTAGCGATAATAGCAGCAG TGGAAAAGAAATCTTTCGACCAGGGGGGGGTGACATGAGAGACAATTGGAGGA GCGAACTGTACAAGTATAAAGTGGTTATCATTGAGCCTCTCGGAATCGCCCCCAC AGCTAGTAAAGCCAAACGGAGAGTAGTTCAGAGGGAAAAAAGAGCCGTCGGTA TCGGGGCAATGTTCTTGGGCTTTCTGGGAGCCGCTGGGAGCACGATGGGGGCGG CCAGCCTTACTCTGACAGTGCAGGCCCGCCAGCTGCTTAGTGGCATTGTGCAGCA ACAGAACAATCTTCTCAGGGCAATCGAGGCCCAGCAGCACCTCCTGCAGTTGAC AGTGTGGGGAATCAAGCAGCTCCAGGCACGAGTCCTGGCTCTGGAGCGCTACTT GCAGGATCAACGGTTCCTTGGAATGTGGGGCTGTAGCGGCAAGCTCATTTGCACA ACTGCGGTGCCCTGGAATGCTAGTTGGTCTAACAAGAACCTGTCCCAAATATGGG ATAACATGACCTGGATGGAGTGGGAACGAGAAATTTCAAATTATACCGAGATTA TATATTCTTTGATCGAGGAATCACAAAATCAGCAGGAAAAGAACGAGTTGGACC TCCTCCAACTGGACAAATGGGCTTCCCTGTGGAATTGGTTTAACATCACCAATTG GCTGTGGTACATCAAGGCTAGCCATCACCATCACCATCACTGA(SEQ ID NO :48) H chain secreted product IgG4H(underline), flexible \inker(bold italics), gpl40 (bold underline) from HIV-1 BX08 clade B

QVTLKESGPGILQPSOTLSLTCSFSGFSLSTSGMGLSWIROPSGKGLEWLAHIYWDDD RYNPSLKSRLTISKDTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVW GAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVEvSKYGPP CPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTIS AK GQPREPQVYTLPPSOEEMT NQVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPV LDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQ SLSLSLGKASO Pr NTISVTPTNNSTPTNNSNPKPNPASVWKDATT1 LFCASDAKAYOKE\HNYWATH ACVPTDPNPOEVVLGNVTENFNMGKNNMVEOMHEDIISLWDQSLKPCVKLTPL CVTLNCTELK STDTNLGTQEMKNCSFNITTSVRNKM REYALFYSLDIVPIDN DNTSYRLRSCNTSIVTOACPKVSFEPIPIHFCAPAGFAILKCNNKTFNGTGPCTNV STVOCTHGIRPVVSTQLLLNGSLAEEEVVIRSENFTNNAKTHVOLNESVEINCTR PNNNTRKSIHIGPGRAFYTTGDIIGDIROAHCNISRTNWTNTLKRVAEKLREKFN NTTIVFNOSSGGDPEIVMHSFNCGGEFFYCNTTQLFNSTWNETNSEGNITSGTITL PCRIKOIINMWQEVGKAMYAPPIGGOIKCLSNITGLLLTRDGGSDNSSSGKEIFR PGGGDMRDNWRSELY YKVVIIEPLGIAPTASKAKRRVVQRE RAVGIGAMFL GFLGAAGSTMGAASLTLTVOAROLLSGIVOOONNLLRAIEAOOHLLOLTVWGI KOLOARVLALERYLODQRFLGMWGCSGKLICTTAVPWNASWSNKNLSOIWDN MTWMEWEREISNYTEIIYSLIEESONQOEKNELDLLQLDKWASLWNWFNITNW LWYIKASHHHHHH(SEQ ID NO :49) C2865 [hAnti-CD40VH3-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl20-B-6xHis]

ATGGGTTGGAGCCTCATCTTGCTCTTCCTTGTCGCTGTTGCTACGCGTGTCCACTC CGAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCCGGAGGGTCCCT GAAACTCTCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGG TTCGCCAGGCCCCAGGCAAGGGCCTGGAGTGGGTCGCATACATTAATTCTGGTGG TGGTAGCACCTATTATCCAGACACTGTAAAGGGCCGATTCACCATCTCCAGAGAC AATGCCAAGAACACCCTGTACCTGCAAATGAACAGCCTGAGGGCCGAGGACACA GCCGTGTATTACTGTGCAAGACGGGGGTTACCGTTCCATGCTATGGACTATTGGG GTCAAGGAACCCTGGTCACCGTCTCCTCAGCCAAAACGAAGGGCCCATCCGTCTT CCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGC CTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTC CCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACAC CTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTC CAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACC ATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACC CCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAG TTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGG GAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACC AGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCC CGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCAC AGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCC TGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGA GCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCG ACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGG AGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACAC ACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTCAGACCCCCACCAACACC ATCAGCGTGACCCCCACCAACAACAGCACCCCCACCAACAACAGCAACCCCAAG CCCAACCCCGCTAGTGTATGGAAGGATGCCACTACTACACTTTTCTGTGCGTCCG ACGCCAAAGCCTATGATAAAGAGGTCCACAATGTATGGGCCACACACGCATGTG TGCCCACCGATCCTAATCCTCAAGAAGTTGTCCTGGGGAACGTTACTGAGAATTT CAACATGGGTAAGAATAACATGGTAGAACAGATGCACGAAGATATTATTTCCCT GTGGGATCAGTCCCTGAAGCCATGCGTGAAGTTGACACCCCTGTGTGTCACCCTG AATTGCACCGAGCTGAAAAACAGTACCGACACCAATCTGGGTACACAGGAGATG AAGAACTGTTCCTTTAACATTACGACCTCAGTGCGGAATAAGATGAAACGCGAG TATGCACTCTTTTACAGCCTCGACATTGTTCCCATTGACAATGACAACACTAGCT ATAGGCTGCGGTCATGTAATACATCAATCGTCACGCAAGCCTGCCCTAAGGTCTC TTTCGAACCAATTCCGATTCACTTTTGTGCACCGGCTGGATTTGCCATTCTGAAGT GTAATAACAAAACTTTTAACGGGACCGGACCCTGCACGAACGTGTCTACAGTGC AGTGCACTCACGGGATTAGACCTGTCGTGTCCACGCAGCTGTTGCTGAACGGGTC ACTGGCTGAGGAGGAAGTGGTGATTCGGAGTGAAAATTTCACCAACAATGCCAA GACCATAATCGTGCAACTTAATGAGTCTGTGGAGATAAACTGTACTAGGCCTAAC AATAACACTCGGAAGTCTATACATATTGGGCCCGGCAGAGCTTTCTACACCACTG GCGACATCATCGGCGATATCAGACAAGCTCATTGCAACATCAGTCGCACCAATTG GACCAACACCTTGAAGCGCGTGGCGGAAAAGCTTCGAGAGAAATTCAACAATAC CACAATCGTCTTCAATCAGTCTAGCGGAGGTGATCCCGAGATAGTTATGCATTCA TTTAACTGCGGAGGCGAGTTCTTTTACTGCAATACTACACAGCTTTTCAACTCCAC CTGGAACGAGACTAACAGCGAAGGCAATATAACATCCGGCACCATCACACTCCC ATGCCGCATCAAGCAGATCATCAACATGTGGCAGGAGGTGGGCAAAGCTATGTA CGCACCACCAATAGGCGGCCAGATCAAATGCTTGAGTAACATCACAGGCCTCCT CCTGACGAGGGACGGAGGTAGCGATAATAGCAGCAGTGGAAAAGAAATCTTTCG ACCAGGGGGGGGTGACATGAGAGACAATTGGAGGAGCGAACTGTACAAGTATA AAGTGGTTATCATTGAGCCTCTCGGAATCGCCCCCACAGCTAGCCACCATCACCA TCACCATTGA(SEQ ID NO :50)

H chain secreted product IgG4H(underline), flexible linker(Z>o/i/ italics), gpl20 (bold underIine)from HIV-1 BX08 clade B

EVOLVESGGGLVOPGGSLKLSCATSGFTFSDYYMYWVROAPG GLEWVAYI SGG GSTYYPDTV GRFTISRDNAKNTLYLQMNSLRAEDTAVYYCARRGLPFHAMDYWG OGTLVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPA VLOS S GLYSLSS V VTVPS S SLGTKT YTCN VDHKP SNTKVDKRVESKYGPPC PPCPAPEFEGGPSVFLFPP PKDTLMISRTPEVTCVVVDVSOEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLFIQDWLNGKEYKCKVSNKGLPSSIEKTIS AK GQPREPQVYTLPPSOEEMTKNOVSLTCLVKGFYPSDIAVEWESNGOPEN YKTTPPV LDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTOKSLSLSLGKASOr r NTISVTPTNNSTPTNNSNPKPNPASVWKOATTTLFCASOAKAYT)KEVilNVWATll ACVPTDPNPOEVVLGNVTENFNMGKNNMVEOMHEDIISLWDQSLKPCVKLTPL CVTLNCTELKNSTDTNLGTQEMKNCSFNITTSVRNKMKREYALFYSLDIVPIDN DNTSYRLRSCNTSIVTQACPKVSFEPIPIHFCAPAGFAILKCNNKTFNGTGPCTNV STVOCTHGIRPVVSTOLLLNGSLAEEEVVIRSENFTNNA TIIVQLNESVEINCTR PNNNTRKSIHIGPGRAFYTTGDIIGDIRQAHCNISRTNWTNTLKRVAEKLREKFN NTTIVFNOSSGGDPEIVMHSFNCGGEFFYCNTTQLFNST NETNSEGNITSGTITL PCRIKOIINMWOEVGKAMYAPPIGGQI CLSNITGLLLTRDGGSDNSSSGKEIFR PGGGDMRDNWRSELYKYKVVIIEPLGIAPTASHHHHHHiSEQ ID NO :51)

C1804 [mAnti-LOX-115C4H-LV-hIgG4H-C-Flex-vl-gpl40-Z-6xHis]

ATGGGAGGGATCTGGATCTTTCTCTTCCTCCTGTCAGGAACTGCAGGTGCCCACT CTGAGATCCAGCTGCAGCAGACTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAG TGAAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTG GGTGAAGCAGAGCCATGGAAAGAGCCTTGAGTGGATTGGAAATATTAGTCCTTA CTATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAAGGCCACATTGACTGTA GACAAATCTTCCAGCACAGCCTACATGCAGCTCAACAGTCTGACATCTGAGGACT CTGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTGCAGCCAAAACAAAGGGCCCATC CGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTG GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACT CTACTCCCTCAGC AGCGTGGTGACCGTGCCCTCC AGCAGCTTGGGCACGAAGACC TACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTT GAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGG GACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCG GACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGT CCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGC ATAATGCCAAGAC AAAGCC GCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCT GCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT CAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC TCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGC AGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTA CACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGTCAGACCCCCACCAAC ACCATCAGCGTGACCCCCACCAACAACAGCACCCCCACCAACAACAGCAACCCC AAGCCCAACCCCGCTAGTAACCTGTGGGTGACCGTGTACTACGGCGTGCCCGTGT GGAAGGAGGCCAAGACCACCCTGTTCTGCGCCAGCGACGCCAAGAGCTACGAGA AGGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGCCCACCGACCCCAACC CCCAGGAGATCGTGCTGGGCAACGTGACCGAGAACTTCAACATGTGGAAGAACG ACATGGTGGACCAGATGCACGAGGACATCATCAGCCTGTGGGACCAGAGCCTGA AGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGAACTGCACCGAGGTGA ACGTGACCCGCAACGTGAACAACAGCGTGGTGAACAACACCACCAACGTGAACA ACAGCATGAACGGCGACATGAAGAACTGCAGCTTCAACATCACCACCGAGCTGA AGGACAAGAAGAAGAACGTGTACGCCCTGTTCTACAAGCTGGACATCGTGAGCC TGAACGAGACCGACGACAGCGAGACCGGCAACAGCAGCAAGTACTACCGCCTGA TCAACTGCAACACCAGCGCCCTGACCCAGGCCTGCCCCAAGGTGAGCTTCGACCC CATCCCCATCCACTACTGCGCCCCCGCCGGCTACGCCATCCTGAAGTGCAACAAC AAGACCTTCAACGGCACCGGCCCCTGCCACAACGTGAGCACCGTGCAGTGCACC CACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCTGAACGGCAGCCTGGCC GAGGAGGGCATCATCATCCGCAGCGAGAACCTGACCAACAACGTCAAGACCATC ATCGTGCACCTGAACCGCAGCATCGAGATCGTGTGCGTGCGCCCCAACAACAAC ACCCGCCAGAGCATCCGCATCGGCCCCGGCCAGACCTTCTACGCCACCGGCGAC ATCATCGGCGACATCCGCCAGGCCCACTGCAACATCAGCCGCACCAACTGGACC AAGACCCTGCGCGAGGTGCGCAACAAGCTGCGCGAGCACTTCCCCAACAAGAAC ATCACCTTCAAGCCCAGCAGCGGCGGCGACCTGGAGATCACCACCCACAGCTTC AACTGCCGCGGCGAGTTCTTCTACTGCAACACCAGCGGCCTGTTCAGCATCAACT ACACCGAGAACAACACCGACGGCACCCCCATCACCCTGCCCTGCCGCATCCGCC AGATCATCAACATGTGGCAGGAGGTGGGCCGCGCCATGTACGCCCCCCCCATCG AGGGCAACATCGCCTGCAAGAGCGACATCACCGGCCTGCTGCTGGTGCGCGACG GCGGCAGCACCAACGACAGCACCAACAACAACACCGAGATCTTCCGCCCCGCCG GCGGCGACATGCGCGACAACTGGCGCAGCGAGCTGTACAAGTACAAGGTGGTGG AGATCAAGCCCCTGGGCATCGCCCCCACCGAGGCCAAGCGCCGCGTGGTGGAGC GCGAGAAGCGCGCCGTGGGCATCGGCGCCGTGTTCCTGGGCTTCCTGGGCGCCG CCGGCAGCACCATGGGCGCCGCCAGCATCACCCTGACCGCCCAGGCCCGCCAGG TGCTGAGCGGCATCGTGCAGCAGCAGAGCAACCTGCTGCGCGCCATCGAGGCCC AGCAGCACCTGCTGCAGCTGACCGTGTGGGGCATCAAGCAGCTGCAGACCCGCG TGCTGGCCATCGAGCGCTACCTGAAGGACCAGCAGCTGCTGGGCCTGTGGGGCT GCAGCGGCAAGCTGATCTGCACCACCGCCGTGCCCTGGAACATCAGCTGGAGCA ACAAGAGCAAGACCGACATCTGGGACAACATGACCTGGATGCAGTGGGACCGCG AGATCAGCAACTACACCAACACCATCTACCGCCTGCTGGAGGACAGCCAGAGCC AGCAGGAGCAGAACGAGAAGGACCTGCTGGCCCTGGACAGCTGGAACAACCTGT GGAACTGGTTCGACATCACCAAGTGGCTGTGGTACATCAAGGCTAGCCACCATC ACCATCACCATTGA(SEQ ID NO :52)

H chain secreted product IgG4H(underline), flexible nker(bold italics), gpl40 (bold underline) from HIV-196ZM651 (Clade C)

EIOLQQTGPELVKPGASVKISC ASGYPFTDYIMVWVKQSHGKSLEWIGNISPYYGTT NYNLKFKGKATLTVDKSSSTAYMQLNSLTSEDSAVYYCARSPNWDGAWFAHWGQ GALVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPC PPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEY CKVSNKGLPSSIEKTISKAK GQPREPQVYTLPPSQEEMTKNOVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPV LDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMFIEAL INHYTQKSLSLSLG AS07 ^, NTISVTPTNNSTPTNNSNPKPNPASNL\\VT\YYGVYV\VKEAKTTLFCASDAKSYE KEVHNVWATHACVPTDPNPQEIVLGNVTENFNMW NDMVDOMHEDIISLWDO SLKPCVKLTPLCVTLNCTEVNVTRNVNNSVVNNTTNVNNSMNGDMKNCSFNITT ELKDKKKNVYALFYKLDIVSLNETDDSETGNSSKYYRLINCNTSALTQACPKVSF DPIPIHYCAPAGYAILKCNNKTFNGTGPCHNVSTVOCTHGIKPVVSTOLLLNGSL AEEGIIIRSENLTNNVKTIIVHLNRSIEIVCVRPNNNTRQSIRIGPGQTFYATGDIIG DIROAHCNISRTNWTKTLREVRNKLREHFPNKNITFKPSSGGDLEITTHSFNCRG EFFYCNTSGLFSINYTENNTDGTPITLPCRIROIINMWOEVGRAMYAPPIEGNIAC KSDITGLLLVRDGGSTNDSTNNNTEIFRPAGGDMRDNWRSELYKYKVVEIKPLG IAPTEAKRRVVEREKRAVGIGAVFLGFLGAAGSTMGAASITLTAQAROVLSGIV OOOSNLLRAIEAOOHLLOLTVWGIKQLOTRVLAIERYLKDOOLLGLWGCSGKL ICTTAVPWNISWSNKSKTDIWDNMTWMQWDREISNYTNTIYRLLEDSOSOOEQ NEKDLLALDSWNNLWNWFDITKWLWYIKASHFIHHHH(SEO ID NO :53)

C208 [mAnti-DCIR 9E8_K-LV-hIgGK-C]

ATGGAGACAGACACACTCCTGCTATGGGTGCTGCTGCTCTGGGTTCCAGGTTCCA

CAGGTAACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCA

GAGGGCCACCATATCCTGCAGAGCCAGTGAAAGTATTCATAGTTATGGCAATAG TTTTCTGCACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTAT CTTGCATCCAACCTAGAATCTGGGGTCCCTGCCAGGTTCAGCGGCAGTGGGTCTA GGACAGACTTCACCCTCACCATTGATCCTGTGGAGGCTGATGATGCTGCAACCTA TTACTGTCAGCAAAATAATGAGGATCCGTGGACGTTCGGTGGAGGCACCAAGCT CGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATC CCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACT CCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCA GCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCG AAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG(SEQ ID NO :54)

L chain secreted product mouse V region(underline) - human C regionfbold underline) to pair with mAnti-DCIR_9E8_H-LV-hIgG4H-C-based fusion proteins

NIVLTOSPASLAVSLGORATISCRASESIHSYGNSFLHWYQQKPGOPPKLLIYLASNLE SGVPARFSGSGSRTDFTLTIDPVEADDAATYYCOQN EDPWTFGGGTKLEIKRTVA APSVFIFPPSDEQL SGTASVVCLLNNFYPREAKVOWKVDNALOSGNSOESVTE ODS DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEO ID NO :55)

C2269 [hAnti-DCIRVK4-LV-hIgGK-C]

ATGAGGGTCCCCGCTCAGCTCCTGGGGCTCCTGCTGCTCTGGCTCCCAGGCGCGC GATGTGACATTGTGATGACCCAATCTCCAGACTCTTTGGCTGTGTCTCTAGGGGA GAGGGCCACC ATAAACTGCAGAGCCAGTGAAAGTATTCATAGTTATGGCAATAG TTTTCTGCACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTAT CTTGCATCCAACCTAGAATCTGGGGTCCCTAGCAGGTTCAGCGGCAGTGGGTCTA GGACAGACTTCACCCTCACCATTAGCAGCCTGCAGCCTGAGGATTTCGCAACCTA TTACTGTCAGCAAAATAATGAGGACCCGTGGACGTTCGGTCAGGGCACCAAGCT CGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATC CCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACT CCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCA GCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCG AAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG(SEQ ID NO :56)

L chain secreted product to pair with hAnti-DCIRVHl-LV-hIgG4H-C-based fusion proteins

DIV TQSPDSLAVSLGERATINCPvASESIHSYGNSFLHWYQQKPGQPPKLLIYLASNL ESGVPSRFSGSGSRTDFTLTISSLQPEDFATYYCQQNNEDPWTFGQGTKLEIKRTVAA PSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEQ ID NO :57) C2128 [hAnti-CD40VK2-LV-hIgGK-C]

ATGAGGGTCCCCGCTCAGCTCCTGGGGCTCCTGCTGCTCTGGCTCCCAGGCGCGC GATGTGATATCCAGATGACACAGAGCCCTTCCTCCCTGTCTGCCTCTGTGGGAGA CAGAGTCACCATCACCTGCAGTGCAAGTCAGGGCATTAGCAATTATTTAAACTGG TATCAGCAGAAACCAGGCAAGGCCGTTAAACTCCTGATCTATTACACATCAATTT TACACTCAGGAGTCCCATCAAGGTTCAGTGGCAGTGGGTCTGGGACAGATTATAC CCTCACCATCAGCTCCCTGCAGCCTGAAGATTTCGCCACTTACTATTGTCAGCAG TTTAATAAGCTTCCTCCGACGTTCGGTGGAGGCACCAAACTCGAGATCAAACGAA CTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCT GGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAG TACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCA CAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGA GCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGG GCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG(SEQ ID NO :58)

L chain secreted product to pair with hAnti-CD40VH3-LV-hIgG4H-C-based fusion proteins

DIQMTQSPSSLSASVGDRVTITCSASQGISNYLNWYQQKPGKAVKLLIYYTSILHSGV PSRFSGSGSGTDYTLTISSLQPEDFATYYCQQFN LPPTFGGGTKLEIKRTVAAPSVFIF PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLS ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEQ ID NO :59)

CI 15 [mAnti-LOX-115C4K-LV-hIgGK-C]

ATGGAGACAGACACAATCCTGCTATGGGTGCTGCTGCTCTGGGTTCCAGGCTCCA CTGGTGACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAG AGGGCCACCATCTCCTGCAAGGCCAGCCAAAGTGTTGATTATGATGGTGATAGTT ATATGAACTGGTTCCAACAGAAACCAGGACAGCCACCCAAACTCCTCATCTATGC TGCATCCAATCTAGAATCTGGGATCCCAGCCAGGTTTAGTGGCAGTGGGTCTGGG ACAGACTTCACCCTCAACATCCATCCTGTGGAGGAGGAGGATGCTGCAACCTATT ACTGTCAGCAAAGTAATGAGGATCCATTCACGTTCGGCTCGGGGACAAAGCTCG AGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGA GCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCC AGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCC CAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAG CACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGA AGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGA GTGTTAG(SEQ ID NO :60)

L chain secreted product mouse V region(underline) - human C region bold underline) to pair with mAnti-LOX-115C4H-LV-hIgG4H-C-based fusion proteins

DIVLTOSPASLAVSLGQRATISCKASQSVDYDGDSYMNWFQQKPGOPPKLLIYAASN LESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPFTFGSGT LEIKRTVA APSVFIFPPSDEOLKSGTASVVCLLNNFYPREAKVQWKVDNALOSGNSOESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEQ ID NO :61)

C2266 [hAnti-LOX-lVKl-LV-hlgGK-C]

ATGAGGGTCCCCGCTCAGCTCCTGGGGCTCCTGCTGCTCTGGCTCCCAGGCGCGC GATGTGACATTGTGCTGACCCAATCTCCAGACTCTTTGGCTGTGTCTCTAGGGGA GAGGGCCACCATCAACTGCAAGGCCAGCCAAAGTGTTGATTATGATGGTGATAG TTATATGAACTGGTTCCAACAGAAACCAGGACAGCCACCCAAACTCCTCATCTAT GCTGCATCCAATCTAGAATCTGGCATCCCAGCCAGGTTTAGTGGCAGTGGGTCTG GGACAGACTTCACCCTCACCATCAACAGCCTGGAGGAGGAGGATGCTGCAACCT ATTACTGTCAGCAAAGTAATGAGGACCCATTCACGTTCGGCCAGGGGACAAAGC TCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGA TGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTAT CCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAAC TCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGC AGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGC GAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG(SEQ ID NO :62) L chain secreted product to pair with hAnti-LOX-lVH3-LV-hIgG4H-C-based fusion proteins

DIVLTQSPDSLAVSLGERATINCKASQSVDYDGDSYMNWFQQKPGQPPKLLIYAASN LESGIPARFSGSGSGTDFTLTINSLEEEDAATYYCQQSNEDPFTFGQGTKLEIKRTVAA PSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEQ ID NO :63)

C2267 [hAnti-LOX-lVK2-LV-hIgGK-C]

ATGAGGGTCCCCGCTCAGCTCCTGGGGCTCCTGCTGCTCTGGCTCCCAGGCGCGC GATGTGACATTGTGCTGACCCAATCTCCAGACTCTTTGGCTGTGTCTCTAGGGGA GAGGGCCACCATCAACTGCAAGGCCAGCCAAAGTGTTGATTATGATGGTGATAG TTATATGAACTGGTTCCAACAGAAACCAGGACAGCCACCCAAACTCCTCATCTAT GCTGCATCCAATCTAGAATCTGGCATCCCAGCCAGGTTTAGTGGCAGTGGGTCTG GGACAGACTTCACCCTCACCATCAACAGCCTGGAGCCTGAGGATTTCGCAACCTA TTACTGTCAGCAAAGTAATGAGGACCCATTCACGTTCGGCCAGGGGACAAAGCT CGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATC CCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACT CCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCA GCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCG AAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG(SEQ ID NO :64) L chain secreted product to pair with hAnti-LOX- 1 VH7-LV-hIgG4H-C-based fusion proteins

DIVLTQSPDSLAVSLGERATINCKASQSVDYDGDSYMNWFQQKPGQPPKLLIYAASN

LESGIPARFSGSGSGTDFTLTINSLEPEDFATYYCQQSNEDPFTFGQGTKLEI RTVAA PSVFIFPPSDEQLKSGTASVVCLLN FYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLS ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEQ ID NO :65)

C2890 [SLAML-6xHis-CthermoCohesin-ViraIenvHIV-gpl20-Z-6xHis]

ATGGATCCCAAAGGATCCCTTTCCTGGAGAATACTTCTGTTTCTCTCCCTGGCTTT TGAGTTGAGCTACGGACTCGACATCACATCCCACCATCACCATCACCATGACGAT CTGGATGCAGTAAGGATTAAAGTGGACACAGTAAATGCAAAACCGGGAGACACA GTAAGAATACCTGTAAGATTCAGCGGTATACCATCCAAGGGAATAGCAAACTGT GACTTTGTATACAGCTATGACCCGAATGTACTTGAGATAATAGAGATAGAACCG GGAGACATAATAGTTGACCCGAATCCTGACAAGAGCTTTGATACTGCAGTATATC CTGACAGAAAGATAATAGTATTCCTGTTTGCAGAAGACAGCGGAACAGGAGCGT ATGCAATAACTAAAGACGGAGTATTTGCTACGATAGTAGCGAAAGTAAAAGAAG GAGCACCTAACGGACTCAGTGTAATCAAATTTGTAGAAGTAGGCGGATTTGCGA ACAATGACCTTGTAGAACAGAAGACACAGTTCTTTGACGGTGGAGTAAATGTTG GAGATACAACAGAACCTGCAACACCTACAACACCTGTAACAACACCGACAACAA CAGATGATCTGGATGCAGCTAGTAACCTGTGGGTGACCGTGTACTACGGCGTGCC CGTGTGGAAGGAGGCCAAGACCACCCTGTTCTGCGCCAGCGACGCCAAGAGCTA CGAGAAGGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGCCCACCGACCC CAACCCCCAGGAGATCGTGCTGGGCAACGTGACCGAGAACTTCAACATGTGGAA GAACGACATGGTGGACCAGATGCACGAGGACATCATCAGCCTGTGGGACCAGAG CCTGAAGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGAACTGCACCGAG GTGAACGTGACCCGCAACGTGAACAACAGCGTGGTGAACAACACCACCAACGTG AACAACAGCATGAACGGCGACATGAAGAACTGCAGCTTCAACATCACCACCGAG CTGAAGGACAAGAAGAAGAACGTGTACGCCCTGTTCTACAAGCTGGACATCGTG AGCCTGAACGAGACCGACGACAGCGAGACCGGCAACAGCAGCAAGTACTACCG CCTGATCAACTGCAACACCAGCGCCCTGACCCAGGCCTGCCCCAAGGTGAGCTTC GACCCCATCCCCATCCACTACTGCGCCCCCGCCGGCTACGCCATCCTGAAGTGCA ACAACAAGACCTTCAACGGCACCGGCCCCTGCCACAACGTGAGCACCGTGCAGT GCACCCACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCTGAACGGCAGCC TGGCCGAGGAGGGCATCATCATCCGCAGCGAGAACCTGACCAACAACGTCAAGA CCATCATCGTGCACCTGAACCGCAGCATCGAGATCGTGTGCGTGCGCCCCAACAA CAACACCCGCCAGAGCATCCGCATCGGCCCCGGCCAGACCTTCTACGCCACCGG CGACATCATCGGCGACATCCGCCAGGCCCACTGCAACATCAGCCGCACCAACTG GACCAAGACCCTGCGCGAGGTGCGCAACAAGCTGCGCGAGCACTTCCCCAACAA GAACATCACCTTCAAGCCCAGCAGCGGCGGCGACCTGGAGATCACCACCCACAG CTTCAACTGCCGCGGCGAGTTCTTCTACTGCAACACCAGCGGCCTGTTCAGCATC AACTACACCGAGAACAACACCGACGGCACCCCCATCACCCTGCCCTGCCGCATC CGCCAGATCATCAACATGTGGCAGGAGGTGGGCCGCGCCATGTACGCCCCCCCC ATCGAGGGCAACATCGCCTGCAAGAGCGACATCACCGGCCTGCTGCTGGTGCGC GACGGCGGCAGCACCAACGACAGCACCAACAACAACACCGAGATCTTCCGCCCC GCCGGCGGCGACATGCGCGACAACTGGCGCAGCGAGCTGTAC AAGTACAAGGTG GTGGAGATCAAGCCCCTGGGCATCGCCCCCACCGAGGCCAAGCGCCGCGTGGTG GAGCGCGAGAAGCGCGCTAGCCACCATCACCATCACCATTGA(SEQ ID NO :66) Secreted product cohesin(underline), gpl20(bold underline) from HIV-196ZM651 (Clade C)

LDITSHHHHHHDDLDAVRIKVDTVNAKPGDTVRIPVRFSGIPSKGIANCDFVYSYDPN VLEHEIEPGDIIVDPNPDKSFDTAVYPDRKIIVFLFAEDSGTGAYAITKDGVFATIVAK VKEGAPNGLSVIKFVEVGGFANNDLVEOKTQFFDGGVNVGDTTEPATPTTPVTTPTT TDDLDAASNLWVTVYYGVPVWKEAKTTLFCASDAKSYEKEVHNVWATHACVP TDPNPOEIVLGNVTENFNMWKNDMVDQMHEDIISLWDOSLKPCVKLTPLCVTL NCTEVNVTRNVNNSVVNNTTNVNNSMNGDM NCSFNITTELKDKKK VYALFY KLDIVSLNETDDSETGNSSKYYRLINCNTSALTQACPKVSFDPIPIHYCAPAGYAI LKCNNKTFNGTGPCHNVSTVOCTHGIKPVVSTQLLLNGSLAEEGIIIRSENLTNN VKTIIVHLNRSIEIVCVRPNNNTROSIRIGPGOTFYATGDIIGDIROAHCNISRTNW TKTLREVRNKLREHFPNKNITFKPSSGGDLEITTHSFNCRGEFFYCNTSGLFSINY TENNTDGTPITLPCRIROIINMWOEVGRAMYAPPIEGNIACKSDITGLLLVRDGG STNDSTNNNTEIFRPAGGDMRDNWRSELYKYKVVEIKPLGIAPTEAKRRVVERE KRASHHHHHHfSEQ ID NO :67)

C2891 [SLAML-6xHis-CthermoCohesin-ViralenvHIV-gpl40-Z-6xHis]

ATGGATCCCAAAGGATCCCTTTCCTGGAGAATACTTCTGTTTCTCTCCCTGGCTTT TGAGTTGAGCTACGGACTCGACATCACATCCCACCATCACCATCACCATGACGAT CTGGATGCAGTAAGGATTAAAGTGGACACAGTAAATGCAAAACCGGGAGACACA GTAAGAATACCTGTAAGATTCAGCGGTATACCATCCAAGGGAATAGCAAACTGT GACTTTGTATACAGCTATGACCCGAATGTACTTGAGATAATAGAGATAGAACCG GGAGACATAATAGTTGACCCGAATCCTGACAAGAGCTTTGATACTGCAGTATATC CTGACAGAAAGATAATAGTATTCCTGTTTGCAGAAGACAGCGGAACAGGAGCGT ATGCAATAACTAAAGACGGAGTATTTGCTACGATAGTAGCGAAAGTAAAAGAAG GAGCACCTAACGGACTCAGTGTAATCAAATTTGTAGAAGTAGGCGGATTTGCGA ACAATGACCTTGTAGAACAGAAGACACAGTTCTTTGACGGTGGAGTAAATGTTG GAGATACAACAGAACCTGCAACACCTACAACACCTGTAACAACACCGACAACAA CAGATGATCTGGATGCAGCTAGTAACCTGTGGGTGACCGTGTACTACGGCGTGCC CGTGTGGAAGGAGGCCAAGACCACCCTGTTCTGCGCCAGCGACGCCAAGAGCTA CGAGAAGGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGCCCACCGACCC CAACCCCCAGGAGATCGTGCTGGGCAACGTGACCGAGAACTTCAACATGTGGAA GAACGACATGGTGGACCAGATGCACGAGGACATCATCAGCCTGTGGGACCAGAG CCTGAAGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGAACTGCACCGAG GTGAACGTGACCCGCAACGTGAACAACAGCGTGGTGAACAACACCACCAACGTG AACAACAGCATGAACGGCGACATGAAGAACTGCAGCTTCAACATCACCACCGAG CTGAAGGACAAGAAGAAGAACGTGTACGCCCTGTTCTACAAGCTGGACATCGTG AGCCTGAACGAGACCGACGACAGCGAGACCGGCAACAGCAGCAAGTACTACCG CCTGATCAACTGCAACACCAGCGCCCTGACCCAGGCCTGCCCCAAGGTGAGCTTC GACCCCATCCCCATCCACTACTGCGCCCCCGCCGGCTACGCCATCCTGAAGTGCA ACAACAAGACCTTCAACGGCACCGGCCCCTGCCACAACGTGAGCACCGTGCAGT GCACCCACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCTGAACGGCAGCC TGGCCGAGGAGGGCATCATCATCCGCAGCGAGAACCTGACCAACAACGTCAAGA CCATCATCGTGCACCTGAACCGCAGCATCGAGATCGTGTGCGTGCGCCCCAACAA CAACACCCGCCAGAGCATCCGCATCGGCCCCGGCCAGACCTTCTACGCCACCGG CGACATCATCGGCGACATCCGCCAGGCCCACTGCAACATCAGCCGCACCAACTG GACCAAGACCCTGCGCGAGGTGCGCAACAAGCTGCGCGAGCACTTCCCCAACAA GAACATCACCTTCAAGCCCAGCAGCGGCGGCGACCTGGAGATCACCACCCACAG CTTCAACTGCCGCGGCGAGTTCTTCTACTGCAACACCAGCGGCCTGTTCAGCATC AACTACACCGAGAACAACACCGACGGCACCCCCATCACCCTGCCCTGCCGCATC CGCCAGATCATCAACATGTGGCAGGAGGTGGGCCGCGCCATGTACGCCCCCCCC ATCGAGGGCAACATCGCCTGCAAGAGCGACATCACCGGCCTGCTGCTGGTGCGC GACGGCGGCAGCACCAACGACAGCACCAACAACAACACCGAGATCTTCCGCCCC GCCGGCGGCGACATGCGCGACAACTGGCGCAGCGAGCTGTACAAGTACAAGGTG GTGGAGATCAAGCCCCTGGGCATCGCCCCCACCGAGGCCAAGCGCCGCGTGGTG GAGCGCGAGAAGCGCGCCGTGGGCATCGGCGCCGTGTTCCTGGGCTTCCTGGGC GCCGCCGGCAGCACCATGGGCGCCGCCAGCATCACCCTGACCGCCCAGGCCCGC CAGGTGCTGAGCGGCATCGTGCAGCAGCAGAGCAACCTGCTGCGCGCCATCGAG GCCCAGCAGCACCTGCTGCAGCTGACCGTGTGGGGCATCAAGCAGCTGCAGACC CGCGTGCTGGCCATCGAGCGCTACCTGAAGGACCAGCAGCTGCTGGGCCTGTGG GGCTGCAGCGGCAAGCTGATCTGCACCACCGCCGTGCCCTGGAACATCAGCTGG AGCAACAAGAGCAAGACCGACATCTGGGACAACATGACCTGGATGCAGTGGGAC CGCGAGATCAGCAACTACACCAACACCATCTACCGCCTGCTGGAGGACAGCCAG AGCCAGCAGGAGCAGAACGAGAAGGACCTGCTGGCCCTGGACAGCTGGAACAA CCTGTGGAACTGGTTCGACATCACCAAGTGGCTGTGGTACATCAAGGCTAGCCAC CATCACCATCACCATTGA(SEQ ID NO :68) Secreted product cohesin(underline), gpl40(bold underline) from HIV-196ZM651 (Clade C)

LDITSHHHHHHDDLDAVRIKVDTVNAKPGDTVRIPVRFSGIPSKGIANCDFVYSYDPN VLEIIEIEPGDIIVDPNPDKSFDTAVYPDRKIIVFLFAEDSGTGAYAITKDGVFATIVAK VKEGAPNGLSVIKFVEVGGFANNDLVEOKTQFFDGGVNVGDTTEPATPTTPVTTPTT TDDLDAASNLWVTVYYGVPVWKEAKTTLFCASDAKSYEKEVHNVWATHACVP TDPNPOEIVLGNVTENFNMWKNDMVDOMHEDHSLWDQSLKPCVKLTPLCVTL NCTEVNVTRNVNNSVVNNTTNVNNSMNGDMKNCSFNITTELKDKK NVYALFY KLDIVSLNETDDSETGNSSKYYRLINCNTSALTQACPKVSFDPIPIHYCAPAGYAI LKCNNKTFNGTGPCHNVSTVQCTHGIKPVVSTOLLLNGSLAEEGIHRSENLTNN VKTIIVHLNRSIEIVCVRPNNNTROSIRIGPGOTFYATGDIIGDIROAHCNISRTNW TKTLREVRNKLREHFPNKNITFKPSSGGDLEITTHSFNCRGEFFYCNTSGLFSINY TENNTDGTPITLPCRIROIINMWQEVGRAMYAPPIEGNIACKSDITGLLLVRDGG STNDSTNNNTEIFRPAGGDMRDNWRSELYKYKVVEIKPLGIAPTEAKRRVVERE KRAVGIGAVFLGFLGAAGSTMGAASITLTAOAROVLSGIVQOOSNLLRAIEAOO HLLOLTVWGIKOLOTRVLAIERYLKDOQLLGLWGCSGKLICTTAVPWNIS SN KSKTDIWDNMTWMOWDREISNYTNTIYRLLEDSOSOOEQNEKDLLALDSWNN LWNWFDITKWLWYIKASHHHHHHiSEQ ID NO :69) C2892 [SLAML-6xHis-CthermoCohesin-ViralenvHIV-gpl40-Z-del-6xHis]

ATGGATCCCAAAGGATCCCTTTCCTGGAGAATACTTCTGTTTCTCTCCCTGGCTTT TGAGTTGAGCTACGGACTCGACATCACATCCCACCATCACCATCACCATGACGAT CTGGATGCAGTAAGGATTAAAGTGGACACAGTAAATGCAAAACCGGGAGACACA GTAAGAATACCTGTAAGATTCAGCGGTATACCATCCAAGGGAATAGCAAACTGT GACTTTGTATACAGCTATGACCCGAATGTACTTGAGATAATAGAGATAGAACCG GGAGACATAATAGTTGACCCGAATCCTGACAAGAGCTTTGATACTGCAGTATATC CTGACAGAAAGATAATAGTATTCCTGTTTGCAGAAGACAGCGGAACAGGAGCGT ATGCAATAACTAAAGACGGAGTATTTGCTACGATAGTAGCGAAAGTAAAAGAAG GAGCACCTAACGGACTCAGTGTAATCAAATTTGTAGAAGTAGGCGGATTTGCGA ACAATGACCTTGTAGAACAGAAGACACAGTTCTTTGACGGTGGAGTAAATGTTG GAGATACAACAGAACCTGCAACACCTACAACACCTGTAACAACACCGACAACAA CAGATGATCTGGATGCAGCTAGTAACCTGTGGGTGACCGTGTACTACGGCGTGCC CGTGTGGAAGGAGGCCAAGACCACCCTGTTCTGCGCCAGCGACGCCAAGAGCTA CGAGAAGGAGGTGCACAACGTGTGGGCCACCCACGCCTGCGTGCCCACCGACCC CAACCCCCAGGAGATCGTGCTGGGCAACGTGACCGAGAACTTCAACATGTGGAA GAACGACATGGTGGACCAGATGCACGAGGACATCATCAGCCTGTGGGACCAGAG CCTGAAGCCCTGCGTGAAGCTGACCCCCCTGTGCGTGACCCTGAACTGCACCGAG GTGAACGTGACCCGCAACGTGAACAACAGCGTGGTGAACAACACCACCAACGTG AACAACAGCATGAACGGCGACATGAAGAACTGCAGCTTCAACATCACCACCGAG CTGAAGGACAAGAAGAAGAACGTGTACGCCCTGTTCTACAAGCTGGACATCGTG AGCCTGAACGAGACCGACGACAGCGAGACCGGCAACAGCAGCAAGTACTACCG CCTGATCAACTGCAACACCAGCGCCCTGACCCAGGCCTGCCCCAAGGTGAGCTTC GACCCCATCCCCATCCACTACTGCGCCCCCGCCGGCTACGCCATCCTGAAGTGCA ACAACAAGACCTTCAACGGCACCGGCCCCTGCCACAACGTGAGCACCGTGCAGT GCACCCACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCTGAACGGCAGCC TGGCCGAGGAGGGCATCATCATCCGCAGCGAGAACCTGACCAACAACGTCAAGA CCATCATCGTGCACCTGAACCGCAGCATCGAGATCGTGTGCGTGCGCCCCAACAA CAACACCCGCCAGAGCATCCGCATCGGCCCCGGCCAGACCTTCTACGCCACCGG CGACATCATCGGCGACATCCGCCAGGCCCACTGCAACATCAGCCGCACCAACTG GACCAAGACCCTGCGCGAGGTGCGCAACAAGCTGCGCGAGCACTTCCCCAACAA GAACATCACCTTCAAGCCCAGCAGCGGCGGCGACCTGGAGATCACCACCCACAG CTTCAACTGCCGCGGCGAGTTCTTCTACTGCAACACCAGCGGCCTGTTCAGCATC AACTACACCGAGAACAACACCGACGGCACCCCCATCACCCTGCCCTGCCGCATC CGCCAGATCATCAACATGTGGCAGGAGGTGGGCCGCGCCATGTACGCCCCCCCC ATCGAGGGCAACATCGCCTGCAAGAGCGACATCACCGGCCTGCTGCTGGTGCGC GACGGCGGCAGCACCAACGACAGCACCAACAACAACACCGAGATCTTCCGCCCC GCCGGCGGCGACATGCGCGACAACTGGCGCAGCGAGCTGTACAAGTACAAGGTG GTGGAGATCAAGCCCCTGGGCATCGCCCCCACCGAGGCCAAGCGCCGCGTGGTG GAGCGCGAGAAGCGCGCCGTGGGCATCGGCGCCGTGTTCCTGGGCTTCCTGGGC GCCGCCGGCAGCACCATGGGCGCCGCCAGCATCACCCTGACCGCCCAGGCCCGC CAGGTGCTGAGCGGCATCGTGCAGCAGCAGAGCAACCTGCTGCGCGCCATCGAG GCCCAGCAGCACCTGCTGCAGCTGACCGTGTGGGGCATCAAGCAGCTGCAGACC CGCGTGCTGGCCATCGAGCGCTACCTGAAGGACCAGCAGCTGCTGGGCCTGTGG GGCTGCAGCGGCAAGCTGATCTGCACCACCGCCGTGCCCTGGAACATCAGCTGG AGCAACAAGAGCAAGACCGACATCTGGGACAACATGACCTGGATGCAGTGGGAC CGCGAGATCAGCAACTACACCAACACCATCTACCGCCTGCTGGAGGACAGCCAG AGCCAGCAGGAGCAGAACGAGAAGGACCTGCTGGCTAGCCACCATCACCATCAC CATTGA(SEQ ID NO :70) Secreted product cohesin (underline), gpl40 del (bold underline) from HIV-196ZM651 (Clade C)

LDITSHHHHHHDDLDAVRI VDTVNAKPGDTVRIPVFSGIPSKGIANCDFVYSYDPNV

LEIIEIEPGDIIVDPNPDKSFDTAVYPDRKIIVFLFAEDSGTGAYAITKDGVFATIVAKV KEGAPNGLSVIKFVEVGGFANNDLVEOKTOFFDGGVNVGDTTEPATPTTPVTTPTTT DDLDAASNLWVTVYYGVPVWKEAKTTLFCASDAKSYEKEVHNVWATHACVPT

DPNPOEIVLGNVTENFNMWKNDMVDOMHEDIISLWDQSLKPCVKLTPLCVTLN CTEVNVTRNVNNSVVNNTTNVNNSMNGDMKNCSFNITTELKD KKNVYALFYK LDIVSLNETDDSETGNSSKYYRLINCNTSALTQACPKVSFDPIPIHYCAPAGYAIL KCNNKTFNGTGPCHNVSTVOCTHGIKPVVSTQLLLNGSLAEEGIIIRSENLTNNV KTIIVHLNRSIEIVCVRPNNNTROSIRIGPGOTFYATGDIIGDIROAHCNISRTNWT KTLREVRNKLREHFPNKNITFKPSSGGDLEITTHSFNCRGEFFYCNTSGLFSINYT ENNTDGTPITLPCRIROIINMWOEVGRAMYAPPIEGNIACKSDITGLLLVRDGGS TNDSTNNNTEIFRPAGGDMRDNWRSELYKYKVVEIKPLGIAPTEAKRRVVEREK RAVGIGAVFLGFLGAAGSTMGAASITLTAQAROVLSGIVOOOSNLLRAIEAOOH LLOLTVWGIKOLOTRVLAIERYLKDOOLLGLWGCSGKLICTTAVPWNISWSNK SKTDIWDNMTVVMQWDREISNYTNTIYRLLEDSOSOOEQNEKDLLASHHHHHHIS EQ ID NO :71)

[00205] Constructs that have been expressed as proteins are listed in Table 1.

Table 1.

Expressed ENV fusion proteins

Mam-cetHS-puro[SLAML-6xHis-Ctherm^

Mam-cetHS-pun)|SLAML-6xHis-CthernioCohesin-F)ex-vl-ViralenvHlV-gp41-B-6xI lis]

Maiii-cetHS-puro[SLAML-6xJrIis-CthermoCohesin-ViraIenvHlV-gpl.20-Z-6xHis]

Mam-cctHS-puro[SLAML-6xHis-CthermoCohcsin-ViralenvHIV-gpl40-Z-6xUis]

Maiu-cetHS-puiO|SLAML-6xHis-CtherinoCohesin-ViralenvHIV-gpl40-Z-del-6xHis|

IV1am-cetHS-pnro[SLAMi_^6xHis-CthcrmoCohesiii-ViralcnvHlV-gp4]-Z-6xHi8]

Mam-cctllS-piiro[SLAML-ViraienvlIIV-gpl40-B-GCN4-6xHis-Avitag]

rAB-cetHS-puro[hAnti-CD40VH3-LV-hI_gG4H-C-Flex-vl-ViralenvH rAB-

cetHS-puro[hAnti-CD40VK2-LV-hIgGK-C]

rAB-cetHS-puroihAnh-DCIRVHl-LV-hlgG4H-C-Flex-vl-ViralenvHIV-gpl40-C-6xHis] rAB- cetHS-purolliAnti-DCIRVK4-LV-hIgGK-CJ

rAB-cetHS-puro[hAnti-DCIRVHl-LV-hIgG4H-C-Flex-vl-ViralenvHIV-gpl40-S-6xHis] rAB- cetHS-puro[hAnti-DCIRVK4-LV-hIgGK-C] i K \

rAB-cetHS-puro[mIgG2bH-ViralenvSIV-gpl20-6xHis] rAB-cetHS-puro[mIgG2bKl

For SEQ ID NOs 72 - 91 CDR nucleotide and protein sequences are underlined. CDR definitions according to Kabat Anti-LOX VHI Heavy Chain Sequences

GAGATCCAGCTGGTGCAGAGCGGACCTGAGCTGAAGAAGCCTGGGGCTTCAGTG AAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGGG TGAAGCAGGCCCATGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTACT ATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACATTGACTGTAG AC AAATCTACCAGCACAGCCTAC ATGGAGCTC AAC AGTCTGAGATCTGAGGACT CTGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTAGC(SEQ ID NO :72)

EIQLVQSGPELKKPGASVKISCKASGYPFT D Y IM V W V K Q A H GKGLEWIG NISPYYGTTNYNLKFKGRA TLTVDKSTSTAYME LNSLRSEDSAVYYCAR SPN WDGAWFAHW GQGALVTVS

S(SEQ ID NO:73)

Anti-LOX VH2 Heavy Chain Sequences

GAGATCCAGCTGGTGCAGAGCGGAAGCGAGCTGAAGAAGCCTGGGGCTTCAGTG AAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGGG TGAAGCAGGCCCATGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTACT ATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACATTGACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAGCAGTCTGAGATCTGAGGACA CCGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTAGC(SEQ ID NO:74)

EIQLVQSGSELKKPGASVKISCKASGYPFT D YIMVW V K Q A H G K G L E W I G NISPYYGTTNYNLKFKGR ATLTVD STSTAYME LSSLRSEDTAVYYCAR SPN WDGAWFAHW GQGALVTVS S(SEQ ID NO:75)

Anti-LOX VH3 Heavy Chain Sequences

GAGATCCAGCTGGTGCAGAGCGGAAGCGAGCTGAAGAAGCCTGGGGCTTCAGTG AAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGGG TGAGGCAGGCCCCTGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTACT ATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACATTGACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAGCAGTCTGAGATCTGAGGACA CCGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTAGC(SEQ ID NO :76)

EIQLVQSGSELKKPGASVKISCKASGYPFT D YIMVW V R Q A P G K G L E W I G NISPYYGTTNYNLKFKGR ATLTVDKSTSTAYME LSSLRSEDTAVYYCAR SPN WDGAWFAHW GQGALVTVS S(SEQ ID NO:77)

Anti-LOX VH4 Heavy Chain Sequences

GAGATCCAGCTGGTGCAGAGCGGAAGCGAGCTGAAGAAGCCTGGGGCTTCAGTG AAGGTGTCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGGG TGAGGCAGGCCCCTGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTACT ATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACAATCACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAGCAGTCTGAGATCTGAGGACA CCGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTAGC(SEQ ID NO :78)

EIQLVQSGSELKKPGASV VSCKASGYPFT D YIMV W V R Q A P G K G L E W I G NISPYYGTTNYNLKFKGR ATITVDKSTSTAYME LSSLRSEDTAVYYCAR SPNWDGA WFAHW GQGALVTVS S(SEQ IDNO:79)

Anti-LOX VH5 Heavy Chain Sequences

CAGATCCAGCTGGTGCAGAGCGGAAGCGAGCTGAAGAAGCCTGGGGCTTCAGTG AAGGTGTCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGGG TGAGGCAGGCCCCTGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTACT ATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGTGACAATCACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAGCAGTCTGAGATCTGAGGACA CCGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGGCTCTGGTCACTGTCTCTAGC(SEQ ID NO :80)

QIQLVQSGSELKKPGASVKVSCKASGYPFT D Y I M V W V R Q A P G K G L E W I G NISPYYGTTNYNLKFKGR VTITVDKSTSTAYME LSSLRSEDTAVYYCAR SPN WDGA WFAH W GQGALVTVS S(SEQ ID NO:81)

Anti-LOX VH6 Heavy Chain Sequences

GAGATCCAGCTGGTGCAGAGCGGACCTGAGCTGAAGAAGCCTGGGGCTTCAGTG AAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGGG TGAAGCAGGCCCATGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTACT ATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACATTGACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAACAGTCTGAGATCTGAGGACT CTGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGACCCTGGTCACTGTCTCTAGC(SEQ ID NO :82) EIQLVQSGPEL PGASVKISCKASGYPFT D YIMV W V K Q A H G K G L E W I G N1SPYYGTTNYNLKFKGR ATLTVDKSTSTAYME LNSLRSEDSAVYYCAR SPN WDGAWFAH W GQGTLVTVS S(SEQ ID NO :83)

Anti-LOX VH7 Heavy Chain Sequences

GAGATCCAGCTGGTGCAGAGCGGAAGCGAGCTGAAGAAGCCTGGGGCTTCAGTG AAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGGG TGAAGCAGGCCCATGGAAAGGGCCTTGAGTGGATTGGAAACATTAGTCCTTACT ATGGTACTACTAACTACAATCTGAAGTTCAAGGGCAGGGCCACATTGACTGTAG ACAAATCTACCAGCACAGCCTACATGGAGCTCAGCAGTCTGAGATCTGAGGACA CCGCAGTCTATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCA CTGGGGCCAAGGGACCCTGGTCACTGTCTCTAGC(SEQ ID NO :84) EIQLVOSGSELKKPGASVKISCKASGYPFTDYIMVWVKOAH G K G L E W I G NISPYYGTTNYNL FKGR ATLTVDKSTSTAYME LSSLRSEDTAVYYCAR SPNWDGAWFAHW GQGTLVTVS S(SEQ ID NO :85) Anti-LOX VK1 Light Chain Sequences

GACATTGTGCTGACCCAATCTCCAGACTCTTTGGCTGTGTCTCTAGGGGAGAGGG CCACCATCAACTGCAAGGCCAGCCAAAGTGTTGATTATGATGGTGATAGTTATAT GAACTGGTTCCAACAGAAACCAGGACAGCCACCCAAACTCCTCATCTATGCTGC ATCCAATCTAGAATCTGGCATCCCAGCCAGGTTTAGTGGCAGTGGGTCTGGGACA GACTTCACCCTCACCATCAACAGCCTGGAGGAGGAGGATGCTGCAACCTATTACT GTCAGCAAAGTAATGAGGACCCATTCACGTTCGGCCAGGGGACAAAGCTCGAGA TCAAA(SEQ ID NO :86)

DIVLTQSPDSLAVSLGERATINC KASQSVDYDGDSYMNW F Q QKPGQPPKLLIY AASNLESG IPARFSGSGSGTDFTLTINSLEE EDAATYYC QQSNEDPFTF GQGT LEI K(SEQ ID NO :87)

Anti-LOX VK2 Light Chain Sequences

GACATTGTGCTGACCCAATCTCCAGACTCTTTGGCTGTGTCTCTAGGGGAGAGGG CCACCATCAACTGCAAGGCCAGCCAAAGTGTTGATTATGATGGTGATAGTTATAT GAACTGGTTCCAACAGAAACCAGGACAGCCACCCAAACTCCTCATCTATGCTGC ATCCAATCTAGAATCTGGCATCCCAGCCAGGTTTAGTGGCAGTGGGTCTGGGACA GACTTCACCCTCACCATCAACAGCCTGGAGCCTGAGGATTTCGCAACCTATTACT GTCAGCAAAGTAATGAGGACCCATTCACGTTCGGCCAGGGGACAAAGCTCGAGA TCAAA(SEQ ID NO :88)

DIVLTQSPDSLAVSLGERATINC KASQSVDYDGDSYMNW F Q QKPGQPPKLLIY AASNLESG IPARFSGSGSGTDFTLTINSLEP EDFATYYC OQSNEDPFTF G Q G T K L E I K(SEQ ID NO :89)

Anti-LOX VK3 Light Chain Sequences

GACATTGTGATGACCCAATCTCCAGACTCTTTGGCTGTGTCTCTAGGGGAGAGGG CCACCATCAACTGCAAGGCCAGCCAAAGTGTTGATTATGATGGTGATAGTTATAT GAACTGGTTCCAACAGAAACCAGGACAGCCACCCAAACTCCTCATCTATGCTGC ATCCAATCTAGAATCTGGCATCCCAGCCAGGTTTAGTGGCAGTGGGTCTGGGACA GACTTCACCCTCACCATCAACAGCCTGGAGCCTGAGGATTTCGCAACCTATTACT GTCAGCAAAGTAATGAGGACCCATTCACGTTCGGCCAGGGGACAAAGCTCGAGA TCAAA(SEQ ID NO :90)

DIVMTQSPDSLAVSLGERATINC KASQSVDYDGDSYMNW F Q QKPGQPPKLLIY AASNLESG IPARFSGSGSGTDFTLTINSLEP EDFATYYC OQSNEDPFTF G Q G T K L E I K(SEQ ID NO :91)

For SEQ ID NOs 92- 122 CDR nucleotide and protein sequences are underlined.

Corresponding amino acid translation product is given below each nucleotide sequence. CDR definitions according to Kabat Anti-CD40 VH1 Heavy Chain Sequences

GAAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCCGGAGGGTCCCT

GAAACTCTCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTG GGTTCGCCAGGCCCCAGGCAAGGGCCTGGAGTGGGTCGCATACATTAATTCTG GTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCGATTCACCATCTCCA GAGACAATGCCAAGAACACCCTGTACCTGCAAATGAGCCGGCTGAGGGCCGAG GACACAGCCGTGTATTACTGTGCAAGACGGGGGTTACCGTTCCATGCTATGGAC TATTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCA(SEQ ID NO :92)

EVKLVESGGGLVOPGGSL LSCATSGFTFSDYY YWVROAPGKGLEWVAYINSGG GSTYYPDTVKGRFTISRDNAKNTLYLQMSRLRAEDTAVYYCARRGLPFHAMDYWG QGTSVTVSS (SEQ ID NO :93)

Anti-CD40 VH2 Heavy Chain Sequences

GAAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCCGGAGGGTCCCT GA A ACTCTCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTG GGTTCGCCAGGCCCCAGGCAAGGGCCTGGAGTGGGTCGCATACATTAATTCTG GTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCGATTCACCATCTCCA GAGACAATGCCAAGAACACCCTGTACCTGCAAATGAACAGCCTGAGGGCCGAG GACACAGCCGTGTATTACTGTGCAAGACGGGGGTTACCGTTCCATGCTATGGAC TATTGGGGTCAAGGAACCCTGGTCACCGTCTCCTCA(SEQ ID NO :94)

EVKLVESGGGLVOPGGSLKLSCATSGFTFSDYYMYWVRQAPGKGLEWVAYINSGG GSTYYPDTVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCARRGLPFHAMDYWG QGTLVTVSS (SEQ ID NO :95)

Anti-CD40 VH3 Heavy Chain Sequences

GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCCGGAGGGTCCCT GAAACTCTCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTG GGTTCGCCAGGCCCCAGGCAAGGGCCTGGAGTGGGTCGCATACATTAATTCTG GTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCGATTCACCATCTCCA GAGACAATGCCAAGAACACCCTGTACCTGCAAATGAACAGCCTGAGGGCCGAG GACACAGCCGTGTATTACTGTGCAAGACGGGGGTTACCGTTCCATGCTATGGAC TATTGGGGTCAAGGAACCCTGGTCACCGTCTCCTCA(SEQ ID NO :96) EVOLVESGGGLVOPGGSLKLSCATSGFTFSDYYMYWVRQAPGKGLEWVAYINSGG GSTYYPDTVKGRFTISRDNA NTLYLQMNSLRAEDTAVYYCARRGLPFHAMDYWG QGTLVTVSS (SEQ ID NO :97) Anti-CD40 VH4 Heavy Chain Sequences

GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCCGGAGGGTCCCT GAAACTCTCCTGTGCAGCCTCTGGATTCACTTTCAGTGACTATTACATGTATTG GGTTCGCCAGGCCCCAGGCAAGGGCCTGGAGTGGGTCGCATACATTAATTCTG GTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCGATTCACCATCTCCA GAGACAATGCCAAGAACACCCTGTACCTGCAAATGAACAGCCTGAGGGCCGAG GACACAGCCGTGTATTACTGTGCAAGACGGGGGTTACCGTTCCATGCTATGGAC TATTGGGGTCAAGGAACCCTGGTCACCGTCTCCTCAfSEQ ID NO :98) EVOLVESGGGLVOPGGSLKLSCAASGFTFSDYYMYWVROAPGKGLEWVAYINSGG GSTYYPDTV GRFTISRDNAKNTLYLQMNSLRAEDTAVYYCARRGLPFHAMDYWG QGTLVTVSS (SEQ ID NO :99)

Anti-CD40 VK1 Light Chain Sequences

GATATCCAGATGACACAGAGCACATCCTCCCTGTCTGCCTCTGTGGGAGACAG AGTCACCATCACCTGCAGTGCAAGTCAGGGCATTAGCAATTATTTAAACTGGTA TCAGCAGAAACCAGGCAAGGCCGTTAAACTCCTGATCTATTACACATCAATTTT ACACTCAGGAGTCCCATCAAGGTTCAGTGGCAGTGGGTCTGGGACAGATTATA CCCTCACCATCAGCTCCCTGCAGCCTGAAGATATTGCCACTTACTATTGTCAGC AGTTTAATAAGCTTCCTCCGACGTTCGGTGGAGGCACCAAACTCGAGGTGAAA( SEQ ID NO : 100)

DIOMTOSTSSLSASVGDRVTITCSASOGISNYLNWYOQ PGKAVKLLIYYTSILHSGV PSRFSGSGSGTDYTLTISSLOPEDIATYYCOOFNKLPPTFGGGTKLEVK (SEQ ID NO :101)

Anti-CD40 VK2 Light Chain Sequences

GATATCCAGATGACACAGAGCCCTTCCTCCCTGTCTGCCTCTGTGGGAGACAGA GTCACCATCACCTGCAGTGCAAGTCAGGGCATTAGCAATTATTTAAACTGGTAT CAGCAGAAACCAGGCAAGGCCGTTAAACTCCTGATCTATTACACATCAATTTTA CACTCAGGAGTCCCATCAAGGTTCAGTGGCAGTGGGTCTGGGACAGATTATAC CCTCACCATCAGCTCCCTGCAGCCTGAAGATTTCGCCACTTACTATTGTCAGCA GTTTAATAAGCTTCCTCCGACGTTCGGTGGAGGCACCAAACTCGAGGTGAAAfS EQ ID NO :102)

DIOMTOSPSSLSASVGDRVTITCSASOGISNYLNWYQQKPGKAVKLLIYYTSILHSGV PSRFSGSGSGTDYTLTISSLOPEDFATYYCQQFNKLPPTFGGGTKLEVK (SEQ ID NO :103)

Anti-CD40 VK3 Light Chain Sequences

GATATCCAGATGACACAGAGCCCTTCCTCCCTGTCTGCCTCTGTGGGAGACAGA GTCACCATCACCTGCAGTGCAAGTCAGGGCATTAGCAATTATTTAAACTGGTAT CAGCAGAAACCAGGCAAGGCCCCTAAACTCCTGATCTATTACACATCAATTTTA CACTCAGGAGTCCCATCAAGGTTCAGTGGCAGTGGGTCTGGGACAGATTATAC CCTCACCATCAGCTCCCTGCAGCCTGAAGATTTCGCCACTTACTATTGTCAGCA GTTTAATAAGCTTCCTCCGACGTTCGGTGGAGGCACCAAACTCGAGGTGAAA(S EQ ID NO :104)

DIQMTOSPSSLSASVGDRVTITCSASOGISNYLNWYOQKPGKAPKLLIYYTSILHSGVP SRFSGSGSGTDYTLTISSLQPEDFATYYCQQFNKLPPTFGGGTKLEVK (SEQ ID NO :105) Anti-DCIR VHlHeavy Chain Sequences

CAGGTTACTCTGAAAGAGTCTGGCCCTGCCATAGTGAAGCCCACCCAGACCCTC ACCCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGA GCTGGATTCGTCAGCCTTCAGGAAAGGCCCTGGAGTGGCTGGCACACATTTACT GGGATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCC AAGGATACCTCCAAGAACCAGGTTGTGCTCACCATGACCATTGTGGACACTGT GGATGCTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTA CGGGGGATACTTCGATGTCTGGGGCCAGGGGACCACGGTCACCGTCTCCTCA(S EQ ID NO :106) OVTLKESGPAIVKPTOTLTLTCSFSGFSLSTSGMGLSWIRQPSGKALEWLAHIYWDDD KRY PSLKSRLTISKDTSKNQVVLTMTIVDTVDAATYYCARSSHYYGYGYGGYFDV WGQGTTVTVSS (SEQ ID NO :107) Anti-DCI VH2 Heavy Chain Sequences

CAGGTTACTCTGAAAGAGTCTGGCCCTGCCATAGTGAAGCCCACCCAGACCCTC ACCCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGA GCTGGATTCGTCAGCCTTCAGGAAAGGCCCTGGAGTGGCTGGCACACATTTACT GGGATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCC AAGGATACCTCCAAGAACCAGGTTGTGCTCACCATGACCAACATGGACCCTGT GGATGCTGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTA CGGGGGATACTTCGATGTCTGGGGCCAGGGGACCACGGTCACCGTCTCCTCA(S EQ ID NO :108)

OVTLKESGPAIVKPTOTLTLTCSFSGFSLSTSGMGLSWIRQPSGKALEWLAHIYWDDD RY PSLKSRLTISKDTSKNQVVLTMTNMDPVDAATYYCARSSHYYGYGYGGYFD VWGQGTTVTVSS (SEQ ID NO :109) Anti-DCIR VH3 Heavy Chain Sequences

CAGGTTACTCTGAAAGAGTCTGGCCCTGCCCTGGTGAAGCCCACCCAGACCCTC ACCCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGA GCTGGATTCGTCAGCCTTCAGGAAAGGCCCTGGAGTGGCTGGCACACATTTACT GGGATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCC AAGGATACCTCCAAGAACCAGGTTGTGCTCACCATGACCAACATGGACCCTGT GGATACCGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTA CGGGGGATACTTCGATGTCTGGGGCCAGGGGACCACGGTCACCGTCTCCTCA

(SEQ ID NO : 110) OVTL ESGPALVKPTOTLTLTCSFSGFSLSTSGMGLSWIROPSGKALEWLAHIYWDD D RYNPSLKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCARSSHYYGYGYGGYFD VWGQGTTVTVSS (SEQ ID NO :111)

Anti-DCIR VH4 Heavy Chain Sequences

CAGGTTACTCTGAAAGAGTCTGGCCCTGCCCTGGTGAAGCCCACCCAGACCCTC ACCCTGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGA GCTGGATTCGTCAGCCTCCTGGAAAGGCCCTGGAGTGGCTGGCACACATTTACT GGGATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCC AAGGATACCTCCAAGAACCAGGTTGTGCTCACCATGACCAACATGGACCCTGT GGATACCGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTA CGGGGGATACTTCGATGTCTGGGGCCAGGGGACCACGGTCACCGTCTCCTCA(S EQ ID NO :112)

OVTLKESGPALV PTOTLTLTCSFSGFSLSTSGMGLSWIRQPPGKALEWLAHIYWDD DKRYNPSLKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCARSSHYYGYGYGGYFD VWGQGTTVTVSS (SEQ ID NO :113) Anti-DCIR VH5 Heavy Chain Sequences

CAGGTTACTCTGAAAGAGTCTGGCCCTGCCCTGGTGAAGCCCACCCAGACCCTC ACCCTGACTTGTACCTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGA GCTGGATTCGTCAGCCTCCTGGAAAGGCCCTGGAGTGGCTGGCACACATTTACT GGGATGATGACAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCC AAGGATACCTCCAAGAACCAGGTTGTGCTCACCATGACCAACATGGACCCTGT GGATACCGCCACATACTACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTA CGGGGGATACTTCGATGTCTGGGGCCAGGGGACCACGGTCACCGTCTCCTCA(S EQ ID NO :114) OVTLKESGPALV PTOTLTLTCTFSGFSLSTSGMGLSWIRQPPGKALEWLAHIYWDD DKRYNPSLKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCARSSHYYGYGYGGYFD VWGQGTTVTVSS (SEQ ID NO :115)

Anti-DCIR VK1 Light Chain Sequences

AACATTGTGCTGACCCAATCTCCAGACTCTTTGGCTGTGTCTCTAGGGGAGAGG GCCACCATAAACTGCAGAGCCAGTGAAAGTATTCATAGTTATGGCAATAGTTTT CTGCACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCTT GCATCCAACCTAGAATCTGGGGTCCCTAGCAGGTTCAGCGGCAGTGGGTCTAG GACAGACTTCACCCTCACCATTAGCAGCCTGCAGGCTGAGGATGCTGCAACCT ATTACTGTCAGCAAAATAATGAGGACCCGTGGACGTTCGGTCAGGGCACCAAG CTCGAGATCAAA(SEQ ID NO :116)

NIVLTOSPDSLAVSLGERATINCRASESIHSYGNSFLHWYQQKPGQPPKLLIYLASNLE SGVPSRFSGSGSRTDFTLTISSLOAEDAATYYCQONNEDPWTFGQGTKLEIK (SEQ ID NO :117)

Anti-DCIR VK2 Light Chain Sequences

AACATTGTGCTGACCCAATCTCCAGACTCTTTGGCTGTGTCTCTAGGGGAGAGG GCCACCATAAACTGCAGAGCCAGTGAAAGTATTCATAGTTATGGCAATAGTTTT CTGCACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCTT GCATCCAACCTAGAATCTGGGGTCCCTAGCAGGTTCAGCGGCAGTGGGTCTAG GACAGACTTCACCCTCACCATTAGCAGCCTGCAGCCTGAGGATTTCGCAACCTA TTACTGTCAGCAAAATAATGAGGACCCGTGGACGTTCGGTCAGGGCACCAAGC TCGAGATCAAA(SEQ ID NO :118)

NIVLTOSPDSLAVSLGERATINCRASESIHSYGNSFLHWYQOKPGOPPKLLIYLASNLE SGVPSRFSGSGSRTDFTLTISSLQPEDFATYYCQQN EDPWTFGQGTKLEIK (SEQ ID NO :119)

Anti-DCIR VK3 Light Chain Sequences

GACATTGTGCTGACCCAATCTCCAGACTCTTTGGCTGTGTCTCTAGGGGAGAGG GCCACCATAAACTGCAGAGCCAGTGAAAGTATTCATAGTTATGGCAATAGTTTT CTGCACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCTT GCATCCAACCTAGAATCTGGGGTCCCTAGCAGGTTCAGCGGCAGTGGGTCTAG GACAGACTTCACCCTCACCATTAGCAGCCTGCAGCCTGAGGATTTCGCAACCTA TTACTGTCAGCAAAATAATGAGGACCCGTGGACGTTCGGTCAGGGCACCAAGC TCGAGATCAAA (SEQ ID NO : 120)

DIVLTOSPDSLAVSLGERATINCRASESIHSYGNSFLHWYOOKPGOPPKLLIYLASNLE SGVPSRFSGSGSRTDFTLTISSLOPEDFATYYCQQNNEDPWTFGQGTKLEIK (SEQ ID NO :121)

Anti-DCIR VK4 Light Chain Sequences

GACATTGTGATGACCCAATCTCCAGACTCTTTGGCTGTGTCTCTAGGGGAGAGG GCCACCATAAACTGCAGAGCCAGTGAAAGTATTCATAGTTATGGCAATAGTTTT CTGCACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCTT GCATCCAACCTAGAATCTGGGGTCCCTAGCAGGTTCAGCGGCAGTGGGTCTAG GACAGACTTCACCCTCACCATTAGCAGCCTGCAGCCTGAGGATTTCGCAACCTA TTACTGTCAGCAAAATAATGAGGACCCGTGGACGTTCGGTCAGGGCACCAAGC TC G AG ATCA A A (SEQ ID NO : 122)

DIV TOSPDSLAVSLGERATI CRASESIHSYGNSFLHWYOOKPGOPP LLIYLASNL ESGVPSRFSGSGSRTDFTLTISSLQPEDFATYYCOON EDPWTFGQGTKLEIK (SEQ ID NO :123)

[manti-CD40_12E12.3F3_H-V-hIgG4H-C] Mouse monoclonal 12E12 heavy chain variable region (underlined) grafted onto human IgG4 H chain:

GENBANK ACCESSION # AEK24920.1

EVKLVESGGGLVQPGGSLKLSCATSGFTFSDYYMYWVROTPEKRLEWVAYINS GGGSTYYPDTVKGRFTISRDNAKNTLYLOMSRLKSEDTAMYYCARRGLPFHAM DYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDK RVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDP EVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKV SNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNY TTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEA LHNHYTQKSLSLSLGKAS (SEQ ID NO :124)

[manti-CD40_12E12.3F3_K-V-hIgGK-C] Mouse monoclonal 12E12 light chain variable region (underlined) grafted onto human gamma chain

GENBANK ACCESSION #AEK24921.1

DIOMTOTTSSLSASLGDRVTISCSASOGISNYLNWYQOKPDGTVKLLIYYTSILHS GVPSRFSGSGSGTDYSLTIGNLEPEDIATYYCOOFNKLPPTFGGGTKLEIKRTVA APSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO :125)

EXAMPLE 2: CHARACTERIZATION OF ANTIBODIES [00206] Humanized anti-LOX-1 15C4 antibodies were characterized. The relative IC50 and ED50 values were calculated by dividing the value for the test antibody by that of the chimeric anti-LOX-1 15C4 antibody. These data were generated using pure LOX-1 ectodomain proteins from human and Rhesus macaque and indicate that the humanized antibodies retain the anti-LOX-1 binding properties of the parental chimeric anti-LOX-1 15C4 mAb (Table 2).

TABLE 2

EXAMPLE 3: T CELL RESPONSE WITH CONSTRUCTS [00207] Vaccine dose in primates for the anti-LOX-1 -ENV was 250 ug at each time indicated. Results are ELISPOT for IFNg raised against HIV peptides by PMBCs as indicated. Adjuvants (administered at the same time as the vaccine) were PLA and poly ICLC, with only the latter yielding productive T cell responses focused to HIV ENV peptides. Results in FIGs. 2-4 show that the anti-LOX-1 -ENV vaccine with poly ICLC can boost specific T cell responses either in the setting of previously primed with NYVAC (group 1), or can prime when used alone (group 3).

EXAMPLE 4: RESPONSES ELICITED BY HIV-ENV VACCINES

[00208] The response of B cells, T cells and other immune cell types to HIV env vaccines can be tested by any of the methods described below. [00209] In vitro in PBMC and or DC/T cell co-cultures from HIV patients can be tested for the ability of LOX-l -ENV fusion proteins (or other ENV fusion proteins targeting different DC receptors) to expand antigen specific T cellsand/or B cells (only in PBMCs) using typical methods shown below. [00210] Culture amplified cytokine assay. To carry out a culture amplified cytokine assay, PBMCs (2 x 10⁶ cells/well) or DC-T cells (10⁵ DCs, 2 x 10⁶ T cells/well) would be cultured in cRPMI medium (RPMI 1640, Invitrogen) containing 10% human serum type AB (Gemini Bio-Products), 2 mM L-glutamine, 50 U penicillin, 50 g/ml streptomycin, 1 X essential amino acid solution (all from Sigma), 25 mM HEPES, 55 μΜ 2- mercaptoethanol (all from Gibco) with or without HIV ENV fusion proteins at 37 °C and 5% C02. On day 2 of culture, 100 IU/ml of exogenous IL-2 (Bayer Healthcare) would be added. On day 4, 6 and 8 of culture, half of the medium would be replaced with fresh medium containing 100 IU/ml IL-2. On day 10, cultures would be washed with PBS IX, split and rechallenged as per the standard intracellular cytokine staining assay or as per extracellular cytokine secretion assay.

[00211] Surface and intracellular staining. Briefly, cells would be incubated for 6 h at 37 °C in 5% C02 with individual or pools of peptides of interest at a final concentration of 10 μ Μ each, or stimulated with SEB (Sigma) at 1 μ g/ml or left unstimulated (negative control). The secretion inhibitors brefeldin A (Sigma), or/and GolgiStop™ (BD Biosciences), and in some experiments the degranulation marker CD 107a- FITC (BD Biosciences) would be added for the final 5 h of culture. After the 6 h incubation, cells would be washed once with PBS IX at 1 ,200 rpm for 5 min. Then surface staining for CD3-PercP, CD4-PECy7, CD8-PB (unless otherwise stated, staining reagents, instrumentation and software were from BD Biosciences) and live/dead fixable aqua dye (Invitrogen) would be performed for 20 min at 4 °C prior to a second wash with PBS IX. PBMCs would be permeabilized with FACSPerm for 10 min at RT then washed again (1 ,200 rpm, 5 min) before intracellular staining for IFNy-APC or PE, TNFa-FITC, granzyme B- APC (Caltag) and perforin-FITC (Biolegend) would be performed in Perm/Wash 1 X buffer for 30 min at 4 °C. Finally PBMCs would be fixed with 1% paraformaldehyde in PBS IX before analysis on a two-laser CANTO II flow cytometer and data analyzed with FACSDiva software. Spectral compensation would be performed for each experiment with each individual mAb used in the surface and intracellular cytokines staining using compensation particles. [00212] Extracellular cytokine secretion assay. Cells would be incubated for 48 h at 37 °C in 5% C02 with individual or pools of peptides at a final concentration of 10 /i M each. Then culture supernatants would be harvested, UV-inactivated and then the secreted IFNy would be measured in the culture supernatants using Luminex® multiplex bead-based technology and a Bio-Plex 200 instrument (BioRad).

EXAMPLE 5: ANTI-LOX- 1 ENV VACCINE RESPONSES IN PRIMATES

TABLE 3 oiox-l/ oLox-l/ oLox-l/

1 6 YVAC-KC NYVAC-KC NYVAC-KC

PolylCLC PolylCLC PolylCLC

oiox-l/ oiox-l/ olox-1/

2 6 YVAC-KC NYVAC-KC NYVAC-KC

GLA GLA GLA

olox-1/ oiox-l/ oiox-l/

4 Placebo Placebo NYVAC-KC

PolylCLC PolylCLC PolylCLC

oiox-l/ oiox-l/ oiox-l/

4 Placebo Placebo NYVAC-KC

GLA GLA GLA

Total 20

[00213] AUP518 study design. Study design for testing anti-LOX- 1 -HIV Env gpl40 vaccine in Rhesus macaques- variables are 1 ) adjuvant (poly ICLC (Hiltonol® vs. GLA); priming with NYVAC-KC viral vaccine carrying HIV Env gpl40 sequence exactly matching that in the anti-LOX-l-Env vaccine and GagPolNef sequences which are not carried by the anti-LOX-l-Env vaccine, vs. no priming.

[00214] NYVAC-KC: expressing ZM96gpl40, ZM96gagCN54polnef 108 pfu injected IM.

[00215] antiLox-1 bearing ZM96gpl40 injected ID in 5 sites and both adjuvants (poly ICLC or GLA) injected in a single site SC. Dose : 250 micrograms protein with 1 mg Poly ICLC or 20 micrograms GLA.

[00216] Group 1 NYVAC prime and anti-LOX- 1 -Env/poly ICLC boost - IFNg ELISPOT and serum Env-IgG (Fig. 6). T and B cell responses from Group 1 NHP. T cell data is IFNg ELISPOT from fresh PBMCs. T cells were probed with 6 peptide pools for Gag, Pol, and Nef and three peptide pools for Env. These data are summed averages (4 NHPs) for responses to Gag+Nef+Pol peptide pools (non-Env) and summed averages for responses to the three Env peptide pools. The Env-specific IgG serum titers were measured by ELISA using plate bound (anchored via CBD-Dockerin) Cohesin-ZM96 gpl40 deleted for its 20 C-terminal residues. Serum titers are derived from EC50 estimates of the titration curves expressed as logl O EC50 and are averaged for the 4 NHPs in the group. The non-Env T cell responses (light gray) emanate from the NYVAC-LC vaccine bearing GagPolNef sequences. The data show that a single injection of anti-LOX-l -Env vaccine with poly ICLC evokes a robust anti-Env antibody response (Fig. 6, lower panel) and preferemtially expands Env-specific T cells (Fig. 6, upper panel).

[00217] Group 2 NYVAC prime and antiLox-l -Env/GLA boost. (Fig. 7) T and B cell responses from Group 2 NHP. T cell data is IGNg ELISPOT from fresh PBMCs. T cells were probed with 6 peptide pools for Gag, Pol, and Nef and three peptide pools for Env. These data are summed averages (4 NHPs) for responses to Gag+Nef+Pol peptide pools (light gray, non-Env) and summed averages for responses to the three Env peptide pools. The Env-specific IgG serum titers were measured by ELISA using plate bound (anchored via CBD-Dockerin) Cohesin-ZM96 gpl40 deleted for its 20 C-terminal residues. Serum titers are derived from EC50 estimates of the titration curves expressed as logl O EC50 and are averaged for the 4 NHPs in the group. The non-Env T cell responses (light gray bars) emanate from the NYVAC-LC vaccine bearing GagPolNef sequences. The data show that a single injection of anti-LOX-l-Env vaccine with GLAevokes a robust anti-Env antibody response (Fig. 7, lower panel) and preferentially expands Env-specific T cells (Fig. 7, upper panel). [00218] Group 3 antiLox-1 -Env/polyICLC prime & NYVAC boost (Fig. 8). T and

B cell responses from Group 3 NHP. T cell data is IGNg ELISPOT from fresh PBMCs. T cells were probed with 6 peptide pools for Gag, Pol, and Nef and three peptide pools for Env. These data are summed averages (4 NHPs) for responses to Gag+Nef+Pol peptide pools (light gray non-Env) and summed averages for responses to the three Env peptide pools. The Env-specific IgG serum titers were measured by ELISA using plate bound (anchored via CBD-Dockerin) Cohesin-ZM96 gpl40 deleted for its 20 C-terminal residues. Serum titers are derived from EC50 estimates of the titration curves expressed as logl O EC50 and are averaged for the 4 NHPs in the group. The data show that ENV-specific T cells (Fig. 8, upper panel) and Env-specific antibodies (Fig. 8, lower panel) are evoked by the anti-LOX-l -Env vaccine, and are boosted by NYVAC- C virus challenge. However, Env-specific antibody responses require three vaccinations with vaccine plus adjuvant for a maximal response. [00219] Group 4 antiLox-l -Env/GLA prime & NYVAC boost. (Fig. 9) T and B cell responses from Group 4 NHP. T cell data is IGNg ELISPOT from fresh PBMCs. T cells were probed with 6 peptide pools for Gag, Pol, and Nef and three peptide pools for Env. These data are summed averages (4 NHPs) for responses to Gag+Nef+Pol peptide pools (light gray non-Env) and summed averages for responses to the three Env peptide pools. The Env-specific IgG serum titers were measured by ELISA using plate bound (anchored via CBD-Dockerin) Cohesin-ZM96 gpl40 deleted for its 20 C-terminal residues. Serum titers are derived from EC50 estimates of the titration curves expressed as log 10 EC50 and are averaged for the 4 NHPs in the group. The data show that Env-specific antibodies (Fig. 9, lower panel) are evoked by the anti-LOX-l -Env vaccine. However, Env-specific antibody responses require three vaccinations with vaccine plus adjuvant for a maximal response. Env- specific T cell responses with anti-LOX-1 + GLA are weak compared to those with poly ICLC adjuvant, but are boosted greatly with a NYVAC challenge.

[00220] AUP518 study summary IFNg ELISPOT and Env-IgG. (Fig. 10) T and B cell responses from Groups 1 -4 NHP. T cell data is IGNg ELISPOT from fresh PBMCs. T cells were probed with 6 peptide pools for Gag, Pol, and Nef and three peptide pools for Env. These data are summed averages (4 NHPs) for responses to Gag+Nef+Pol peptide pools (light gray non-Env) and summed averages for responses to the three Env peptide pools. The Env-specific IgG serum titers were measured by ELISA using plate bound (anchored via CBD-Dockerin) Cohesin-ZM96 gpl40 deleted for its 20 C-terminal residues. Serum titers are derived from EC50 estimates of the titration curves expressed as logl O EC50 and are averaged for the 4 NHPs in the group.

[00221] AUP518 total T cell responses by ICS (Fig. 1 1). Data showing that both CD4+ and CD8+ Env-specific T cells are evoked by the anti-LOX-l -Env vaccine at the time points sampled. Week 6 is 14 days post the second NYVAC injection and Week 22 is 14 days post the third aLOX-l-Env gpl40 vaccination. No ICS was performed for Groups 3 and 4 at week 6 (no treatment to that point). Data needs statistical analysis, but it appears that antiLOX-l -Env gpl40 vaccine may boost MVA-primed CD4+ and CD8+ T cell responses (Groups 1 and 2) and primes both CD4+ and CD8+ T cell responses (Groups 2 and 3). [00222] AUP518 CD4⁺ T cell epitope targets (Fig. 12). Data showing that (Fig. 12, left side) anti-LOX-l -Env vaccination shifts the antigen-specificity of the CD4+ T cells towards Env and that te response is broad as defined by the three Env peptide pool regions sampled. On the right hand side the HIV-specific CD4+ T cell response is mainly directed to Env and again the response is broad. T cell quality (not shown) as measured by procuction of multiple cytokines was high. NYVAC elicits CD4+ T cell responses dominated by GAG and POL but antiLOX-l -Env g l 40 greatly expands ENV-specific CD4+ T cell responses (Groups 1 and 2). As expected, antiLOX-l -ENV gpl40 vaccination without NYVAC priming expands Env-specific CD4+ T cell responses (Groups 3 and 4). Except for Group 4, CD4+ T cell quality (IFNy+, TNFa+, 1L-2+) is high.

[00223] AUP518 CD8⁺ T cell epitope targets (Fig. 13). Data showing that (Fig. 13, left side) anti-LOX-l -Env vaccination does not significantly the antigen-specificity of the CD8+ T cells towards Env. On the right hand side the HIV-specific CD8+ T cell response is mainly directed to a broad Env response - non-Env responses are background for the assay. T cell quality (not shown) as measured by procuction of multiple cytokines was low-moderate. Breadth of NYVAC-primed CD8+ T cell responses are not greatly altered by the antiLOX-l - ENV gpl 40 boost (Groups 1 and 2). Non-ENV CD8+ T cell responses from antiLOX-l -ENV gpl 0 vaccination without NYVAC priming (Groups 3 and 4) reflect non-specific background in this assay. In all Groups, CD8+ T cell quality (IFNy+, TNFa+, IL-2+) is low- moderate (1 -2 cytokines).

[00224] Summary of AUP518 antibody responses. 100% response rate to all gp l40 antigens at weeks 22 and 32. 100% response rate to V 1 V2 antigens at week 22 for groups 1-3. Response rates to V1V2 antigens were variable at week 32. At week 22, gpl40 response magnitude was higher for groups 1 -3 compared to group 4 (SCHARP analysis pending). Env gpl40 and V1V2 IgG response magnitude declined from week 22 to 32 for groups 1 and 2 (SCHARP analysis pending).

[00225] AUP518 anti-Env IgG magnitude in plasma (Fig. 14). Anti-Env serum antibody responses tested against a panel of different HIV virus Env proteins. Homologous Env corresponding to the vaccine sequence is the top left panel. Data indicate significant cross-reactivity to non-homologous Env sequences. Data for serum at weeks -3 (base-lineO and weeks 22 and 32 are presented.

[00226] AUP 518 IgG response rate - V1 V2 (Fig. 15). Survey of sera from the indicated time-points of reactivity of IgG to the V 1 V2 region of Env testing two Env sequences as shown. All except the anti-LOX-l/GLA group had a 100% response rate by this assay.

[00227] AUP518 neutralizing antibody responses. Summary of serum viral neutralization activity in the week 22 and week 32 samples. This analysis shows that the vaccines could evoke considerable neutrlaizing activity against Clade C viruses (the antiLOX-l-Env sequence was Clade C), but not against more distant Clade B viruses. TZM.bl assays against a panel of Tier 1 and Tier 2 HIV-1 Env pseudoviruses: NAb activity was detected against the more sensitive viruses, MW965.26 (clade C) and TH023.6 (AE). No neutralization was detected against the clade B Tier 1 viruses or Tier 2 isolates. A3R5 neutralization data: pre-immune, week 22 and week 32 samples were assayed against five Tier 2 clade C IMC.LucR viruses in A3R5.7 cells. The inventors detected weak neutralizing antibody activity in many animals against TV 1.21.LucR and Ce2010_F5.LucR, and weak sporadic neutralization of the other three viruses.

[00228] In the naive NHP groups, anti-Env IgG titers were elicited to maximal levels at 2 weeks after the third vaccination and were significantly more robust with poly ICLC (-log EC50 2.3E3) vs. GLA (-log EC50 6.4E2) adjuvant. Env-specific T cell responses were maximal (-400 spots per 10E6 cells) at 2 weeks after the second vaccination and were only observed in the group with poly ICLC adjuvant. In the virus-primed groups, anti-Env IgG titers were maximal (-log EC50 2.3-3.1E3) 2 weeks after the first aLOX-l .HIV Env gpl 40 vaccination and were similar with both adjuvants. However, Env-specific T cell responses were more robust (200-300 spots per 10E6 cells) in the poly ICLC group. Overall, the DC-targeting vaccines elicited both CD4⁺ and CD8⁺ T cell responses against multiple ENV epitopes, and especially for the CD4⁺ T cells, the quality was high. Neutralizing antibodies were specific to clade C viruses. EXAMPLE 6: CD40 DC TARGETING ENV VACCINES

[00229] DC targeting ENV vaccines - QA. Fig. 16 shows (left panel) an assay for receptor binding (to DCIR ectodomain) of three seperate preparations of a anti-DCIR-Env gp l40 fusion protein - they all have comparable binding to the parental non-fusion antibody. The right panel shows an SDS PAGE analysis of the protein A -affinity purified products of several batched of the anti-DCIR-Env gpl40 fusion protein. [00230] Expansion of Env-specific T cells in vitro (Fig. 17). PBMCs stimulated with HIV-gpl 40Z fusion proteins, 10, 1 and 0.1 nM (darker color, higher concentration) for 10 days. Restimulation with peptide clusters, 13 peptides per cluster (10 clusters), final concentration l uM/peptide. Supernatants harvest after 2 days. Luminex analysis for IFNg. Non-targeting control IgG4-gpl40 only one concentration tested 10 nM. These data show that anti-CD40-Env-gpl 40 fusion protein can expand Env-specific T cells of different epitope specificities from HIV patient PBMCs and that the anti-CD40 fusion protein is more efficacious than a non-DC-targeting control antibody-Env-gpl40 fusion protein.

[00231] Env-fusion test using a specific CD4⁺ T cell clone (Fig. 18). Test of Env- FP using clones. Clones were used after 7 days of pha stimulation. Ratio APC:T cell for this experiment is 1 : 1. Clone from patient A2, against gpl40 (96ZM). This data shows that anti- CD40-Env gpl40 protein is particularly efficacious for presenting epitope via autologous B cell line to a CD4+ T cell clone.

[00232] antiCD40 12E12 mAb activates human B cells (Fig. 19). 10 nM antibody for 24 hr in PBMC culture gated on live CD 19⁺. Total PBMCs stimulated with Abs (10 nM) for 24 hours. Surface staining for costimulatory molecule CD86 and HLA classl (ABC) aand HLA class II (DR). Analysis showed on lymphocytes CD 19+ alive. This data shows that the parental non-fusion anti-CD4012E12 mAb can activate human B cells as determined by up- regulation of cell surface markers. [00233] antiCD40-Env proteins up-regulate surface CD86 on human B cells (Fig.

20). Total PBMCs stimulated with Abs (l OnM) for 24 hours. Surface staining for co- stimulatory molecule CD86. Analysis showed, MFI (median fluoresce intensity) on lymphocytes CD 19+ alive. This data shows that the humanized anti-CD4012E12 mAb (CD40 H3K2) with or without fused Env-gpl40 retains the ability to activate human B cells as determined by up-regulation of cell surface marker CD86.

[00234] antiCD40-Env proteins induce proliferation of human B cells (Fig. 21 ). 1 nM (dark gray) and 0.1 nM (light gray) antibody for 6 days in PBMC culture with IL-4 and IL-21 gated on live CD 19⁺ CFSE dim. Total PBMCs stimulated with Abs (l OnM) for 24 hours. Surface staining for co-stimulatory molecule CD86. Analysis showed, MFI (median fluoresce intensity) on lymphocytes CD 19+ alive. This data shows that the humanized anti- CD4012E12 mAb (CD40 H3K2) with or without fused Env-gpl40 retains the ability to induce proliferation of human B cells.

[00235] Enhanced DC targeting Env vaccines. Combining disparate Env sequences [Clade C 96ZM, CN54; Clade B BX08, SF162]. Directly linking TLR-L agents to the DC targeting vaccines [Flagellin and Tri-acylated lipoprotein].

[00236] Enhanced DC targeting Env vaccines (Fig. 22). This figure shows design of potentially enhanced DC-targeting vaccines bearing HIV Env sequences at the H chain C- terminus with a Flagellin module for TLR5/inflammasome activation appended to the L chain C-terminus. The graph at the right shows a does range of an anti-LOX-1 mAb linked to Flagellin vs. a control mAb with the same linkage - assayed for stimulation of IL-6 production in a human PBMC culture.

[00237] Enhanced DC targeting Env vaccines (Fig. 23). This figure shows design of potentially enhanced DC-targeting vaccines bearing HIV Env sequences at the H chain C- terminus with TLR2L module for adjuvant activity appended to the L chain C-terminus - in this case via dockerin directly fused to the L chain bound b non-covalently to a triacyl lipidated cohesin fusion protein (shown as Pam3-cohesin). The graph at the right shows a dose range of such a Pam3-cohesin protein assayed for IL-6 production from a human PBMC culture. This activity can be linked and potentiated by binding to a DC-targeting mAb fused to dockerin. [00238] antiCD40-Env proteins activate human B cells (Fig. 24). 10 mM antibody for 24 hr in PBMC culture gated on CD19+ live. Total PBMCs stimulated with Abs (10 nM) for 24 hours. Surface staining for co-stimulatory molecule CD86. Analysis showed, MFI (median fluoresce intensity) on lymphocytes CD 19+ alive. This graph shows that the humanized anti-CD40 H3K2 fusion proteins bearing dockerin and/or flagellin on their L chains retain the ability to activate cells. This is not affected by addition of unlinked Pam3- cohesin (3rd bar) or with Pam3-cohesin bound to the dockerin fusion (5th bar).

Ί*

[00239] All of the methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

REFERENCES

The following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference.

U .S. Patent No. 3,817,837

U.S. Patent No. 3,850,752

U.S. Patent No. 3,939,350

U.S. Patent No. 3,996,345

U.S. Patent No. 4,275, 149

U.S. Patent No. 4,277,437

U.S. Patent No. 4,366,241

U.S. Patent No. 4,472,509

U.S. Patent No. 4,938,948

U.S. Patent No. 5,196,066

U.S. Patent No. 5,741 ,957

U.S. Patent No. 5,750, 172

U.S. Patent No. 5,756,687

U.S. Patent No. 5,827,690

U.S. Patent No. 6,091 ,001

U.S. Patent Publication No. 2005/0106660

U.S. Patent Publication No. 2006/0058510

U.S. Patent Publication No. 2006/0088908

U.S. Patent Publication No. 2010/0285564

U.S. Patent Application No. 61/332,465

PCT/US 1992/009965

WO 1994/13804

WO 2006/056464

WO 2008/103947

WO 2008/103953

WO 2008/1 18587

WO 2010/104747

WO 2010/104761

WO 2012/021834

Atherton, et al, Biol Reprod. 32(1):155-71 , 1985.

Ausubel, et al, PNAS USA. 93(26): 15317-22, 1996.

Banchereau, et al, Annu Rev Immunol. 18:767-81 1 , 2000.

Banchereau, et al, Cell 106(3):271 -4, 2001.

Barany & Merrifield, Anal Biochem. 95(1): 160-70, 1979.

Bird, et al, Science. 242(4877):423-6, 1988.

Burke, et al, J Virol. 68(5):2803-10, 1994.

Cella, et al, Curr Opin Immunol. 9(l): 10-6, 1997. Cumber, et al, J Immunol. 149(l): 12-6, 1992.

Dholakia, el al, J Biol Chem. 264(34):20638-42, 1989.

Glennie, et al, J Immunol. 139:2367-2375, 1987.

Goding, "Monoclonal antibodies," Academic Press: London, pp. 60-61 , 1986.

Holliger, et al, PNAS USA. 90:6444-6448, 1993.

Holliger & Winter, Cancer Metastasis Rev. 18:41 1 -419, 1999.

Holt, et al, Trends Biotechnol. 21(1 1 ):484-90, 2003.

Hu, et al, Cancer Res. 56(13):3055-61, 1996.

Huston, et al, Int Rev Immunol. 10(2-3): 195-217, 1988.

hatoon, et al, Prog Clin Biol Res. 317:801 -7, 1989.

King, et al, Biochemistry. 28(22):8833-9, 1989.

Kohl, et al, PNAS USA. 100(4): 1700-5, 2003.

Liu, et al, Cell Mol Biol. 49(2):209-16, 2003.

McCafferty, et al, Nature. 348(6301):552-4, 1990.

Mellman & Steinman, Cell 106(3):255-8, 2001.

Merchand, et al, Nature Biotech. 16:677-681 , 1998.

Merrifield, Science. 232(4748):341 -7, 1986.

O'Shannessy, et al, Biotechnol Appl Biochem. 9(6):488-96, 1987.

Owens & Haley, Biochem Biophys Res Commun. 142(3):964-71 , 1987.

Pack, et al, Biochemistry. 31 : 1579-84, 1992.

Panicali, et al, Proc. Natl. Acad. Sci. USA. 80: 53645368, 1983.

Potter & Haley, Methods Enzymol. 91 :614-33, 1983.

Reiter, et al, Nat Biotechnol. 14(l): 1239-45, 1996.

Repp, et al, J Hemat. 377-382, 1995.

Ridgeway et al, Protein Eng. 9:616-621 , 1996.

Skerra, J Mol Recognit. 13(4): 167-87, 2000.

Skerra, J Biotechnol. 74(4):257-75, 2001.

Staerz & Bevan, PNAS. 83(5): 1453-7, 1986.

Suresh, et al, Method Enzymol. 121 :210-228, 1986.

Steinman & Dhodapkar, J Exp Med. 193(2):233-8, 2001 .

Steinman, el al, Ann Rev Immunol. 9:271 , 1991.

Stewart & Young, "Solid Phase Peptide Synthesis," Freeman: SF, 1984.

Tarn, et al, Aust J Exp Biol Med Sci. 61(Pt 6):629-36, 1983.

Tigges, et al, J Immunol. 156(10):3901 -10, 1996.

Ward, et al, J Biol Chem. 264:8164-70, 1989.

Claims

WHAT IS CLAIMED IS:

1 . An HIV vaccine composition comprising a dendritic cell targeting complex comprising an anti-LOX-1 antibody, or a fragment thereof, attached to at least one HIV antigen.

2. The HIV vaccine composition of claim 1 , wherein the antibody and antigen are attached through a peptide linker (PL)

3. The HIV vaccine composition of claim 2, wherein the dendritic cell targeting complex comprises the following formula:

Ab-(PL-Ag)x;

Ab-(Ag-PL)x;

Ab-(PL-Ag-PL)x;

Ab-(Ag-PL-Ag)x;

Ab-(PL-Ag)x-PL; or

Ab-(Ag-PL)x-Ag;

wherein Ab is an anti-LOX-1 antibody or a fragment thereof; wherein PL is a peptide linker; wherein Ag is a HIV antigen; and wherein x is an integer from 1 to 20.

4. The HIV vaccine according to claim 2 or 3, wherein the PL comprises an alanine and a serine.

5. The HIV vaccine according to any one claim 2 to 4, wherein the PL further comprises a flexible linker.

6. The HIV vaccine according to any one claim 2 to 5, wherein the flexible linker comprises one or more glycosylation sites.

7. The HIV vaccine according to any one claim 2 to 6, wherein the flexible linker is QTPTNTI S VTPTNN STPTNN SNPKPNP (SEQ ID NO: 1 ).

8. The HIV vaccine according to claim 3, wherein the -(PL-Ag)x, -(Ag-PL)x, -(PL- Ag-PL)x, or -(Ag-PL-Ag)x are located at the carboxy terminus of the Ab heavy chain or fragment thereof.

9. The HIV vaccine according to claim 1 , wherein said anti-LOX-1 antibody or fragment is bound fused to one half of a Cohesin/Dockerin pair and said at least one HIV antigen is bound or fused to the complementary half of the Cohesin/Dockerin pair to form said antibody-antigen complex (Ab:Ag).

10. The HIV vaccine according to claim 9, wherein said antibody-antigen complex (Ab:Ag) comprises the following formula: Ab.Doc:Coh.Ag;

Ab.Coh:Doc.Ag;

Ab.(Coh)x:(Doc.Ag)x;

Ab.(Doc)x:(Coh.Ag)x;

Ab.(Coh.Doc)x:(Doc.Ag')(Coh.Ag²); or

Ab.(Coh)x(Doc)x:(Doc.Ag')x(Coh.Ag²)x;

wherein Ab is an anti-LOX-1 antibody or a fragment thereof; wherein Ag is a HIV antigen (Ag and Ag being two distinct HIV antigens); wherein Doc is Dockerin; wherein Coh is Cohesin and wherein x is an integer from 1 to 10.

11. The HIV vaccine according to any one claims 1 to 10, wherein said at least one HIV antigen elicits at least one of a humoral or a cellular immune response in a host.

12. The HIV vaccine according to claim 1 1 , wherein said at least one HIV antigen is select from the group consisting of HIV Gag, Pol, Pro, Tat, Nef, Rev, Vif, Vpr or Env antigens.

13. The HIV vaccine according to claim 12, wherein the Env antigen is selected form the group consisting of gp41 , gpl20, gpl40 and gpl40 with a C-terminal deletion.

14. The HIV vaccine according to any one claim 13, further comprising an adjuvant.

15. The HIV vaccine according to claim 14, wherein the adjuvant is conjugated to said anti-LOX-1 antibody or fragment thereof and/or to said at least one HIV antigen.

16. The HIV vaccine of claim 15, wherein the adjuvant is Poly ICLC, Immunoquid, CPG, GLA or TLR agonists.

17. A HIV vaccine comprising a population of dendritic cells (DC) activated with an antibody-antigen fusion protein (Ab.Ag) or an antibody-antigen complex (Ab:Ag) as described in any one claims 1 to 16.

18. A combined HIV vaccine comprising a first HIV vaccine according to any one claims 1 to 17 and a second HIV vaccine.

19. The combined HIV vaccine according to claim 17, wherein the second HIV vaccine is selected from the group consisting of an attenuated recombinant virus, a naked DNA vaccine and a DC-targeting vaccine.

20. The combined HIV vaccine according to claim 1 8, wherein the attenuated recombinant virus is an attenuated recombinant poxvirus.

21. The combined HIV vaccine according to claim 19, wherein the attenuated recombinant poxvirus is selected from the group consisting of N YVAC, ALVAC and MVA virus.

22. The combined HIV vaccine according to claim 20, wherein the NYVAC virus is a NYVAC-KC virus.

23. The combined HIV vaccine according to claim 18, wherein the DC-targeting vaccine is a vaccine comprising an anti-DC receptor antibody or a fragment thereof to which at least one HIV antigen is fused or conjugated to form an antibody-antigen fusion protein (Ab.Ag) or an antibody-antigen complex (Ab:Ag).

24. A method for preventing or treating an HIV infection comprising administering to a patient an HIV vaccine according to any one claims 1 to 17 or a combination of vaccines according to any one claims 18 to 23.

25. A method for inducing an immune response to at least one HIV epitope comprising administering to a patient an HIV vaccine according to any one claims 1 to 17 or a combination of vaccines according to any one claims 18 to 23.

26. A method for potentiating an immune response to at least one HIV epitope comprising administering to a patient an HIV vaccine according to any one claims 1 to 17 or a combination of vaccines according to any one claims 18 to 23.

27. A method of treating a patient in the early stages of an HIV infection comprising administering comprising administering to a patient an HIV vaccine according to any one claims 1 to 17 or a combination of vaccines according to any one claims 18 to 23.

28. The method of claim 27, wherein the antibody-antigen fusion protein (Ab.Ag) comprises a peptide linker (PL) between said anti-LOX-1 antibody or fragment thereof and said at least one HIV antigen.

29. The method of claim 28, wherein said antibody-antigen fusion protein (Ab.Ag) comprises the following formula:

Ab-(PL-Ag)x;

Ab-(Ag-PL)x;

Ab-(PL-Ag-PL)x;

Ab-(Ag-PL-Ag)x;

Ab-(PL-Ag)x-PL; or

Ab-(Ag-PL)x-Ag;

wherein Ab is an anti-LOX-1 antibody or a fragment thereof; wherein PL is a peptide linker; wherein Ag is a HIV antigen; and wherein x is an integer from 1 to 20.

30. The method of claim 28 or 29, wherein the PL comprises an alanine and a serine.

31. The method of any one claim 28 to 30, wherein the PL further comprises a flexible linker.

32. The method of claim 28 to 31 , wherein the flexible linker comprises one or more glycosylation sites.

33. The method of claim 28 to 32, wherein the flexible linker is QTPTNTISVTPTNNSTPTNNSNPKPNP (SEQ ID NO: 1).

34. The method of claim 29, wherein the -(PL-Ag)x, -(Ag-PL)x, -(PL-Ag-PL)x, or - (Ag-PL-Ag)x are located at the carboxy terminus of the Ab heavy chain or fragment thereof.

35. The method of claim 27, wherein the anti-LOX-1 antibody or fragment is bound fused to one half of a Cohesin/Dockerin pair and said at least one HIV antigen is bound or fused to the complementary half of the Cohesin/Dockerin pair to form said antibody-antigen complex (Ab:Ag).

36. The method of claim 35, wherein said antibody-antigen complex (Ab:Ag) comprises the following formula:

Ab.Doc:Coh.Ag;

Ab.Coh:Doc.Ag;

Ab.(Coh)x:(Doc.Ag)x;

Ab.(Doc)x:(Coh.Ag)x;

Ab.(Coh.Doc)x:(Doc.Ag¹)(Coh.Ag²); or

Ab.(Coh)x(Doc)x:(Doc.Ag')x(Coh.Ag²)x;

wherein Ab is an anti-LOX-1 antibody or a fragment thereof; wherein Ag is a HIV antigen (Ag¹ and Ag² being two distinct HIV antigens); wherein Doc is Dockerin; wherein Coh is Cohesin and wherein x is an integer from 1 to 10.

37. The method of any of claims 27 to 36, wherein the at least one HIV antigen elicits a humoral or cellular immune response in a host.

38. The method of claim 37, wherein said at least one HIV antigen is selected from the group consisting of HIV Gag, Pol, Pro, Tat, Nef, Rev, Vif, Vpr or Env antigens.

39. The method of claim 38, wherein the Env antigen is gp41 , gpl 20, gpl40 or gpl40 with a C-terminal deletion.

40. The method of any of claims 28 to 39, further comprising an adjuvant.

41. The method of claim 40, wherein the adjuvant is conjugated to said anti-LOX-1 antibody or fragment thereof and/or to said at least one HIV antigen.

42. The method of any one of claims 27 to 41 comprising a population of dendritic cells (DC) activated with an antibody-antigen fusion protein (Ab.Ag) or an antibody-antigen complex (Ab:Ag).

43. A method of treating a patient comprising administering a first HIV vaccine according to any one of claims 27 to 42 and administering a second HIV vaccine.

44. The method of claim 42, wherein the second HIV vaccine is selected from the group consisting of an attenuated recombinant virus, a naked DNA vaccine and a DC- targeting vaccine.

45. The method of claim 43, wherein the attenuated recombinant virus is an attenuated recombinant poxvirus.

46. The method of claim 44, wherein the attenuated recombinant poxvirus is selected from the group consisting of NYVAC, ALVAC and MVA virus.

47. The method of claim 45, wherein the NYVAC virus is a NYVAC -KC virus.

48. The method of claim 43, wherein the DC-targeting vaccine is a vaccine comprising an anti-DC receptor antibody, or a fragment thereof, to which at least one HIV antigen is fused or conjugated to form an antibody-antigen fusion protein (Ab.Ag) or an antibody-antigen complex (Ab:Ag).