MXPA06014880A - Adjuvancy and immune potentiating properties of natural products of onchocerca volvulus - Google Patents

Abstract

The present invention relates to a method for potentiating a specific immune response to an antigen in a mammal in need thereof. The method comprises administering to the mammal an effective amount ofOv-ASP, or at least one subunit ofOv-ASP, and an antigenic moiety.

Description

ADJUVANT AND IMMUNE POTENTIATING PROPERTIES OF NATURAL PRODUCTS OF ONCHOCERCA VOLVULUS BACKGROUND OF THE INVENTION The increased threat of a bio-terrorist attack in recent years underscores the critical need for the development of potent vaccine formulations to protect the susceptible population. Vaccine formulations contain antigens that induce immunity against pathogens. However, immune responses to many antigens, although detectable, are often of insufficient magnitude to provide protection against a disease process mediated by the agents expressing these antigens. In such situations, it is necessary to include an adjuvant together with the antigen in the vaccine formulation. An adjuvant is a compound that, when used in combination with specific vaccine antigens, potentiates the resulting immune response. The mechanism of action of adjuvants is not known precisely, and may not be the same for all adjuvants. However, it is believed that adjuvants prolong the bioavailability of an antigen. The adjuvants also seem to increase the size of the antigen, thus increasing the possibility of phagocytosis. Additionally, most of the adjuvants have a branch-stimulating effect mediated by cells of the immune system, i.e. on T lymphocytes (T cells). There are two well-defined sub-populations of T cells: cytotoxic T cells (Te) and adjuvant T cells (Th). Cytotoxic T cells kill intracellular pathogens. On the other hand, Th cells exert most of their functions by secreted cytokines. The adjuvant T cells are further divided into Thl and Th2 cell types. Differences in cytokine secretion patterns of Th cell types determine the type of immune response performed to challenge a particular antigen. In general, Thl cells stimulate cytotoxic responses against intra-cellular viruses, bacteria and protozoa via interferon-gamma secretion (IFN-α) and other pro-inflammatory cytokines. Cytotoxic responses include the activation of the Te cells. In contrast, Th2 cells are induced by allergens and helminth parasites, and are characterized by the secretion of interleukins, e.g., IL-4, IL-5, etc. Both types of Th cells stimulate the humoral branch of the immune system, ie the B lymphocytes. Different pathogens stimulate different types of immune responses mediated by cells. For example, infecting mice with a helminth parasite polarizes the immune response to Th2 activation. In some cases, the polarization is so potent that a Thl-dominant response to an infectious pathogen can be inhibited by the introduction of a helminth parasite (Brady et al., "Fasciola hepatic suppresses a protecti-ve Thi response against Bordetella pertussis" Infect. Immun.67: 5372-5378 (1999)). Similarly, a Thl-mediated autoimmune disease in mice can be removed by introducing a helminth parasite in mice (Cooke and collaborators "Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice" Parasite Immunol 21: 169 -176 (1999)). Additionally, the anti-inflammatory properties of the products of two helminth parasites have been shown to be able to down-modulate the inflammatory Thl responses in mice. In particular, the body fluid of the roundworm parasite of swine, Ascaris suum, potently stimulates the characteristic cytokines of Th2 cells (Paterson et al., "Modulation of a Heterologous Immune Response by the Products of Ascaris suum" Immunol., 70: 6058-67 (2002)). Likewise, it has been found that a secreted glycoprotein product, ES-62, of a rodent parasite, has broad anti-inflammatory properties that inhibit the production of Thl cytokines in experimentally induced arthritis in mice (Mclnnes et al., "A Novel Therapeutic Approach Targeting Articular Inflammation Using the Filarial Nematode-Derived Phosphorylcholine-Containing Glycoprotein ES-62" J. Immunol. 171: 2127-33 (2003)). This product is currently being developed as a novel anti-inflammatory therapeutic agent. Recently, two helminth products have been reported for their action as adjuvants. Both are strong inducers of Th2 responses to control proteins in a vaccine.

In particular, proteins secreted by adult Nippostrongylus brisiliensis (a parasite of rodents) were found to be strong inducers of Th2 responses in mice immunized with an unrelated protein (Holland et al., "Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as adjuvants for Th2 responses "Eur. J. Immuno1 .30 (7): 1977-1987 (2000)). Similarly, lacto-N-fucopen-taosa III, a carbohydrate found on the surface of the eggs of a human parasite, Schistosoma mansoni, acts as a Th2 adjuvant for a control protein when injected into mice (Okano et al. "Lacto-N- fucopentase III Found on Schistosoma mansoni Egg Antigens Functions as Adjuvant for Proteins by Inducing Th2-Type Response" J \ Immunol. 167: 442-450 (2001)). Until the present invention, it has been found that helminth products are Th2 dominantly potent. Consequently, its use as adjuvants has been to induce Th2 cell type responses. Although the activation of Th2 type cells is important, the activation of Thl cells is critical for the efficacy of certain vaccines. In addition to providing a different cytokine profile than that provided by Th2 cells, Thl cells activate cytotoxic effector mechanisms that do not activate Th2 cells. Moreover, other adjuvants currently used in human vaccines are also not effective in stimulating cytotoxic responses to intracellular pathogens. These adjuvants include aluminum salts, e.g., potassium aluminum sulfate, aluminum phosphate and aluminum hydroxide. Without the ability to stimulate cytotoxic responses to intracellular pathogens, the use of such adjuvants is limited. In addition to protecting against infectious diseases, vaccination is becoming significant in other developing technologies. These technologies include, for example, vaccination against syngeneic tumors. In such new approaches, it is important to be able to induce different types of immune responses. Consequently, there is a critical need for safe and effective adjuvants and therapeutic agents capable of amplifying immune responses to a wide variety of pathogens and against tumors. There is a particular need for adjuvants that amplify Thl cell responses. SUMMARY OF THE INVENTION In one embodiment, the present invention relates to a vaccine composition or immunogenic composition comprising an antigenic fraction; and an adjuvant comprising an effective amount of Ov-ASP, or at least one subunit of Ov-ASP. Ov-ASP includes Ov-ASP-1, Ov-ASP-2, and Ov-ASP-3. In another embodiment, the present invention relates to a method for enhancing a specific immune response to an antigen in a mammal that he needs it. The method comprises administering to the mammal an effective amount of Ov-ASP, or at least one subunit of Ov-ASP; and an antigenic fraction. In a further embodiment, the present invention relates to a method for stimulating a cellular response with secretion of cytokines in a mammal in need thereof. The method comprises administering to the mammal an effective amount of Ov-ASP, or at least one subunit of these proteins, where the secretion of cytokines is stimulated. In a further embodiment, the present invention relates to a method of generating an immune response or vaccinating a mammal in need thereof against onchocerciasis. The method comprises administering to the mammal an effective amount of Ov-ASP, or antigenic fragments of Ov-ASP, and a pharmaceutically acceptable carrier. In another aspect, the present invention relates to a method for preventing SARS (severe acute respiratory syndrome) in a mammal in need thereof. The method comprises administering to the mammal a vaccine composition comprising a SARS-CoV polyamino acid, and an effective amount of Ov-ASP, or at least one Ov-ASP sub-unit. In another aspect, the present invention relates to a method of preventing HIV infection in a mammal in need thereof. The method comprises administering to the mammal a vaccine composition comprising an HIV-1 polyamino acid, and an effective amount of Ov-ASP, or at least one subunit of Ov-ASP. Brief Description of the Drawings Figure 1. Cytokine secretion induced by rOv-ASP-1 (5 μ9 / p? 1) from PBMC obtained from individuals (n = 14) never exposed to Onchocerca volvulus. The cells were incubated with rOv-ASP-1 (+) or culture medium alone (-). * = P <0.05 versus cells in culture medium alone. The values are the mean + standard deviation (SD). Figure 2. Inhibition of LPS activity using polymyxin B (5 and 20 pg / ml) in human PBMC (three donors). ROv-ASP-1 was pre-incubated with polymyxin B for one hour at room temperature before adding PBMC. The values are the mean + DE. Figure 3. Cytokines produced by spleen cells from mice immunized with PBS or rOv-ASP-1 without adjuvants and stimulated in vitro with 5 pg / ml of rOv-ASP-1. The values are obtained from spleen cells gathered within each treatment group and represent the mean of cultures in triplicate. Figure 4. Mean IgGl and IgG2a anti-OVA titers in mice (n = 5 / group) immunized with control treatments (PBS, OVA, alum, MPL + TDM, rOv-ASP-1) or OVA combined with alum or MPL + TDM or the test adjuvant, rOv-ASP-1. The amounts of antibodies are expressed as optical density (OD) in the ELISA assay. Figure 5. Titers of IgGl and anti-OVA IgG2a in mice (n = 5 / group) bled pre-immunization (Pre) or after immunization with control treatments (PBS, OVA) or OVA combined with the test adjuvant , rOv-ASP-1 (25 yg / mouse), either treated (LPS-) or untreated (LPS +) with gel remover LPS The same symbols apply in both graphs. The anti-OVA IgGl titer of the endpoint was 512,000 and the anti-OVA IgG2a titer of the endpoint was 128,000. Figure 6. Cytokines produced by spleen cells from mice immunized with OVA with or without adjuvants or relevant control treatments and re-stimulated in vitro with 5 g / ml OVA. The values are obtained from spleen cells gathered within each treatment group and represent the mean of cultures in triplicate. Figure 7. Average amounts of total anti-SC-1 IgG in mouse sera (n = 5 / group) after immunization with control treatments (antigens or adjuvants alone) or antigens formulated with MPL + TDM or adjuvant rOv-ASP -1 of test. The amounts of anti-bodies are expressed as optical densities in the ELISA assays. Reciprocal dilutions of serum are indicated on the x-axis. The endpoints T are denoted; 250,000 in the presence of rOv-ASP-1 test, and 64,000 in the presence of MPL + TDM. Figure 8. Average amounts of total anti-FLSC IgG in mouse sera (n = 5 / group) after immunization with control treatments (antigens or adjuvants alone) or antigens formulated with MPL + TDM or adjuvant rOv-ASP-1 test. The amounts of anti-bodies are expressed as optical densities in the ELISA assays. Reciprocal dilutions of serum are indicated on the x-axis. The endpoints T are denoted; 1,024,000 in the presence of test rOv-ASP-1, and 1,024,000 in the presence of MPL + TDM. Detailed Description of the Invention The present invention comprises pharmaceutical compositions and methods for stimulating, ie, inducing and / or enhancing, immune responses in mammals. The invention includes the unexpected discovery that the proteins of a helminth parasite, Onchocerca volisulus, can stimulate various aspects of the immune response of mammals. The proteins used in the pharmaceutical compositions and methods of the invention are members of the Ov-ASP family (secreted protein associated with the activation of Onchocerca volvulus). Native Ov-ASP proteins are located in the secretory granules of the glandular esophagus and the surface of the infective third stage larvae of the Onchocerca volvulus helminth. Members of the Ov-ASP family include: Ov-ASP-1, Ov-ASP-2 and Ov-ASP-3. The sequence of Ov-ASP-1 is shown in SEQ ID NO: l. The sequence of Ov-ASP-2 is shown in SEQ ID NO: 2. The sequence of Ov-ASP-3 is shown in SEQ ID NO: 3. The Ov-ASP used in the compositions and methods of the invention it does not need to be 100% identical to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, as long as the protein retains the immunostimulatory properties of SEQ ID NO: 1, SEQ ID NO: 2 , or SEQ ID NO: 3. For example, Ov-ASP, for the purposes of this description, is approximately 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to the SEQ. ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. One or more subunits (ie, fragments) of Ov-ASP can be used in the compositions and methods of this invention. A subunit can be any length that produces the desired stimulation of an immune response (i.e., an active subunit). The minimum number of amino acids in a subunit includes, for example, at least about 20, 30, 40, 50, 60, 70, 80 and 90 amino acids. The maximum number of amino acids in a subunit includes, for example, at most around 253, 250, 240, 230, 220, 210, 200, 190, 180, 170, 160, 150, 140, 130, 120, 110 , and 100 amino acids. An adequate range of amino acids includes any number of the minimum and any number of the maximum. For the purposes of this description, "Ov-ASP" includes a full-length Ov-ASP-1, or one or more sub-units of a full-length Ov-ASP-1; a full-length Ov-ASP-2, or one or more sub-units of a full-length Ov-ASP-2; or a full-length Ov-ASP-3, or one or more sub-units of a full-length Ov-ASP-3. Ov-ASP proteins, and subunits of these proteins, can be prepared by methods known in the art. Preferably, the proteins are produced recombinantly. For example, the rOv-ASP-1 recombinant protein was expressed in E. coli using cDNA encoding Ov-ASP-1 (Ov-ASP-1; GenBank, access number AF020586). This recombinant protein has a molecular weight of 24,871 Daltons. The rOv-ASP-2 recombinant protein was expressed in E. coli using cDNA encoding Ov-ASP-2 (Ov-ASP-2; GenBank accession number H39490). This recombinant protein has a molecular weight of 29,047 Daltons. The rOv-ASP-3 recombinant protein was expressed in E. coli using cDNA encoding Ov-ASP-3 (Ov-ASP-3; GenBank, accession number AA917267). This recombinant protein has a molecular weight of 24,744 Daltons. See Tawe et al., "Angiogenic activity of Onchocerca volvulus recombinant proteins similar to vespid venom antigen 5" Mol. Biochem. Parasitol. 109: 91-99 (2000). The sequences and methods of providing Ov-ASP from US Pat. No. 6,723,322 (Lustigman et al.) Are incorporated herein by reference. Ov-ASP proteins can also be obtained by isolating the protein directly from Onchocerca volvulus by standard methods. Some suitable methods include chromatographic protocols by precipitation and liquids, such as ion exchange, hydrophobic interaction and gel filtration. (Methods Enzymol 182 (Guide to Protein Chemistry, Deutscher, editor, section VII) 309 (1990) and Scopes, Protein Purification, Springer-Verlag, NY (1987) Ov-ASP proteins can also be obtained by separating the protein in Preparative SDS-PAGE gels, slicing the band of interest and electro-levigating the polyacrylamide matrix protein Ov-ASP proteins can also be obtained by synthesizing the protein from individual amino acid residues, as is known in the art. (Stuart and Young "Solid Phase Peptide Synthesis", second edition, Pierce Chemical Co. (1984).) Administration of Ov-ASP proteins in the methods of the invention can be effected by administering the same protein, or by introducing an acid molecule nucleic acid encoding the protein in a manner that allows the expression of the protein.Preferably, the nucleic acid molecule is in the form of a recombinant expression vector, such as, for example, example, a purified plasmid. After administration of the expression vector to a mammalian cell, Ov-ASP is expressed intra-cellularly. The recombinant vectors may also contain a nucleotide sequence encoding suitable regulatory elements so as to effect the expression of the vector construct in a suitable host cell. Those skilled in the art will appreciate that a variety of enhancers and promoters are suitable for use in the constructions of the invention, and that the constructs will contain the initiation, termination and control sequences necessary for proper transcription and processing of the sequence of nucleic acid encoding an Ov-ASP when the recombinant vector construct is introduced into a subject. Vaccine Compositions or Immunogenic Compositions Comprising Ov-ASP as an Adjuvant In one embodiment, the invention relates to vaccine compositions or immunogenic compositions comprising Ov-ASP and an antigenic fraction. Ov-ASP is used as an adjuvant in these compositions. As an adjuvant, Ov-ASP potentiates an immune response to antigens that are not related to Ov-ASP. In this embodiment, vaccine compositions or immunogenic compositions comprising at least one antigenic fraction and an effective amount of Ov-ASP are provided. The vaccines of the invention may be prophylactic vaccines or therapeutic vaccines. A prophylactic vaccine prevents a disease from occurring by preparing the immune system to respond to an antigen. A therapeutic vaccine is given after an infection to reduce or stop the progression of the disease by producing or reinforcing an immune response. The ratio by weight of the antigenic fraction to Ov-ASP in the vaccine compositions or immunogenic compositions can be any ratio that allows to enhance a specific immune response. The amount of Ov-ASP to be added to a particular antigenic fraction depends on several factors, which would be known by a technician in the field. Factors include, for example, the age and weight of the mammalian subject, the mode of administration of the composition, the inherent immunogenicity of the particular antigen, the desired form of the response (elevation of titer, prolongation of the response, or both) , the presence of carriers, and other considerations that will be evident to the technicians in the matter. The quantity can be determined by means of routine experimentation. For example, the weight ratio of an antigenic fraction to Ov-ASP can vary from about 4: 1 to about 1: 1, or from about 4: 1 to about 1: 4. The antigenic fraction of the present invention may be an antigen or a nucleic acid molecule encoding an antigen. An antigen is a substance in which a specific immune response can be induced in a mammal. That is, an antigen is immunogenic. A specific immune response includes a humoral and / or cell-mediated immune response directed specifically against the antigen. For purposes of this description, an antigen includes substances that are capable of stimulating immune responses when administered to a mammal by themselves, and substances that are capable of stimulating immune responses only when administered to a mammal in conjunction with Ov- ASP. For example, the antigens can be polyamino immunogenic acids. Polyamino acids include oligopeptides, polypeptides, peptides, proteins and glycoproteins. The polyamino acid can be a naturally occurring isolated product, a synthetic product, or a polyamino acid product of genetic engineering. The length of a polyamino acid is not critical as long as the polyamino acid is immunogenic when administered in conjunction with Ov-ASP. Thus, the polyamino acid contains a sufficient number of amino acid residues to define at least one epitope of an antigen. Methods for isolating and identifying immunogenic fragments from known immunogenic proteins are described by Salfeld et al in J. Virol. 63: 798-808 (1989) and by Isola et al. In J. Virol. 63: 2325-2334 (1989). If a polyamino acid defines an epitope, but is too short to be immunogenic, it can be conjugated to a carrier molecule. Some carrier molecules include keyhole limpet hemocyanin, Ig sequences, TrpE, and human or bovine serum albumin. The conjugation can be carried out by methods known in the art. One such method is to combine a cysteine residue of the fragment with a cysteine residue in the carrier molecule. The antigens can also be a lipid, a lipopolysaccharide (glycolipid) or a polysaccharide. The length of these compounds is not critical as long as the compound induces an immune response. These compounds may also be chemically linked to protein carrier molecules in order to enhance immunogenicity. For example, a polysaccharide antigen, such as a bacterial capsular polysaccharide or fragment thereof, can be linked to a protein carrier molecule to form a glyco-conjugate. Methods for preparing bacterial capsular polysaccharide conjugates and protein carrier molecules are well known in the art, and can be found, for example, in Dick and Burret, Contrib icrobiol Immunol. 10: 48-114 (Cruse J M, Lewis R E Jr., editors; Basel Kruger (1989)). The antigens can be derived from various sources. The antigens are commercially available or can be produced as known to those skilled in the art. For example, antigens may be produced or derived from pathogenic microorganisms. Examples of microorganisms include viruses, e.g., polyoma virus; bacteria; mycoplasma; mushrooms; protozoa and other infectious agents. An antigen can be a complete microorganism. For example, an antigen can be a modified-living (ie, attenuated) microorganism or a dead microorganism. An antigen can also be an immunogenic component of a microorganism, or a product of a microorganism. For example, the antigen can be all or part of a protein, glycoprotein, glycolipid, polysaccharide or lipopolysaccharide that is associated with the microorganism. Pathogenic microorganisms from which antigens can be produced or derived for vaccine purposes are well known in the field of infectious diseases. Suitable pathogenic microorganisms are listed, for example, in Medical Microbiology, second edition (1990), J.C. Sherris (publisher), Elsevier Publishing Co. , Inc., New York, and Zinsser Microbiology, 20a. edition (1992), W.K. Joklik et al. (editors), Appleton & Lange Publishing Division, Prentice Hall, Englewood Cliffs, N.J., United States. Examples of microorganisms of particular interest for human vaccines include the human immunodeficiency virus (HIV), crown viruses that cause severe acute respiratory syndrome (SARS), Chlamydia, Haemophilus influenzae, Helicobacter pylori, Moraxella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Salmonella typhi, Streptococcus pneumoniae, herpes simplex virus, rhabdovirus, human papillomavirus , influenza, measles, respiratory syncytial virus, rotavirus, Norwalk virus, hepatitis A virus, hepatitis B virus, hepatitis C virus, Mycobacterium causing tuberculosis, poliovirus and smallpox virus. An example of one of the preferred antigens that can be used in the pharmaceutical compositions of the present invention is a SARS-CoV polyamino acid. An example of a SARS-CoV polyamino acid is the peptide SARS-CoV SC-1 (also known as CP-1, GenBank, accession number: AY274119). Another example of one of the preferred antigens is a HIV-1-CD4 polyamino acid. An example of a HIV-1-CD4 polyamino acid is the HIV-1-CD4 FLSC polypeptide. (Fouts et al., "Expression and characterization of a single-chain polypeptide analogue of the human immunodeficiency virus type 1 gpl20-CD4 receptor complex" J ". Virol. 74: 11427-11436 (2000).) An example of another Preferred antigen is derived from E6 and E7 proteins of human papillomavirus (HPV), in particular HPV-16 antigens for use in the present invention can also be derived from allergens.Most of the allergens are small proteins or substances linked to proteins that are capable of producing hyper-sensitivity Examples of allergens include animal excrement, plants, e.g., ryegrass, ragweed, Timothy grass, birches, etc., product of insects, e.g. , venom, mites, etc., food, egg albumin, and various other environmental sources.The antigens also include polyamino acids native to the mammal being treated.Such auto-polyamino acids include, for example, antigens associated with t Examples of such antigens include proteins derived from growth factors, growth factor receptors, and proteins encoded by oncogenes. Examples of growth factor receptors include EGF receptors (HERI, HER2, HER3 and HER4), including the Neu protein associated with breast tumors, and the growth factor transferin, e.g., p97. Examples of proteins encoded by oncogenes include oncofetal tumor antigens, e.g., alpha-fetoprotein and carcinoembryonic antigen. The oncofetal antigens associated with melanoma include MACE-1, MAGE-3, BEGE, GAGE-1, and GAGE-2. Alternatively, whole levigated tumor cells can be used, thereby producing vaccines comprising a collection of antigens. Examples include cells levigated from human melanoma cell lines and from human prostate cell lines. Whole cells can be derived from the mammal subject being treated, or they can be derived from another subject. For purposes of this description, the antigenic fraction also includes nucleic acid molecules that encode an antigen. The nucleic acid molecule is preferably in the form of a recombinant expression vector, such as, for example, a purified plasmid. After administration of the expression vector to a mammalian cell, the antigen is expressed intra-cellularly. The recombinant vectors may also contain a nucleotide sequence encoding suitable regulatory elements so as to effect the expression of the vector construct in a suitable host cell. Those skilled in the art will appreciate a variety of enhancers and promoters for use in the constructions of the invention., and that the constructs will contain the initiation, termination and control sequences for appropriate transcription and processing of the nucleic acid sequence encoding an antigen when the recombinant vector construct is introduced into a subject. The antigenic fraction and Ov-ASP can both be in the form of a protein, or they can both be in the form of a nucleic acid. If the antigenic fraction and Ov-ASP are both nucleic acids, they can both be in the same vector, or different vectors. Alternatively, the antigenic fraction can be a protein antigen and Ov-ASP can be in the form of nucleic acid; or the antigenic fraction may be in the form of nucleic acid and Ov-ASP may be a protein. Methods of Enhancing Specific Immune Responses The present invention includes methods of enhancing a specific immune response to an antigen in a mammal in need thereof. The methods comprise administering to the mammal an effective amount of Ov-ASP, or at least one subunit thereof; and an antigenic fraction. Ov-ASP, its subunits, and antigenic fractions suitable for use in the methods of the invention have been described above.

Ov-ASP, or its sub-units; and the antigenic fractions, can be co-administered separately, or as a vaccine composition or immunogenic composition, e.g. , as described before. Specific immune responses include humoral and cell-mediated. The humoral responses are mediated by means of B lymphocytes. Cell-mediated responses include the activation of T cells, including Thl, th2 and Te cells. Ov-ASP can enhance both humoral and cell-mediated responses, including Th1 and Th2 responses. Ov-ASP is particularly effective in enhancing Thl responses, which in turn enhance Te responses. Enhancing responses Thl is particularly effective for antigens associated with tumors since most such antigens are capable of inducing only transient, low frequency, low avidity T cell responses that are polarized to Th2 cells. An effective amount of Ov-ASP is an amount that potentiates a specific immune response in a mammal. Empowering a specific immune response is an increase in the magnitude of the immune response. The minimum amount of Ov-ASP is the lowest amount that potentiates a specific immune response in the mammalian subject. The maximum amount of Ov-ASP is the greatest amount that does not cause undesirable or intolerable side effects in the mammalian subject.

The potentiation of a humoral response can be determined by measuring the production of specific anti-bodies against the antigen. For example, aliquots of serum can be taken from a mammalian subject and antibody titers can be assayed during the course of an immunization program. Similarly, the presence of T cells, their effector mechanisms and / or their cytokine products can be monitored. For example, the enhancement of the Thl response can be determined by measuring the level of IFN-? cytokines The potentiation of the Th2 response can be determined by measuring the levels of IL-4 and IL-5 cytokines. In addition, the clinical conditions of the mammalian subject can be monitored with respect to their desired effect, e.g., an inhibition or prevention or treatment of a disease process. The magnitude of a specific immune response is manifested by the anti-bodies titer produced, the duration of the response, and / or the quality of the response. The magnitude of the immune response stimulated by an antigenic fraction administered together with Ov-ASP is greater than the immune response stimulated by the antigenic fraction administered alone. Preventing a disease means that either the mammal does not acquire the symptoms of a disease, or that the mammal acquires less symptoms or symptoms less severe than those which the mammal would otherwise acquire without the vaccine composition. Treating a disease means that the mammal ceases to suffer from the symptoms of the disease, or that the severity of the suffering is alleviated at least partially. Examples of infectious diseases for which the methods of the invention are effective are those diseases caused by the microorganisms listed above. Examples of diseases for which the methods of the invention are particularly effective include SARS and HIV. Examples of diseases associated with tumors that can treat and / or prevent the methods of the invention include cancers of the oral cavity and the pharynx (ie, tongue, mouth, pharynx) of the digestive system (e.g., esophagus, stomach , small intestine, colon, rectum, anus, liver, gallbladder, pancreas), respiratory system (eg, larynx, lungs), bones, joints, soft tissues, skin, melanomas, breast, organs reproductive organs (eg, cervix, endometrium, ovaries, prostate, testes), the urinary system (eg, urinary bladder, kidneys, urethra, and other urinary organs), the eye, the brain, the endocrine system (e.g., thyroid and other endocrine organs), lymphoma (e.g., Hodgkin's disease, non-Hodgkin's lymphoma), multiple myeloma, leukemia (e.g., acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia). The parameters of vaccination or administration for a particular antigen, e.g., the amount of Ov-ASP to be added to the particular antigen, the dose schedule, etc., can be determined by means of routine experimentation. For example, the total amount of a vaccine composition or immunogenic composition and the relative amounts of an antigen and Ov-ASP within a composition can be determined by testing the compositions in mammalian subjects. A low dose of the composition may initially be given to a mammalian subject and then the dose and / or the relative amounts of the protein adjuvant and the antigen may be varied while monitoring the immune response. If an inadequate vaccination or immune response is achieved, then the vaccination or administration parameters may be modified in a manner that is expected to enhance the immune response, e.g., by increasing the amount of antigen and / or Ov-ASP, forming complexes of the antigen with a carrier, conjugating the antigen with an immunogenic protein, or varying the route of administration, as is known in the art. Methods of stimulating a cellular response with cytokine secretion Another embodiment of the present invention includes a method of stimulating a cellular response with secretion of cytokines in a mammal in need thereof. The method comprises administering to the mammal an effective amount of Ov-ASP, or at least one subunit of Ov-ASP. Ov-ASP can be administered in the form of a pharmaceutical composition. The cellular response is stimulated in mammals whether or not they have been previously exposed to the parasite from which the Ov-ASP is derived. This unexpected discovery demonstrates that the stimulation of a cellular response by Ov-ASP is not an adaptive immune response (ie, not manifested by immunological memory). Instead, the cellular response is due to the stimulation of the innate immune response. An effective amount of Ov-ASP is any amount that up-regulates the aspects of eliminating the infection of the innate immune response. The up-regulation of the aspects that eliminate infection of the innate immune response include the induction of the inflammatory response, the regulation of hematopoiesis, the control of cell proliferation and differentiation, and the healing of wounds. The minimum amount of Ov-ASP is any amount that regulates these processes upwards. The maximum amount of Ov-ASP is an amount that does not cause excessive pro-inflammatory effects. The administration of Ov-ASP can be effected by administering the same protein, or by introducing a nucleic acid encoding the protein in a manner that allows the expression of the protein, as described above. The particular amount of Ov-ASP administered depends on the mammal subject being treated, the route of administration, and the pathology by which the mammal is being treated. For example, Ov-ASP can be injected into a tumor or applied to the site of a herpes virus infection to stimulate cytotoxic cellular responses that would decrease the tumor or help eliminate the viral infection. Ov-ASP stimulates regulating Thl, Th2 and Th cells via cellular responses IL-10. However, the protein predominantly stimulates Thl responses. Thl responses are especially effective in inducing anti-tumor responses. For example, Th2 polarized responses are stimulated in patients with active cancer. It has been found that successful therapy in some cancer patients has been accompanied by a shift from Th2 polarization to Th1 polarization. Additionally, since allergens induce Th2 responses, administration of Ov-ASP can be used to inhibit allergic responses by polarizing responses to Thl. Cytokines that are stimulated by Ov-ASP include interferon-gamma (IFN-?), granulocyte stimulating factor-macrophage colony (G-CSF), tumor necrosis factor-alpha (TNF-a), tumor growth factor beta (TGF-β), interleukin-10 (IL-10), or combinations thereof. Methods of vaccinating or generating an immune response against onchocerciasis Another embodiment of the present invention includes a method of vaccinating or generating an immune response against onchocerciasis in a mammal. The method comprises administering to a mammal, in need thereof, an effective amount of Ov-ASP, or immunogenic fragments of Ov-ASP. Ov-ASP can be administered by itself or with an adjuvant. Onchocerciasis, or river blindness, occurs mainly as a result of an inflammatory host response to infection with the filarial nematode Onchocerca volvulus. Transmitted by the bites of black flies of the Simuliidae family, the parasite invades the skin, subcutaneous tissues and other tissues, producing fibrous nodules. The host inflammatory response to infection with Onchocerca volvulus can manifest itself in chronic skin disease and eye injuries. An effective amount of Ov-ASP is an amount that prevents or inhibits onchocerciasis. For this purpose, it is necessary for the protein to produce cytophilic anti-bodies. The cytophilic antibodies are anti-bodies which, together with effector cells such as neutrophils, macrophages and / or eosinophils, for example, can significantly inhibit the growth of and / or kill the parasite. Growth is significantly inhibited if the inhibition is sufficient to prevent or reduce the symptoms of the disease in an infected mammal. The administration of Ov-ASP can be effected by administering the same protein, or by introducing a nucleic acid encoding the protein in a manner that allows the expression of the protein, as described above. General Methods A mammal that can benefit from the methods of the present invention can be any mammal. The categories of mammals include humans, non-human primates, livestock, domestic mammals, laboratory mammals, etc. Some examples of livestock include cows, pigs, horses, goats, other types of livestock, etc. Some examples of domestic mammals include dogs, cats, etc. Some examples of laboratory mammals include rats, mice, rabbits, guinea pigs, etc. A mammal in need of the methods of this invention includes mammals in which prevention or treatment of a disease is desired. The disease can be an infectious disease; an allergy; a disease associated with a tumor, such as cancer; and / or an auto-immune disease. The pharmaceutical and vaccine compositions of the present invention can be administered by any means insofar as the administration results in the desired immune response. Preferably, the compositions are administered intramuscularly, subcutaneously, transdermally, intranasally, transmucosally, intraocularly, intraperitoneally, orally or intravenously. Other suitable routes of administration include by inhalation, intra-tracheal, vaginal, rectal and intra-intestinal. Means of administration of the compositions include, but are not limited to, needle injection, catheter infusion, biolistic injectors, particle accelerators (i.e., "gene guns" or "needleless" pneumatic injectors, e.g. E-Jet (Vahlsing, H., and collaborators, J. "Immunol. Methods 171, 11-22 (1994)), Pigjet (Schrijver, R., and collaborators, Vaccine 15, 1908-1916 (1997)) , Biojector (Davis, H., et al., Vaccine 12, 1503-1509 (1994)), Gramzinski, R., et al., Mol. Med. 4, 109-118 (1998)), AdvantaJet, Medijector, depositories gel foam sponge, other commercially available reservoir materials (e.g., hydrogels), osmotic pumps (e.g., Alza mini-pumps), oral pharmaceutical formulations (tablets or pills) or solid suppository, topical creams for the skin, and decantation, use of polynucleotide-coated suture (Qin et al., Life Sciences 65, 2193-2203 (1999)), or topical applications as during surgery. The pharmaceutical and vaccine compositions of the present invention can be formulated according to known methods. For example, the compositions may comprise a suitable carrier. Suitable carriers include any of the standard pharmaceutically acceptable carriers, such as water, phosphate buffered saline, and aluminum hydroxide, latex particles, bentonite, liposomes, and microparticles. Suitable carriers are described, for example, in Remington's Pharmaceutical Sciences, 16a. edition, A. Osol, editor, Mack Publishing Co. , from Easton, Pennsylvania, United States (1980), and Remington's Pharmaceutical Sciences, 19a. edition, A.R. Gennaro, editor, ack Publishing Co. , Easton, Pennsylvania, United States (1995). The pharmaceutical composition can be formulated as an emulsion, a gel, a solution, a suspension, a lyophilized form, or any other form known in the art. The vaccine compositions or immunogenic compositions of the present invention may comprise adjuvants. In the embodiment where Ov-ASP is used as an adjuvant, other additional adjuvants may be included. Examples of adjuvants include muramyl peptides and the like; lymphokines, such as interferon, interleukin-1 and interleukin-6; saponins, fractions of saponins; Synthesized components of saponins; pluronic polyols; trehalose dimycolate; amine-containing compounds; cytokines; and derivatives of polysaccharides. In addition, the vaccine and pharmaceutical composition may also contain pharmaceutically acceptable additives including, for example, diluents, binders, stabilizers, and preservatives. The vaccine and pharmaceutical compositions may also comprise therapeutic ingredients. For example, suitable formulations for injection or infusion include sterile aqueous and non-aqueous injection solutions which may optionally contain anti-oxidants, buffers, bacteriostatic agents and solutes which make isotonic formulations with the blood of the intended recipient, and sterile aqueous suspensions and non-aqueous suspensions. aqueous which may include suspending agents and thickening agents. The vaccine and pharmaceutical compositions can be presented in unit dose or multi-dose containers, for example sealed vials and flasks, and can be stored in a freeze-dried condition (lyophilized) requiring only the addition of the sterile liquid carrier, for example, water for injection, immediately before use. The invention will be more fully understood in the light of the following examples. All citations of literature and patent documents are expressly incorporated by reference. EXAMPLES The examples demonstrate that rOv-ASP-1 acts as a potent immuno-modulator as well as an adjuvant. The examples also show that rOv-ASP-1 is a potent stimulator of cytokine secretion in humans, whether or not they were exposed to the parasite from which the protein was cloned. The adjuvant properties rOv-ASP-1 in mice and immuno-stimulatory activity on human leukocytes has been shown not to be due to contaminating bacterial lipopolysaccharide (LPS), also known as endotoxin. Example 1 Human cytokine responses to rOv-ASP-1 Experiments were conducted investigating immune responses to rOv-ASP-1 in human subjects living in areas of Africa endemic to Onchocerca volvulus. During these studies, it was noted that the recombinant protein stimulated potent cytokine responses from control subjects residing in the New York metropolitan area and who were never exposed to the parasite (figure 1). The recombinant protein stimulated significant production (P <0.05) of Thl-like cytokines (ie, IFN- ?, GM-CSF and TNF-) and a Th2 / T-cell regulatory cytokine (IL-10). One concern was that the residual LPS (endotoxin) derived from the E. coli bacterium in which rOv-ASP-1 was cloned could contribute to the stimulatory effect of cytokines. Even when the optimal concentration of cytokine-inducing Ov-ASP-1 (5 g / ml) proved to be negative to LPS activity in the leucogenic assay of Limulus amebocyte (LAL) (Sigma, from St. Louis, Missouri, United States) , additional action was taken to ensure that the results were not due to any residual LPS in antigen preparation. The data presented in figure 2 show that the bioactivity of rOv-ASP-1 was not due to any possible contamination by LPS since the production of cytokines by human PBMC was not affected by the presence of polymyxin B (Sigma), a inhibitor of LPS activity. ROv-ASP-1 ligation to peripheral blood mono-nuclear cells Peripheral blood mono-nuclear cells (PBMC) that bind to the recombinant protein were identified using biotin marketed rOv-ASP-1. As shown in Table 1, rOv-ASP-1 was ligated to most B cells and monocytes (> 94.5%). In addition, 14.5% of CD8 + T cells and 28.7% of NK cells were ligated to the protein. CD8 + T cells and NK cells are the feasible sources of IFN-α secretion. induced by rOv-ASP-1.

Table 1. FACS analysis of rOv-ASP-1 ligation marinated by FITC, biotinylated, to subsets of human leukocytes in PBMC.

Samples 1 and 2 were obtained from separate donors and 10,000 events were counted. The values represent the percentage of total cells arranged to a particular CD marker that were also ligated to rOv-ASP-1 marbed with FITC, biotinylated.

Responses of anti-bodies and mouse cytokines to rOv-ASP-1 While conducting experiments designed to evaluate rOv-ASP-1 as a possible candidate for onchocerciasis vaccine in humans, BALBC / cByJ mice were vaccinated with the recombinant protein alone or with adjuvants. IgG1 and IgG2a isotypes that were associated with responses of Th2 and Th1 T cells, respectively, were measured in mice. In broad terms, Th2 immune responses were active against extracellular pathogens in tissue fluids and Thl responses are most effective against pathogens that infect cells. Even without adjuvants, rOv-ASP-1 was able to stimulate high titers of anti-bodies in vaccinated mice (Table 2). The protein stimulated the anti-bodies both Th2 (IgGl) and Thl (IgG2a), with a slight Thl domain. Spleen cells were collected from these mice in order to determine cellular responses induced by rOv-ASP-1 to the protein. Spleen cells were cultured and re-stimulated in vi tro with rOv-ASP-1. Interferon-gamma (IFN-α) was measured as a marker for a Thl response. Interleukin-5 (IL-5) was measured to indicate Th2 activity. IL-10 was measured as a regulatory product of T and / or Th2 cells. The recombinant protein stimulated high levels of IFN-α secretion. from spleen cells obtained from mice injected with either PBS or rOv-ASP-1 (figure 3), involving direct induction of these cytokines in vitro. A similar release of IL-10, non-specific to antigen, also occurred. In contrast, IL-5 was produced only by the spleen cells of mice previously exposed to rOv-ASP-1, particularly by the group that received 2.5 g of rOv-ASP-1, indicating antigen specificity of the response to IL-5. 5.

Table 2. Endpoint reciprocal titers of anti-bodies IgG1 and IgG2a to rOv-ASP-1 in mice vaccinated with the protein in PBS or PBS alone. Titers were obtained using pooled serum samples (six mice per group).

Adjuvant studies in mice As rOv-ASP-1 was able to stimulate responses of high-titre anti-bodies to itself without added adjuvant, the question of whether the protein could act as an adjuvant for anti-body protein responses was investigated unrelated Chicken egg albumin, also known as ovalbumin (OVA), was used as a model antigen that does not stimulate appreciable anti-body responses when injected into mice without adjuvants. OVA was mixed with commercially prepared adjuvants, alum (Sigma) or MPL + TDM (Sigma) or with the test adjuvant, rOv-ASP-1. Five groups of mice were injected subcutaneously with commercially prepared adjuvants or, for control purposes, with OVA or with adjuvants alone. Each animal received 50 g of OVA per immunization. OVA and rOv-ASP-1 were diluted with sterile phosphate-buffered saline (PBS), free of LPS.

The mice received booster immunization after 14 days. Ten days later, serum was collected from the mice. The amounts of anti-bodies IgG in the serum were quantified by ELISA. When rOv-ASP-1 was used at 25 g / mouse, the protein (figure 4, black squares) surpassed the commercially prepared adjuvants alum and PL + TDM in potency. The anti-OVA IgGl endpoint titer using rOv-ASP-1 as an adjuvant at a rate of 25 g / mouse was 102,400. Titers obtained using MPL + TDM or alum adjuvants were 18,000 and 15,000, respectively. At the lowest concentration of rOv-ASP-1 (2.5 μg), the anti-OVA titre was 8,000. The IgG2a titers were considerably lower than those of IgGl and only rOv-ASP-1 at 25 yg induced an appreciable anti-OVA titre (25,600). To exclude any possibility of residual LPS in rOv-ASP-1 contributing to the adjuvant effects, LPS was removed from the concentrated solution (2.5 mg / ml) of rOv-ASP-1 using a Detoxi-gel system (Pierce Biotechnology, Rockford, Illinois, United States). The adjuvant character of working solutions of batches of rOv-ASP-1 free of LPS and containing LPS was compared. In Figure 5, open squares show that LPS-free rOv-ASP-1 had a better performance than the same protein prepared from LPS-containing material (Figure 5, solid circles) in increasing anti-body responses to OVA in immunized mice. The endpoint anti-bodies title was not obtained, but the differences are clear, especially with the IgG2a isotype. Therefore, LPS was eliminated as a contributing factor to the adjuvant properties of the recombinant Ov-ASP-1 protein. The cellular responses to the immunization antigen, OVA, were determined by measuring the secretion of cytokines by the spleen cells of the groups of mice sketched in Figure 4 and these results are shown in Figure 6. The production of IFN-α. Specific to OVA was observed only in mice that received the rOv-ASP-1 test adjuvant in both concentrations and also the MPL + TDM adjuvant. IL-5 was induced in response to OVA only with alum as an adjuvant and the release of IL-10 was stimulated using only commercial adjuvants but not the test adjuvant. The lack of IL-5 and IL-10 suggests a polarization to Thl predominantly of the anti-OVA immune response guided by rOv-ASP-1. EXAMPLE 2 Evaluation of the adjuvant character of rOv-ASP-1 for pathogen antigens The rOv-ASP-1 protein was tested to determine whether the protein had similar adjuvant potency for antigens derived from human pathogens, namely SARS-CoV and HIV- 1. BALBC / cByJ mice were immunized using the same batch of negative rOv-ASP-1 in LPS, as shown in Example 1, but mixed with 50 pg of the peptide SARC-CoV CP-1 (SC-1) or the HIV polypeptide -1-CD4 FLSC (FLSC) instead of OVA. All immunized mice received two boosters this time to optimize the response, ie a total of three injections of SC-1 or FLSC with rOv-ASP-1 as the test adjuvant or MPL + TDM as control. Using OVA as the control antigen, the endpoint titers were around 2,096,000 and 1,024,000 when they were used as adjuvants rOv-ASP-1 and MPL + TDM, respectively. These total IgG titers were approximately 10 times higher than in Example 1, suggesting that an additional boost significantly increases the production of anti-bodies. The adjuvant character of rOv-ASP-1 for the peptide SC-1 exceeded that of MPL + TDM as judged by the IgG endpoint titers of 256,000 vs. 64,000, respectively (figure 7). The anti-FLSC endpoint IgG titers achieved using both adjuvants were equivalent (approximately 1,024,000; figure 8). The IgG isotype responses to the peptide SC-1 and the FLSC polypeptide are summarized in Table 1. The rOv-ASP-1 protein stimulated higher IgG1, IgG2a and IgG2b titers than MPL + TDM. The IgG3 titers were equally low using both adjuvants. The IgG1 titers to the FLSC polypeptide were considerably lower than those of the SC-1 peptide. MPL + TDM induced an IgG2b titer greater than FLSC than rOv-ASP-1, whereas the IgG1 and IgG3 titers were the same using both adjuvants. The most striking differences between the responses induced by rOv-ASP-1 and MPL + TDM were the lack of an IgG2a (Thl) response to SC-1 using MPL + TDM, and the IgG2a response four times higher to FLSC with rOv adjuvant -ASP-1 compared to MPL + TDM. In contrast to the antigens of SC-1 and FLSC, the anti-bodies IgG2b and IgG3 to OVA were not detectable using adjuvants either rOv-ASP-1 or MPL + TDM (data not shown). Each antigen model had a different behavior depending on the antigen, but the Thl response (IgG2a) was always higher when rOv-ASP-1 was used as an adjuvant. With FLSC as immunogen, there was a change in anti-bodies IgG2a and IgG2b between adjuvants ASP-1 and Ribi. ASP-1 favored IgG2a and Ribi increased IgG2b. IgE was not detectable using rOv-ASP-1 as an adjuvant. IgM and IgA were not tested.

Table 3. Mouse IgG isotype titers, reciprocal, end-point, to FLSC or CP-1 antigens formulated with either the rOv-ASP-1 adjuvant or MPL + TDM adjuvant. rOv-ASP-1 induced much greater IgG2a antibodies (Thl) to both antigens and polarized IgGl (Th2) to the peptide SC-1.

Claims (74)

1. CLAIMS 1. An immunogenic composition, comprising: an antigenic fraction; and an adjuvant comprising an effective amount of Ov-ASP, or at least one active subunit of Ov-ASP. The composition according to claim 1, wherein the Ov-ASP sequence is shown in SEQ ID NO: 1. 3. The composition according to claim 1, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 1. 4. The composition according to claim 1, wherein the Ov-ASP sequence is shown in SEQ ID NO: 2. 5. The composition according to claim 1 , wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 2. 6. The composition according to claim 1, wherein the Ov-ASP sequence is shown in SEQ ID NO: 3. The composition according to claim 1, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 3. The composition according to claim 1, wherein the fraction antigenic is a polyamino acid, a lipid, a lipopolysaccharide, a polysaccharide, or a nucleic acid molecule that in a sequence that encodes an antigen. 9. The composition according to claim 8, wherein the antigenic fraction is a polyamino acid. The composition according to claim 1, wherein the composition is a prophylactic vaccine. 11. The composition according to claim 1, wherein the composition is a therapeutic vaccine. 12. The composition according to claim 1, wherein the immune response is a humoral response. The composition according to claim 1, wherein the immune response is a cell-mediated response. The composition according to claim 13, wherein the cell-mediated response is a Thl response. 15. The composition according to claim 13, wherein the cell-mediated response is a Th2 response. 16. The composition according to claim 13, wherein the cell-mediated response is a Th1 and Th2 response. The composition according to claim 1, wherein the ratio by weight of the antigenic fraction to Ov-ASP is from about 4: 1 to about 1: 1. The composition according to claim 1, wherein the ratio by weight of the antigenic fraction to Ov-ASP is from about 4: 1 to about 1: 4. 19. The composition according to claim 1, wherein the antigenic fraction is a SARS-CoV polyamino acid. The composition according to claim 19, wherein the SARS-CoV polyamino acid is the SARS-CoV SC-1 peptide. 21. The composition according to claim 1, wherein the antigenic fraction is an HIV-1 polyamino acid. 22. The composition according to claim 21, wherein the HIV-1 polyamino acid is the HIV-1-CD4 FLSC polypeptide. 23. A method for enhancing a specific immune response to an antigen in a mammal in need thereof, the method comprising administering to the mammal an effective amount of Ov-ASP, or at least one active subunit of Ov-ASP, and a fraction antigenic The method of claim 23, wherein the Ov-ASP sequence is shown in SEQ ID NO: 1. 25. The method according to claim 23, wherein the Ov-ASP sequence is at least about 90 % identical to SEQ ID NO: 1. 26. The method according to claim 23, wherein the Ov-ASP sequence is shown in SEQ ID NO: 2. 27. The method according to claim 23, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 2. 28. The method according to claim 23, wherein the Ov-ASP sequence is shown in SEQ ID NO: 3. 29. The method according to claim 23, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 3. 30. The method according to claim 23, wherein the antigenic fraction is a polyamino acid, a lipid, a lipopolysaccharide, a polysaccharide, or a nucleic acid molecule comprising a sequence encoding an antigen. 31. The method according to claim 30, wherein the antigenic fraction is a polyamino acid. 32. The method according to claim 23, wherein the immune response is a humoral response. 33. The method according to claim 23, wherein the immune response is a cell-mediated response. 34. The method according to claim 33, wherein the cell-mediated response is a Thl response. 35. The method according to claim 33, wherein the cell-mediated response is a Th2 response. 36. The method according to claim 33, wherein the cell mediated response is a Thl and Th2 response. 37. The method according to claim 23, wherein the antigenic fraction is a SARS-CoV polyamino acid. 38. The method according to claim 37, wherein the SARS-CoV polyamino acid is the SARS-CoV SC-1 peptide. 39. The method according to claim 23, wherein the antigenic fraction is an HIV-1 polyamino acid. 40. The method according to claim 39, wherein the HIV-1 polyamino acid is the HIV-1-CD4 FLSC polypeptide. 41. The method according to claim 23, wherein the weight ratio of the antigenic fraction to Ov-ASP is from about 4: 1 to about 1: 1. 42. The method according to claim 23, wherein the ratio by weight of the antigenic fraction to Ov-ASP is from about 4: 1 to about 1: 4. 43. A method for stimulating a cellular response with cytokine secretion in a mammal in need thereof, the method comprising administering to the mammal an effective amount of Ov-ASP, or at least one active subunit of Ov-ASP, where it is stimulated the secretion of cytokines. 44. The method according to claim 43, wherein the Ov-ASP sequence is shown in SEQ ID NO: 1. 45. The method according to claim 43, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 1. 46. The method according to claim 43, wherein the Ov-ASP sequence is shown in SEQ ID NO: 2. 47. The method according to claim 43 , wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 2. 48. The method according to claim 43, wherein the Ov-ASP sequence is shown in SEQ ID NO: 3. 49. The method according to claim 43, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 3. 50. The method according to claim 43, wherein the cytokine is IFN - ?, GM-CSF, TNF-a, IL-10, TGF-β, or combinations thereof. 51. A method of generating an immune response in a mammal in need thereof against onchocerciasis, the method comprising administering to the mammal an effective amount of Ov-ASP, or antigenic fragments of Ov-ASP, and a pharmaceutically acceptable carrier. 52. The method according to claim 51, wherein the Ov-ASP sequence is shown in SEQ ID NO: 1. 53. The method according to claim 51, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: l. 54. The method according to claim 51, wherein the Ov-ASP sequence is shown in SEQ ID NO: 2. 55. The method according to claim 51, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 2. 56. The method according to claim 51, wherein the Ov-ASP sequence is shown in SEQ ID NO: 3. 57. The method according to claim 51 , wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 3. 58. The method according to claim 51, further comprising the administration of an adjuvant. 59. A method of preventing SARS in a mammal in need thereof, the method comprising administering to the mammal an immunogenic composition comprising a SARS-CoV polyamino acid, and an effective amount of Ov-ASP, or at least one subunit of Ov. -ASP. 60. The method according to claim 59, wherein the SARS-CoV polyamino acid is the SARS-CoV SC-1 peptide. 61. The method according to claim 59, wherein the Ov-ASP sequence is shown in SEQ ID NO: 1. 62. The method according to claim 59, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 1. 63. The method according to claim 59, wherein the Ov-ASP sequence is shown in SEQ ID NO: 2. 64. The method according to claim 59 , wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 2. 65. The method according to claim 59, wherein the Ov-ASP sequence is shown in SEQ ID NO: 3. The method according to claim 59, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 3. 67. A method of preventing HIV in a mammal in need, the method comprising administering to the mammal an immunogenic composition comprising an HIV-1 polyamino acid, and an effective amount of Ov-ASP, or at least one sub-unit of Ov-ASP. 68. The method according to claim 67, wherein the HIV-1 polyamino acid is the HIV-1-CD4 FLSC polypeptide. 69. The method according to claim 67, wherein the Ov-ASP sequence is shown in SEQ ID NO: 1. 70. The method according to claim 67, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: l. 71. The method according to claim 67, wherein the Ov-ASP sequence is shown in SEQ ID NO: 2. 72. The method according to claim 67, wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 2. 73. The method according to claim 67, wherein the Ov-ASP sequence is shown in SEQ ID NO: 3. 74. The method according to claim 67 , wherein the Ov-ASP sequence is at least about 90% identical to SEQ ID NO: 3.