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. 1992 Dec;66(12):7538–7542. doi: 10.1128/jvi.66.12.7538-7542.1992

Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody.

M K Gorny 1, A J Conley 1, S Karwowska 1, A Buchbinder 1, J Y Xu 1, E A Emini 1, S Koenig 1, S Zolla-Pazner 1
PMCID: PMC240465  PMID: 1433529

Abstract

The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is thought to induce potent neutralizing antibodies which are generally defined as type specific and reactive with individual viral isolates. In contrast, the CD4-binding domain is thought to induce neutralizing antibodies that are group specific and capable of neutralizing all isolates of HIV-1. However, in this study, we used a panel of human monoclonal antibodies to these regions of gp120 which displays specificities and neutralizing activities that challenge these tenets. In particular, we used a human monoclonal antibody to the V3 domain with exceptionally potent and broad neutralizing activity against many diverse HIV-1 isolates. The anti-CD4-binding domain antibodies, on the other hand, showed a more restricted pattern of activity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akerblom L., Hinkula J., Broliden P. A., Mäkitalo B., Fridberger T., Rosen J., Villacres-Eriksson M., Morein B., Wahren B. Neutralizing cross-reactive and non-neutralizing monoclonal antibodies to HIV-1 gp120. AIDS. 1990 Oct;4(10):953–960. doi: 10.1097/00002030-199010000-00002. [DOI] [PubMed] [Google Scholar]
  2. Benn S., Rutledge R., Folks T., Gold J., Baker L., McCormick J., Feorino P., Piot P., Quinn T., Martin M. Genomic heterogeneity of AIDS retroviral isolates from North America and Zaire. Science. 1985 Nov 22;230(4728):949–951. doi: 10.1126/science.2997922. [DOI] [PubMed] [Google Scholar]
  3. Emini E. A., Jameson B. A., Wimmer E. Priming for and induction of anti-poliovirus neutralizing antibodies by synthetic peptides. Nature. 1983 Aug 25;304(5928):699–703. doi: 10.1038/304699a0. [DOI] [PubMed] [Google Scholar]
  4. Emini E. A., Nara P. L., Schleif W. A., Lewis J. A., Davide J. P., Lee D. R., Kessler J., Conley S., Matsushita S., Putney S. D. Antibody-mediated in vitro neutralization of human immunodeficiency virus type 1 abolishes infectivity for chimpanzees. J Virol. 1990 Aug;64(8):3674–3678. doi: 10.1128/jvi.64.8.3674-3678.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Emini E. A., Schleif W. A., Nunberg J. H., Conley A. J., Eda Y., Tokiyoshi S., Putney S. D., Matsushita S., Cobb K. E., Jett C. M. Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. Nature. 1992 Feb 20;355(6362):728–730. doi: 10.1038/355728a0. [DOI] [PubMed] [Google Scholar]
  6. Friguet B., Chaffotte A. F., Djavadi-Ohaniance L., Goldberg M. E. Measurements of the true affinity constant in solution of antigen-antibody complexes by enzyme-linked immunosorbent assay. J Immunol Methods. 1985 Mar 18;77(2):305–319. doi: 10.1016/0022-1759(85)90044-4. [DOI] [PubMed] [Google Scholar]
  7. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  8. Geysen H. M., Meloen R. H., Barteling S. J. Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci U S A. 1984 Jul;81(13):3998–4002. doi: 10.1073/pnas.81.13.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gorny M. K., Gianakakos V., Sharpe S., Zolla-Pazner S. Generation of human monoclonal antibodies to human immunodeficiency virus. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1624–1628. doi: 10.1073/pnas.86.5.1624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gorny M. K., Xu J. Y., Gianakakos V., Karwowska S., Williams C., Sheppard H. W., Hanson C. V., Zolla-Pazner S. Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3238–3242. doi: 10.1073/pnas.88.8.3238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goudsmit J., Boucher C. A., Meloen R. H., Epstein L. G., Smit L., van der Hoek L., Bakker M. Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition. AIDS. 1988 Jun;2(3):157–164. [PubMed] [Google Scholar]
  12. Hahn B. H., Shaw G. M., Taylor M. E., Redfield R. R., Markham P. D., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Parks E. S., Parks W. P. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986 Jun 20;232(4757):1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
  13. Haigwood N. L., Nara P. L., Brooks E., Van Nest G. A., Ott G., Higgins K. W., Dunlop N., Scandella C. J., Eichberg J. W., Steimer K. S. Native but not denatured recombinant human immunodeficiency virus type 1 gp120 generates broad-spectrum neutralizing antibodies in baboons. J Virol. 1992 Jan;66(1):172–182. doi: 10.1128/jvi.66.1.172-182.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ho D. D., Sarngadharan M. G., Hirsch M. S., Schooley R. T., Rota T. R., Kennedy R. C., Chanh T. C., Sato V. L. Human immunodeficiency virus neutralizing antibodies recognize several conserved domains on the envelope glycoproteins. J Virol. 1987 Jun;61(6):2024–2028. doi: 10.1128/jvi.61.6.2024-2028.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Javaherian K., Langlois A. J., LaRosa G. J., Profy A. T., Bolognesi D. P., Herlihy W. C., Putney S. D., Matthews T. J. Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1. Science. 1990 Dec 14;250(4987):1590–1593. doi: 10.1126/science.1703322. [DOI] [PubMed] [Google Scholar]
  16. Javaherian K., Langlois A. J., McDanal C., Ross K. L., Eckler L. I., Jellis C. L., Profy A. T., Rusche J. R., Bolognesi D. P., Putney S. D. Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6768–6772. doi: 10.1073/pnas.86.17.6768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kang C. Y., Nara P., Chamat S., Caralli V., Ryskamp T., Haigwood N., Newman R., Köhler H. Evidence for non-V3-specific neutralizing antibodies that interfere with gp120/CD4 binding in human immunodeficiency virus 1-infected humans. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6171–6175. doi: 10.1073/pnas.88.14.6171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Karwowska S., Gorny M. K., Buchbinder A., Gianakakos V., Williams C., Fuerst T., Zolla-Pazner S. Production of human monoclonal antibodies specific for conformational and linear non-V3 epitopes of gp120. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1099–1106. doi: 10.1089/aid.1992.8.1099. [DOI] [PubMed] [Google Scholar]
  19. Kowalski M., Potz J., Basiripour L., Dorfman T., Goh W. C., Terwilliger E., Dayton A., Rosen C., Haseltine W., Sodroski J. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science. 1987 Sep 11;237(4820):1351–1355. doi: 10.1126/science.3629244. [DOI] [PubMed] [Google Scholar]
  20. LaRosa G. J., Davide J. P., Weinhold K., Waterbury J. A., Profy A. T., Lewis J. A., Langlois A. J., Dreesman G. R., Boswell R. N., Shadduck P. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science. 1990 Aug 24;249(4971):932–935. doi: 10.1126/science.2392685. [DOI] [PubMed] [Google Scholar]
  21. Lasky L. A., Groopman J. E., Fennie C. W., Benz P. M., Capon D. J., Dowbenko D. J., Nakamura G. R., Nunes W. M., Renz M. E., Berman P. W. Neutralization of the AIDS retrovirus by antibodies to a recombinant envelope glycoprotein. Science. 1986 Jul 11;233(4760):209–212. doi: 10.1126/science.3014647. [DOI] [PubMed] [Google Scholar]
  22. Levy J. A., Hoffman A. D., Kramer S. M., Landis J. A., Shimabukuro J. M., Oshiro L. S. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science. 1984 Aug 24;225(4664):840–842. doi: 10.1126/science.6206563. [DOI] [PubMed] [Google Scholar]
  23. Linsley P. S., Ledbetter J. A., Kinney-Thomas E., Hu S. L. Effects of anti-gp120 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1. J Virol. 1988 Oct;62(10):3695–3702. doi: 10.1128/jvi.62.10.3695-3702.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Matsushita S., Robert-Guroff M., Rusche J., Koito A., Hattori T., Hoshino H., Javaherian K., Takatsuki K., Putney S. Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope. J Virol. 1988 Jun;62(6):2107–2114. doi: 10.1128/jvi.62.6.2107-2114.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nara P. L., Garrity R. R., Goudsmit J. Neutralization of HIV-1: a paradox of humoral proportions. FASEB J. 1991 Jul;5(10):2437–2455. doi: 10.1096/fasebj.5.10.1712328. [DOI] [PubMed] [Google Scholar]
  26. Neurath A. R., Kent S. B., Parker K., Prince A. M., Strick N., Brotman B., Sproul P. Antibodies to a synthetic peptide from the preS 120-145 region of the hepatitis B virus envelope are virus neutralizing. Vaccine. 1986 Mar;4(1):35–37. doi: 10.1016/s0264-410x(86)80001-9. [DOI] [PubMed] [Google Scholar]
  27. Ohno T., Terada M., Yoneda Y., Shea K. W., Chambers R. F., Stroka D. M., Nakamura M., Kufe D. W. A broadly neutralizing monoclonal antibody that recognizes the V3 region of human immunodeficiency virus type 1 glycoprotein gp120. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10726–10729. doi: 10.1073/pnas.88.23.10726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Olshevsky U., Helseth E., Furman C., Li J., Haseltine W., Sodroski J. Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding. J Virol. 1990 Dec;64(12):5701–5707. doi: 10.1128/jvi.64.12.5701-5707.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  30. Posner M. R., Hideshima T., Cannon T., Mukherjee M., Mayer K. H., Byrn R. A. An IgG human monoclonal antibody that reacts with HIV-1/GP120, inhibits virus binding to cells, and neutralizes infection. J Immunol. 1991 Jun 15;146(12):4325–4332. [PubMed] [Google Scholar]
  31. Robertson G. A., Kostek B. M., Schleif W. A., Lewis J. A., Emini E. A. A microtiter cell-culture assay for the determination of anti-human immunodeficiency virus neutralizing antibody activity. J Virol Methods. 1988 Jul;20(3):195–202. doi: 10.1016/0166-0934(88)90123-1. [DOI] [PubMed] [Google Scholar]
  32. Robinson J. E., Holton D., Pacheco-Morell S., Liu J., McMurdo H. Identification of conserved and variant epitopes of human immunodeficiency virus type 1 (HIV-1) gp120 by human monoclonal antibodies produced by EBV-transformed cell lines. AIDS Res Hum Retroviruses. 1990 May;6(5):567–579. doi: 10.1089/aid.1990.6.567. [DOI] [PubMed] [Google Scholar]
  33. Rusche J. R., Javaherian K., McDanal C., Petro J., Lynn D. L., Grimaila R., Langlois A., Gallo R. C., Arthur L. O., Fischinger P. J. Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc Natl Acad Sci U S A. 1988 May;85(9):3198–3202. doi: 10.1073/pnas.85.9.3198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sato H., Hirata J., Kuroda N., Shiraki H., Maeda Y., Okochi K. Identification and mapping of neutralizing epitopes of human parvovirus B19 by using human antibodies. J Virol. 1991 Oct;65(10):5485–5490. doi: 10.1128/jvi.65.10.5485-5490.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Scott C. F., Jr, Silver S., Profy A. T., Putney S. D., Langlois A., Weinhold K., Robinson J. E. Human monoclonal antibody that recognizes the V3 region of human immunodeficiency virus gp120 and neutralizes the human T-lymphotropic virus type IIIMN strain. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8597–8601. doi: 10.1073/pnas.87.21.8597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sherry B., Mosser A. G., Colonno R. J., Rueckert R. R. Use of monoclonal antibodies to identify four neutralization immunogens on a common cold picornavirus, human rhinovirus 14. J Virol. 1986 Jan;57(1):246–257. doi: 10.1128/jvi.57.1.246-257.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Steimer K. S., Scandella C. J., Skiles P. V., Haigwood N. L. Neutralization of divergent HIV-1 isolates by conformation-dependent human antibodies to Gp120. Science. 1991 Oct 4;254(5028):105–108. doi: 10.1126/science.1718036. [DOI] [PubMed] [Google Scholar]
  38. Sun N. C., Ho D. D., Sun C. R., Liou R. S., Gordon W., Fung M. S., Li X. L., Ting R. C., Lee T. H., Chang N. T. Generation and characterization of monoclonal antibodies to the putative CD4-binding domain of human immunodeficiency virus type 1 gp120. J Virol. 1989 Sep;63(9):3579–3585. doi: 10.1128/jvi.63.9.3579-3585.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tilley S. A., Honnen W. J., Racho M. E., Hilgartner M., Pinter A. A human monoclonal antibody against the CD4-binding site of HIV1 gp120 exhibits potent, broadly neutralizing activity. Res Virol. 1991 Jul-Aug;142(4):247–259. doi: 10.1016/0923-2516(91)90010-z. [DOI] [PubMed] [Google Scholar]
  40. Wensvoort G. Topographical and functional mapping of epitopes on hog cholera virus with monoclonal antibodies. J Gen Virol. 1989 Nov;70(Pt 11):2865–2876. doi: 10.1099/0022-1317-70-11-2865. [DOI] [PubMed] [Google Scholar]
  41. Xu J. Y., Gorny M. K., Palker T., Karwowska S., Zolla-Pazner S. Epitope mapping of two immunodominant domains of gp41, the transmembrane protein of human immunodeficiency virus type 1, using ten human monoclonal antibodies. J Virol. 1991 Sep;65(9):4832–4838. doi: 10.1128/jvi.65.9.4832-4838.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

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