JPH05503851A - Neutralizing and/or ADCC Mediating Monoclonal HIV Antibodies - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] The present invention provides a monoclonal antibody (M ab), this Mab neutralizes HIV and/or inhibits antibody dependence on HIV. Mediates persistent cell-mediated cytotoxic effects.

Human immunodeficiency virus type 1 (HIV-1) induces gradual degeneration of the immune system. emanate. The most serious consequence of immunological abnormalities, acquired immunodeficiency syndrome (AIDS), is , first reported in 1981 (Gottlieb et al., New Engl. , J. Med, 305:1425.1981).

In 1983, during the search for the cause of AIDS, a new A unique retrovirus has been isolated and subsequently identified as an AIDS infection or AIDS risk. A large series of viruses have been isolated from patients in Barre-3 ssi et al., 5science 220:868, 1983; Galto et al., 5c ience 224:500.1984). This virus is non-transforming, It was identified as a cytolytic retrovirus.

The number of patients with immunodeficiency syndromes is rapidly increasing (Centers for r　Disease Control. MWR, 1983-1989). AlO3 The cases are mainly male homosexuals (H8), intravenous drug addicts and blood product addicts. An increase was reported between recipe ends. death.

However, sexual infections among heterosexual groups are also increasing. In 1983, A.I. DS has been shown to be prevalent in heterosexual groups in parts of Africa. became. AIDS is now recognized in all regions of the world and is recognized by the World Health Organization (WH). As of the end of 1989, the number of AIDS cases reported in Japan was 203,000. It has reached more than Å. More than % of these people have already died from this disease and are reported The number of cases continues to rise. The infection is spreading globally and has previously been spared. It is also attacking other countries, such as Asia. Already infected with HIV and in the future The number of patients who are likely to develop lO3 is estimated to be between 3 million and 10 million.

HIV-1 seropositive patients are often asymptomatic for several years, but some patients rapidly progresses to AIDS. A common finding in patients with HIV-1 infection is persistent Systemic lymph node disease (PGL). Opportunistic infections and Mortality due to immunodeficiency is high. Immunology in which all patients demonstrate suppression of cell-mediated immunity have physical disabilities. The most prominent immunological abnormality is the CD4+ subset of T lymphocytes. has almost completely disappeared (Haseltine, J., AIDS 1:217.1988).

AIDS is the final stage of HIV-1 infection. AIDS for people infected with HIV-1 The rate of progression increases over time, with approximately (9)% of people infected with HIV-1 remaining infected for more than 7 years. It is estimated that he will develop AIDS within the next few years. AIDS causes fatigue, diarrhea, and weight loss It begins with a number of nonspecific symptoms, such as and fever. of HIV-1 infection In the later stages, viral or fungal infections can also be seen on the skin or mucous membranes. Sara In addition, HIV-1 can also infect the central nervous system and cause neurological symptoms (Na Ann, Neurol, 19:517.1986). HIV- 1. Because of the long course of infection, it is important to intervene at an early stage.

One effective method is to develop antibodies that can prevent the spread of the virus. .

Research in the field of HIV, especially its final stage of infection, AIDS, has progressed over the past 10 years. , has been carried out intensively. However, for example, in the diagnosis and treatment of HIV In this regard, there is still a great need for improvement. Protection against HIV infection, Vaccines, for example, are of course desperately needed.

1-11 The V virus belongs to retroviruses and therefore its genetic material is R It is NA. Different types and strains of H1 viruses have been discovered. sand In addition to HIV-1, which is involved in the major AIDS epidemic, The AIDS virus, clearly similar to HIV-1 and named HIV-2, It has been discovered. Therefore, the present invention primarily relates to HIV-1 and parts thereof. strains specifically mentioned herein. It is not limited to the HIV virus, but relates generally to the HIV virus.

HIV infection occurs when HIV is infected on target cells, usually lymphocytes or macrophages. It begins when it binds to a receptor molecule called CD4. This binding is caused by CD4 g When interacting with a glycosylated protein of the H1 envelope called p120 It happens. The virus particle then undergoes endocytosis (first The membrane envelops the bound virus particles) or enters the cell by fusion, and this The process involves a second glycoprotein on the envelope called gp41.

These envelope proteins, gp120 and gp41, are derived from the precursor glycoprotein g Formed by cleavage of p160 (Haseltinel, AIDS 1 :217.1988). At the end of the HIV replication cycle, it undergoes processing. The viral proteins and genomic RNA assemble at the cell membrane and then bud from the infected cell. Virus particles are released. At that point, the viral envelope protein The protein gp120 can undergo antibody neutralization, thereby reducing C on host cells. Viral binding to D4 is prevented. Furthermore, infected cells are antibody-dependent cells. Sensitive to cell-mediated cytotoxicity (AOCC).

The outer envelope proteins, gp120 and gp41, are found in HIV-1 proteins. It shows the strongest variability (Wong-8taal et al., 5science 229 Near 59.1985). However, within gp120 there are alternating, conservative The existence of a variable region and a hypervariable region was revealed. code gpi20 Within the region, there are four hypervariable regions and five highly conserved regions. All All cysteine residues are present in all HIV-1 strains sequenced to date. have been shown to be conserved, suggesting a common three-dimensional structure. It is something.

HIV-1 envelope proteins interact with receptors, have cytopathic effects and Plays a major role in the development of humoral and cell-mediated immune responses. functional and Some of the immunological envelope sites are mapped.

A monoclonal antibody against the envelope protein of the kowara may be used to treat HIV infection. It can naturally be expected that this method will be extremely useful for medical and diagnostic purposes.

HIV type 1 (HIV-1) that can prevent virus infection in vitro Specific neutralizing antibodies have been reported (Robert-Guroff, M., M, Brown & R, C, Gal to, Nature (London ) 316:72-74.7985: Weiss, R, A,, P, C lapham, J. Weber, R. bhe insong-Popov .

A. Dalgleish, A. Carne, 1. Wel ler & R, S, Tedder, Nature (Mr. Londo @316:69 -72.1985) However, the protective role of these antibodies against H1 infection in humans is controversial. be.

Several groups of researchers conducted g120 (Ho, D, D, , J, C, Kao t an, 1. E, Rackauskas & M, EA Gurney.

5science 239: 1021-1023.1988: Matsush ita, S., M., Robert-Guroff, J., RuTche, A.

Koi to, T, Hattor i, H, Ho5h ino, J, Javaher ian, K, Takatsuki & @S, Putne y, J., Virot.

62:2107-2114. 1988: Pa1ker, T. J. M, E C1ark, A, Langlois, TA J, Matt hews, K., J.

Weinho ld, R, R, Randal l, D, 1. So f ognesi 8 B, F, Haynes, ProcA Nat 1.　 Acad, Sc i, USA.

85°1923-1936.1986: Putney, S, D,, T , J. Matthews, 'f1. G, Robe A D, L L ynn, M, Robert-Guroff, 'f1. T, Muel ler, A., Langlois, J., Ghrayeb, S., R.P. ettewa凵A K, J, Wetnhold, P, J.

Fischinger, F. Wong-8taa1.　R,C,Gal　 o & D, P, Bolognesi, 5cienc■@234°139 2-1395° 1986>, gp4T (Kennedy, R, C,, G, Drees man, T, C, Chanh, R, Bowe l 1D J, S, A l l an, T, H, Lee.

IJ, Es5ex, J, T, SDarrow, 0. D, Ha & P, Kan da, J, Biol, Chem, 262:5769-57V4.1986) and gp17 (Papsidero, LD, , M, 5heu & F, W, Ru5cett i, J, Vi rol, @69:267-2 72.1989) It has been reported that HIV-1 neutralizing antibodies can be produced against various regions of the virus.

One major site that can induce neutralizing antibodies has been described as the hypervariable loop of gp120. (Goudsmit, J., C.Debouck, R.Meloen , LSmit, M. Bakker, D.M., AsherA^,v.

Wolff, C.J., Giggs & D.C., GaJdusek, P. roc, Nat 1. Acad, Sc i, IJs■W5:4478 -44821988: Ru5che, J.A., KJavaherian, C. , McDanal, J., Petro, 0. LLynn, R, Grimaila , @A.

Langlois, R.C., Ga1lo, L.O.L. Arthur, P.J. Fischtnger, 0. P, 8o1ognesi, r, Putney & T, J, Matthews, Proc, Nat 1. Acad, Sc i, USA, 85:3198-3202.19W8).

Several types of neutralizing monoclonal antibodies (Mab) have been produced (Matsush Ita, S,.

M, Robert-Guroff, J, Ruche, A, Koito, T, Hattori, H, Ho5hino, K, Jav≠■■Nitsuya≠Mr. B K., Takatsuki & S., Putney, J., Viol, 62 :2107-2114, 1988; 5kinner, MA A, , R, Ting, A.

Langlois, K., J., Weinhold, K., Lyer. , K, Javaherian & T, J, Ms 狽■■Next sword A A IDS Res, Hum.

Retroviruses 4:187-197.1988), Mab-mediated AD CC has not been reported so far.

Most of these reports concern multivalent antibodies rather than monoclonal antibodies. It only has the ability to neutralize viruses. antibody-dependent cell-mediated Until now, monoclonal antibodies that mediate both cytotoxicity (AOCC) and neutralization have has not been disclosed.

The present invention shows reactivity with human immunodeficiency virus (HIV) and has the ability to neutralize and neutralize HIV. and/or are characterized by mediating antibody-dependent cell-mediated cytotoxicity against HIV. an intact or substantially intact monoclonal antibody, or The idiotype contains a polypeptide portion of .

In a preferred embodiment, the monoclonal antibodies of the invention have neutralizing as well as A Mediates between both DCCs.

The H(reactive monoclonal antibody) of the present invention is further characterized by a monoclonal antibody. The antigenic determinant recognized is envelope protein, gp120. gD41 or g It is characterized by being an epitope region of p17.

According to a suitable embodiment, the monoclonal antibody is specific for HIV-1 and The monoclonal antibodies of the invention are of uramammalian origin. They are preferably Fungi, especially mouse monoclonal antibodies. Variable dosing with effective reactivity main can still be introduced into the human 1g framework (Riechma n et al.

Nature Ha 2:323.1988), as well as major human isotypes and chimeric antibodies. (Morrison et al., Proc, Nat 1. Ac ad, Sc i, 81:6853.1984; 5 oul 1 anne ANature 312: 643, 1984; Neuberger et al. Nature 312:604.1 984).

The method for producing the monoclonal antibody of the present invention generally involves using mammals, preferably mammals. HIV still contains some of its envelope proteins, such as gp120. Lymphocytes like pancreatic cells from immunized and immunized mice using as immunogen Hybridoma cells are produced by fusion with myeloma cells, and the fused cells are Koehler & Mistein, Natu re 256:495.1975), solid-phase enzyme-linked immunoassay (ELISA) ) to screen antibody-producing cells and identify antibody-producing cells, i.e., hybridomas. clone and expand the hybridoma in mouse ascites or culture media. Included are methods of producing monoclonal antibodies by culturing.

The monoclonal antibodies of the present invention can be used to treat HIV infection and prevent the spread of the infection. can be used as an active ingredient in pharmaceutical compositions for Suitable for use with diluents.

According to another aspect of the invention, the monoclonal antibody is For example, blood may contain HIV antigens such as gp120 or its molecules in serum. It can be used in a diagnostic system to test the existence of columns. This kind of system odor The antibody may include an indicating means that selectively binds to the antibody when introduced into the sample. can be done.

Another aspect of the invention is the use of a monoclonal antibody of the invention, or a portion thereof, in H1 infection. as an active or passive vaccine against or producing anti-idiotypic antibodies. It is used as an immunogen for the purpose of sterilization.

Yet another aspect of the present invention is a monoclonal antibody of the present invention or a fraction thereof. For example, quality checks during pre-valuation used in immunizations such as As a key, it is used in systems to identify neutralizing epitopes.

The Mab of the invention has antibody-dependent cell-mediated cytotoxicity (AOCC) activity and neutralizing ability. characterized by

ADCC killing of virus-infected cells is due to FC reception of immunoglobulin (1g). It depends on effector cells that have a body and bind to and damage target cells coated with 1g. Ru. The ADCC killing effect in normal blood is largely due to the specific FC receptor for IgG. mediated by natural killer cells (NK) expressing the condition (Ljung gren et al.

J, tmmuno 1. Meth, 104 Near, 1987). i.e. , ADCC killing is due to a combination of humoral adaptation and cellular non-adaptive immunity. expressed and is an important means of limiting the spread of viral infections.

AC) Mono having active sites for CC activity or efficient ADCC reactivity No clonal antibodies have been reported so far.

Until now, neutralizing antibodies against viral antigens have been developed in most patients infected with viruses. It showed a protective effect on patients, and was effective in preventing viral infection through prophylaxis. Therefore Therefore, it was thought that it would have a similar beneficial effect on the clinical course of H1 infection. Dew. Antibodies attach to virus particles, which are then inactivated and become sensitive to cells. Does not show stainability HIV-1 gp120. Numerous neutralizing epitopes on gp41 and p17 Defined. Of particular interest is the immunological dominance of gp120. loop, which has been shown to induce type-specific neutralizing antibodies. (Rusche et al.

Proc, Natl, Acad, Sci, USA 85:3198.1988: Goudsmit et al., AIDS 2:157.1988)B polyclonal antisera raised in animals against various HIV-1 specific antigens. There are several studies regarding this. Some regions of gp120 and gp41 Unlike immunization with synthetic peptides that can generate neutralizing antibodies against Neutralizing antiserum raised against virus particles, purified go120 or recombinant products usually recognizes one single region within the three domains. Epitopes of HIV-1 , gp120 differential neutralization patterns are easily understood (Skinner et al., AI DS Res, Hum, Retroviruses 4:187.1988) . The second Mab also shows only type-specific reactivity. This epitope is a hypervariable region (Matsush et al., J. Virol, 62:2107 ．． 1988>. Thomas et al. have identified several species with neutralizing activity directed toward gp120. Mab, but does not mention any further specificity (AI DS 2:25.1988>.

Unlike these prior art Mab, the cross-reactive Mab of the present invention It is directed only towards amino acids and only a few amino acids can be exchanged.

The following illustrative examples disclose the present invention in terms of suitable embodiments thereof, The invention is not limited to these embodiments.

These embodiments will be explained with reference to the attached drawings, but FIG. FIG. 2 is a diagram showing the ADCC of two Mab of the present invention, and FIG. Peptide blocking ELISA is shown and Figure 3 shows the epitope for various Mabs of the invention. An example of tope mapping is given.

Example 1° Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) ADCC Assay ggren et al., J. tmmunol. Meth, 104 near (198 power It was carried out according to the instructions. Target cells are constantly infected with HTLV-[8. The monocytoid cell line U937. Clone 2 was used. As effector cells, Peripheral blood mononuclear cells (PBMC) obtained from HIV antibody-negative blood donors were used. . PBMC were mixed with antibody dilutions. After 3 hours, the upper groove was harvested and released. Radioactivity was calculated. Natural emissions do not exceed 10%. Known ADCC power Mab P41010, an HIV-reactive Mab with high titer, has clear ADCC reactivity. However, it has been shown that Mab F58/H3 does not have this specific activity. Ru.

Example 2 Neutralization (NT) Viral supernatant (reverse transcriptase activity 80.000C~/ml>100μm) was added to Example 3. After washing for the preparation times, 10% fetal bovine serum, 1% glutamine, 2.5 μs /m I in RPM1-1640 medium supplemented with polybrene and antibiotics. It was cultured for 8 days. Supernatants were collected after 4 and 8 days of incubation and H! ■Antigen Analyzed by quantification. This is an indicator of the ability of Mab to inactivate HIV. play (Nunc, Roskilde, Denmark) at room temperature for 2 hours. Coat with 0 μs/ml anti-HIV immunoglobulin overnight. on each well 100 μm of supernatant was added and incubated overnight at room temperature. For antigen detection, H1- Two horseradish peroxidase conjugates that react with different epitopes of P24 An HIV antibody was used. Add the substrate, orthophenyleneamine, and absorb at 490 nm. The yield was measured. Neutralization of f)2 in the supernatant compared to five HIV seronegative controls It was defined as >I% reduction in the amount of 4 antigens. Each test includes H1 antibody-positive blood with known neutralizing titers. Includes clear water. The values obtained are shown in Table 1.

Example 3: Production of HIV-1 monoclonal antibody H+V envelope used as immunogen Rope gp120 was detected in the culture medium of H9 cell-infected HIV-1 (HTLV-fflB). (Pot) OViC, 5science 224:497.1984 ) ONMR1 mouse (National Veterinary In5tit ute, Uppsala, Sweden) to Japan O＼Freund complete adjuva immunization with 10 μg of gp120 in cytoplasmic acid and then in Freund's incomplete adjuvant. Immunization was performed with 5 μg of gp120 four times, once a month. Pancreas 4 days after the last immunization The cells were fused with cells of the sp210xAg14 mouse myeloma cell line and hypoxane Chin-aminopterin-thymidine in DMEM medium, Koehler & 1 As described by Jilstetn (Nature 256:495.1975) and selected. For each well, solid-phase enzyme-linked immunosorbent assay (E The reactivity with viral antigens was examined using LISA. Limited dilution of cells in positive wells Cloned by. Mab is produced in the ascites of Bristane-pretreated mice. , IgG DEAE Affigel Blue (Biorad.

Richmond, CA) chromatography. The fusion of these More Mabs were produced. Two new hybridoma cell lines produced The sample is dated January 16, 1990 and is from PHLS Center for A. pplied Microbiology & Re5earch, Euro pe≠■ Collection for Animal cell culture, 5 Alisbury, deposited with Great Br1tain■O The MAbs of the present invention named F58/H3 and P4/DiO have accession numbers E Deposited as CACC90011607 and CACC90041608 respectively. Ru.

Example 4 Characteristics of Mab against l-11V-1 envelope antigen with neutralizing activity Six HIV-1 anti-gp120 Mab from Example 3 and simultaneously further One species with unpredictable properties and ADCC activity is effective against HIV-1 protein. The reactivity was tested (Table 1). The titer was 6 Mab, recombinant gp160 and It was similar to OBI. In Western blot analysis, Mab was gp16 0 and gl) 120. In immunofluorescence, HIV-1gp120 Seven out of a total of six Mabs directed against HIV-1 infected cells showed positive responses to HIV-1 infected cells. A negative reaction was observed with both infected and non-infected cells.

The six Mabs were tested against the HIV strain HTLV-II [8 with titers ranging from 100 to 1000]. showed varying neutralizing activity (Table 1). Neutralization titers also vary in different target cells It was similar. Neutralizing titers against another HIV strain called 823 are shown in Table 2. .

Due to competitive inhibition, unlabeled Mab displaced another group of labeled antibodies. neutralizing activity All 6 Mabs with 100% belonged to one group.

Example 5: Analysis of epitopes in peptides For more specific epitope mapping of the gp120 region, A 15aa peptide covering the area was used. directed to gp120 from example 3 All eight Mabs reacted with the peptide on solid phase (Table 3).

The direct peptide ELISA reaction shown in Table 3 was performed using 1 μs/ml coated antigen, 1-11 Incubation for sectioning at 37°C with 00n/100μm antiserum and Horseradish peroxidase (HRP)-rabbit anti-mouse-1g conjugate (Dako pat　ts, Copenhagen.

Denmark). The substrate is orthophenylenediamine (OPD). ) or tetramethylbenzidine (TMB). Absorption is 490nm (OP D) or read at 450 nm (TMB). The absorption value (A) of 0.2 is It was used as the to-off value (average value of absorption of negative samples plus 2 standard deviations). six Mab reacts with aa304-318 peptide in direct assay and has high absorption. It showed a weaker reaction with the aa309-323 peptide. These two The overlapping amino acid sequence common to the two peptides was 1QRGPGRAFV. this These six Mabs did not react with other envelope-displayed peptides.

The peptide blocking ELISA shown in Table 3 and Figure 2 shows the absorption at A490nm. The Mab was diluted so that the value was 1.0 to 1.5. Final concentration 0.5 μs /mI peptide was incubated with an equal volume of diluted Mab at 37'C for a period of time. Ta. Coat 100 μm of this mixture onto plates (recombinant p81 or gp160). Transfer and incubate at 3'7'C for minutes. The detection system described above was applied.

Mab (D59/A2. F58/H3, Pi1012 and P41010) were all inhibited by peptides aa304-318 and aa309-323 . Mab A47/81 and G44/H7 only contain peptide aa 304-318 (Table 3 and Figure 2).

Fine mapping of regions that appear to be advantageous for Mab neutralization was performed. 7aa o An 8aa peptide with a burst was extracted from a database (Myers, Data base on Human Re-troviruses and AIDS , Los Alamos Natl, Lab, , Los Alamos ) recorded in■驍W Synthesis was carried out for various HIV-1 strains. This is a sequence important for ADCC and neutralization. was done to establish. Figure 3 shows that the sequence QRGPGR is essential for antibody reactivity. It shows that there is. Additionally, P41010 and F58/H3 are It was reactive with the peptide sequence representing the IV strain (Figure 3). This is true for these models. Noclonal antibodies may be effective in treating HIV-infected patients (passive immunoprophylaxis). means ability. The HIV strain against which the Mab was produced, HLT-IIIB The arrangement is shown in Figure 3. All six neutralizing Mabs strongly depend on the motif GPG. , the two Mabs with the highest NT titers were dependent on QRGPGR.

NTMab reacted with the central sequence of other HjV-1 isolates in a variety of ways (Fig. 3). H1 strains MN, RF, NY5. CDC4 and BRVA sequences have a strong response Mediated sex. The epitope reactivity of Mab with neutralizing ability is It is possible to limit the sequence to PGR.

Furthermore, the HIV-1 region described above induces AOCC activity. If the whole area is variable However, the neutralizing and ADCC active Mab of the present invention, P41010, is highly active among isolates. It is preserved at the same time.

Mab- of the invention, especially high titers of P4/DIO and F58/H3 Chemical reactivity indicates group-specific reactivity. This is similar to other HIV peptides The type-specific neutralization of Mab against

One Mab has the unexpected property of having both neutralizing ability and ADCC action. It is shown in Table 1. Detailed ADCC reactivity of the two monoclonal antibodies is shown in Figure 1. vinegar That is, Mab P41010 has both NT and AOCC activities, while The other five Mabs have only neutralizing activity.

In describing the invention, conventional one-letter codes for amino acids have been used. This code and common three-letter abbreviations are shown below.

Aspartic acid Asp D Glutamic acid Glu E Phenylalanine Phe F Glycine Gly Histidine His H isoleucine lte l Methionine Met M Asparagine Asn N Proline Pro P Glutamine Glu Q Arginine Arg R Tryptophan Trp W [Table 21 Neutralization of HIV strain B23 (7) F58/10 0.09 0,11 0.36 1,03os9/s io, ot　O,360,88L,.

Positive serum 0.07 0,25 0.21 0,115 Negative blood L, 46 1 , 57 L, 49 1.36 Viruses and cells 1.52 1. ．． 27 1.36 L, a value of 561.0 or more indicates no neutralization, and a value of less than 1.0 indicates neutralization.

Specific S I Cr release % Absorption at 490nm 3B RKSIRIQRGPGRAFVTIGK+Summary Human Immunodeficiency Virus (HIV) Monoclonal antibodies (Mab) against HIV that mediate persistent cell-mediated cytotoxicity , methods for producing these Mabs, and hybridomas producing these Mabs will be disclosed.

These MAbs can be used as passive or active vaccines to prevent the spread of HIV infection, Assays for H1 antigen and identification of neutralizing epitopes during immunization preparations It is of constant use.

international search report l, l+*+*mee*lAm1ejHanllz PCT/SE 91100 071+ll+,,-ma,,Ic,+-w-PC/5E91100071 country international investigation report

Claims (12)

[Claims] 1. Shows reactivity with human immunodeficiency virus (HIV) and is effective in neutralizing and/or treating HIV. or an antibody characterized by mediating antibody-dependent cell-mediated cytotoxicity against HIV. intact or substantially intact monoclonal antibodies, or polynucleotides thereof. Idiotypes containing peptide moieties. 2. Mediates both HIV neutralization and antibody-dependent cell-mediated cytotoxicity against HIV. The monoclonal antibody or a portion thereof according to claim 1, characterized in that: 3. Monoclonal antibodies of mammalian origin, preferably of rodent origin, e.g. body or parts thereof, or their combination with human frameworks The monoclonal antibody or part thereof according to "Claim 1 or 2" characterized in that Minutes. 4. HIV strain, MN, RF, NY5, CDC4, BRVA and/or HTL Claim 1 characterized in that it is reactive with HIV type 1, including V-IIIB. The monoclonal antibody or portion thereof according to item 3. 5. Cricosylated protein gp120 in the HIV envelope, suitably a peptide Sequence X1X2QRGPGRX3X4 (wherein, X1, X2, X3 and X4 are arbitrary ), or is reactive with the peptide sequence GPGR of gp120 The monoclonal antibody or the monoclonal antibody according to any one of claims 1 to 4, characterized in that is that part. 6. The monoclonal antibody or a portion thereof according to any one of "claims 1 to 5" In this case, the antibody is directed against myeloma cell lines and HIV immunogens such as HIV gp120. from a mammal, such as a mouse, immunized with an immunogen containing HIV, such as HI by fusion with lymphocytes such as spleen cells that produce antibodies that react with VGP120. Hybridomas are produced by hybridoma cells that are formed by Ridoma ECACC reception number 90011607 or ECACC reception number 900 Antibody that is 11608. 7. A hybridoma capable of producing the monoclonal antibody according to "Claim 1" Hybridoma ECCACC reception number 90011607 or hybridoma Hybridoma with ECACC reception number 90011608. 8. The monoclonal antibody according to any one of claims 1 to 6 or a portion thereof In the manufacturing method, hybridoma ECACC accession number 90011607, or 90011608, respectively, grown in mice or culture media; Recovery of monoclonal antibodies or portions thereof from mouse ascites or culture media A method characterized by: 9. of the monoclonal antibody or a portion thereof according to any one of "claims 1 to 6" of HIV infection characterized by comprising an effective amount and a physiologically tolerable diluent. How to prevent the spread. 10. A diagnostic test that assays for the presence of HIV antigens such as gp120 in biological samples. In disconnection, the monochrome according to any one of claims 1 to 6 as an active ingredient. null antibodies or portions thereof, and the monoclonal antibodies described above when introduced into the sample. system consisting of any indicating means that selectively binds the null antibody or portion thereof. 11. Active or passive vaccines or anti-idiotypes against HIV infection The model according to any one of claims 1 to 6 as an immunogen for producing antibodies. Use of noclonal antibodies or portions thereof. 12. Breparations used for immunization, e.g. in vaccines. ``Claim'' in systems for identifying Japanese epitopes, e.g. as a quality check. Use of the monoclonal antibody or a portion thereof according to any one of Items 1 to 6.