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. 1992 Jul;66(7):4464–4469. doi: 10.1128/jvi.66.7.4464-4469.1992

Neutralization of multiple laboratory and clinical isolates of human immunodeficiency virus type 1 (HIV-1) by antisera raised against gp120 from the MN isolate of HIV-1.

P W Berman 1, T J Matthews 1, L Riddle 1, M Champe 1, M R Hobbs 1, G R Nakamura 1, J Mercer 1, D J Eastman 1, C Lucas 1, A J Langlois 1, et al.
PMCID: PMC241255  PMID: 1602554

Abstract

Vaccines prepared from the envelope glycoprotein, gp120, of the common laboratory isolate of human immunodeficiency virus type 1 (HIV-1) (IIIB/LAV-1) elicit antibodies that neutralize the homologous virus but show little if any cross-neutralizing activity. This may be because the principal neutralizing determinant (PND) of gp120 is highly unusual in the IIIB/LAV-1 strain and is not representative of those found in the majority of field isolates. We have now examined the immunogenicity of recombinant gp120 prepared from the MN strain of HIV-1 (MN-rgp120), whose PND is thought to be representative of approximately 60% of the isolates in North America. Our results show that MN-rgp120 is a potent immunogen and elicits anti-gp120 titers comparable to those found in HIV-1-infected individuals. While both MN-rgp120 and IIIB-rgp120 induced antibodies able to block gp120 binding to CD4, strain-specific and type-common blocking antibodies were detected. Finally, antibodies to MN-rgp120 but not to IIIB-rgp120 were effective in neutralizing a broad range of laboratory and clinical isolates of HIV-1. These studies demonstrate that susceptibility or resistance to neutralization by antibodies to gp120 correlates with the PND sequence and suggest that the problem of antigenic variation may not be insurmountable in the development of an effective AIDS vaccine.

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Selected References

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  1. Berman P. W., Gregory T. J., Riddle L., Nakamura G. R., Champe M. A., Porter J. P., Wurm F. M., Hershberg R. D., Cobb E. K., Eichberg J. W. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature. 1990 Jun 14;345(6276):622–625. doi: 10.1038/345622a0. [DOI] [PubMed] [Google Scholar]
  2. Berman P. W., Groopman J. E., Gregory T., Clapham P. R., Weiss R. A., Ferriani R., Riddle L., Shimasaki C., Lucas C., Lasky L. A. Human immunodeficiency virus type 1 challenge of chimpanzees immunized with recombinant envelope glycoprotein gp120. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5200–5204. doi: 10.1073/pnas.85.14.5200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carrow E. W., Vujcic L. K., Glass W. L., Seamon K. B., Rastogi S. C., Hendry R. M., Boulos R., Nzila N., Quinnan G. V., Jr High prevalence of antibodies to the gp120 V3 region principal neutralizing determinant of HIV-1MN in sera from Africa and the Americas. AIDS Res Hum Retroviruses. 1991 Oct;7(10):831–838. doi: 10.1089/aid.1991.7.831. [DOI] [PubMed] [Google Scholar]
  4. Chaffee S., Leeds J. M., Matthews T. J., Weinhold K. J., Skinner M., Bolognesi D. P., Hershfield M. S. Phenotypic variation in the response to the human immunodeficiency virus among derivatives of the CEM T and WIL-2 B cell lines. J Exp Med. 1988 Aug 1;168(2):605–621. doi: 10.1084/jem.168.2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cheingsong-Popov R., Callow D., Beddows S., Shaunak S., Wasi C., Kaleebu P., Gilks C., Petrascu I. V., Garaev M. M., Watts D. M. Geographic diversity of human immunodeficiency virus type 1: serologic reactivity to env epitopes and relationship to neutralization. J Infect Dis. 1992 Feb;165(2):256–261. doi: 10.1093/infdis/165.2.256. [DOI] [PubMed] [Google Scholar]
  6. Girard M., Kieny M. P., Pinter A., Barre-Sinoussi F., Nara P., Kolbe H., Kusumi K., Chaput A., Reinhart T., Muchmore E. Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):542–546. doi: 10.1073/pnas.88.2.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goudsmit J., Debouck C., Meloen R. H., Smit L., Bakker M., Asher D. M., Wolff A. V., Gibbs C. J., Jr, Gajdusek D. C. Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4478–4482. doi: 10.1073/pnas.85.12.4478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Ho D. D., McKeating J. A., Li X. L., Moudgil T., Daar E. S., Sun N. C., Robinson J. E. Conformational epitope on gp120 important in CD4 binding and human immunodeficiency virus type 1 neutralization identified by a human monoclonal antibody. J Virol. 1991 Jan;65(1):489–493. doi: 10.1128/jvi.65.1.489-493.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. 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]
  13. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987 Sep 11;50(6):975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [PubMed] [Google Scholar]
  14. Leonard C. K., Spellman M. W., Riddle L., Harris R. J., Thomas J. N., Gregory T. J. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem. 1990 Jun 25;265(18):10373–10382. [PubMed] [Google Scholar]
  15. Matthews T. J., Langlois A. J., Robey W. G., Chang N. T., Gallo R. C., Fischinger P. J., Bolognesi D. P. Restricted neutralization of divergent human T-lymphotropic virus type III isolates by antibodies to the major envelope glycoprotein. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9709–9713. doi: 10.1073/pnas.83.24.9709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  17. Nara P. L., Robey W. G., Pyle S. W., Hatch W. C., Dunlop N. M., Bess J. W., Jr, Kelliher J. C., Arthur L. O., Fischinger P. J. Purified envelope glycoproteins from human immunodeficiency virus type 1 variants induce individual, type-specific neutralizing antibodies. J Virol. 1988 Aug;62(8):2622–2628. doi: 10.1128/jvi.62.8.2622-2628.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nara P. L., Smit L., Dunlop N., Hatch W., Merges M., Waters D., Kelliher J., Gallo R. C., Fischinger P. J., Goudsmit J. Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees. J Virol. 1990 Aug;64(8):3779–3791. doi: 10.1128/jvi.64.8.3779-3791.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Oram J. D., Downing R. G., Roff M., Serwankambo N., Clegg J. C., Featherstone A. S., Booth J. C. Sequence analysis of the V3 loop regions of the env genes of Ugandan human immunodeficiency proviruses. AIDS Res Hum Retroviruses. 1991 Jul;7(7):605–614. doi: 10.1089/aid.1991.7.605. [DOI] [PubMed] [Google Scholar]
  20. Palker T. J., Clark M. E., Langlois A. J., Matthews T. J., Weinhold K. J., Randall R. R., Bolognesi D. P., Haynes B. F. Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1932–1936. doi: 10.1073/pnas.85.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Weiss R. A., Clapham P. R., Weber J. N., Dalgleish A. G., Lasky L. A., Berman P. W. Variable and conserved neutralization antigens of human immunodeficiency virus. Nature. 1986 Dec 11;324(6097):572–575. doi: 10.1038/324572a0. [DOI] [PubMed] [Google Scholar]
  26. Zwart G., Langedijk H., van der Hoek L., de Jong J. J., Wolfs T. F., Ramautarsing C., Bakker M., de Ronde A., Goudsmit J. Immunodominance and antigenic variation of the principal neutralization domain of HIV-1. Virology. 1991 Apr;181(2):481–489. doi: 10.1016/0042-6822(91)90880-k. [DOI] [PubMed] [Google Scholar]

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