Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1992 Jan;66(1):172–182. doi: 10.1128/jvi.66.1.172-182.1992

Native but not denatured recombinant human immunodeficiency virus type 1 gp120 generates broad-spectrum neutralizing antibodies in baboons.

N L Haigwood 1, P L Nara 1, E Brooks 1, G A Van Nest 1, G Ott 1, K W Higgins 1, N Dunlop 1, C J Scandella 1, J W Eichberg 1, K S Steimer 1
PMCID: PMC238273  PMID: 1727480

Abstract

The protection of individuals from human immunodeficiency virus type 1 (HIV-1) infection with an envelope subunit derived from a single isolate will require the presentation of conserved epitopes in gp120. The objective of the studies presented here was to test whether a native recombinant gp120 (rgp120) immunogen would elicit responses to conserved neutralization epitopes that are not present in a denatured recombinant gp120 antigen from the same virus isolate. In a large study of 51 baboons, we have generated heterologous neutralizing activity with native, glycosylated rgp120SF2 but not with denatured, nonglycosylated env 2-3SF2. After repeated exposure to rgp120SF2 formulated with one of several adjuvants, virus isolates from the United States, the Caribbean, and Africa were neutralized. The timing of the immunization regimen and the choice of adjuvant affected the virus neutralization titers both quantitatively and qualitatively. These results suggest that vaccination with native, glycosylated rgp120 from a single virus isolate, HIV-SF2, may elicit a protective immune response effective against geographically and sequentially distinct HIV-1 isolates.

Full text

PDF
172

Selected References

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

  1. Abrignani S., Montagna D., Jeannet M., Wintsch J., Haigwood N. L., Shuster J. R., Steimer K. S., Cruchaud A., Staehelin T. Priming of CD4+ T cells specific for conserved regions of human immunodeficiency virus glycoprotein gp120 in humans immunized with a recombinant envelope protein. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6136–6140. doi: 10.1073/pnas.87.16.6136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alizon M., Wain-Hobson S., Montagnier L., Sonigo P. Genetic variability of the AIDS virus: nucleotide sequence analysis of two isolates from African patients. Cell. 1986 Jul 4;46(1):63–74. doi: 10.1016/0092-8674(86)90860-3. [DOI] [PubMed] [Google Scholar]
  3. Anderson K. P., Lucas C., Hanson C. V., Londe H. F., Izu A., Gregory T., Ammann A., Berman P. W., Eichberg J. W. Effect of dose and immunization schedule on immune response of baboons to recombinant glycoprotein 120 of HIV-1. J Infect Dis. 1989 Dec;160(6):960–969. doi: 10.1093/infdis/160.6.960. [DOI] [PubMed] [Google Scholar]
  4. Arthur L. O., Bess J. W., Jr, Waters D. J., Pyle S. W., Kelliher J. C., Nara P. L., Krohn K., Robey W. G., Langlois A. J., Gallo R. C. Challenge of chimpanzees (Pan troglodytes) immunized with human immunodeficiency virus envelope glycoprotein gp120. J Virol. 1989 Dec;63(12):5046–5053. doi: 10.1128/jvi.63.12.5046-5053.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arthur L. O., Pyle S. W., Nara P. L., Bess J. W., Jr, Gonda M. A., Kelliher J. C., Gilden R. V., Robey W. G., Bolognesi D. P., Gallo R. C. Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8583–8587. doi: 10.1073/pnas.84.23.8583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Banks T., Huo B., Kousoulas K., Spaete R., Pachl C., Pereira L. A major neutralizing domain maps within the carboxyl-terminal half of the cleaved cytomegalovirus B glycoprotein. J Gen Virol. 1989 Apr;70(Pt 4):979–985. doi: 10.1099/0022-1317-70-4-979. [DOI] [PubMed] [Google Scholar]
  7. Berkower I., Smith G. E., Giri C., Murphy D. Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation. J Exp Med. 1989 Nov 1;170(5):1681–1695. doi: 10.1084/jem.170.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Clements G. J., Price-Jones M. J., Stephens P. E., Sutton C., Schulz T. F., Clapham P. R., McKeating J. A., McClure M. O., Thomson S., Marsh M. The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: a possible function in viral fusion? AIDS Res Hum Retroviruses. 1991 Jan;7(1):3–16. doi: 10.1089/aid.1991.7.3. [DOI] [PubMed] [Google Scholar]
  11. Desai S. M., Kalyanaraman V. S., Casey J. M., Srinivasan A., Andersen P. R., Devare S. G. Molecular cloning and primary nucleotide sequence analysis of a distinct human immunodeficiency virus isolate reveal significant divergence in its genomic sequences. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8380–8384. doi: 10.1073/pnas.83.21.8380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Goudsmit J. Immunodominant B-cell epitopes of the HIV-1 envelope recognized by infected and immunized hosts. AIDS. 1988;2 (Suppl 1):S41–S45. doi: 10.1097/00002030-198800001-00006. [DOI] [PubMed] [Google Scholar]
  15. Goudsmit J., Thiriart C., Smit L., Bruck C., Gibbs C. J. Temporal development of cross-neutralization between HTLV-III B and HTLV-III RF in experimentally infected chimpanzees. Vaccine. 1988 Jun;6(3):229–232. doi: 10.1016/0264-410x(88)90216-2. [DOI] [PubMed] [Google Scholar]
  16. Haigwood N. L., Shuster J. R., Moore G. K., Lee H., Skiles P. V., Higgins K. W., Barr P. J., George-Nascimento C., Steimer K. S. Importance of hypervariable regions of HIV-1 gp120 in the generation of virus neutralizing antibodies. AIDS Res Hum Retroviruses. 1990 Jul;6(7):855–869. doi: 10.1089/aid.1990.6.855. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. Katzenstein D. A., Vujcic L. K., Latif A., Boulos R., Halsey N. A., Quinn T. C., Rastogi S. C., Quinnan G. V., Jr Human immunodeficiency virus neutralizing antibodies in sera from North Americans and Africans. J Acquir Immune Defic Syndr. 1990;3(8):810–816. [PubMed] [Google Scholar]
  21. Klaniecki J., Dykers T., Travis B., Schmitt R., Wain M., Watson A., Sridhar P., McClure J., Morein B., Ulrich J. T. Cross-neutralizing antibodies in rabbits immunized with HIV-1 gp160 purified from simian cells infected with a recombinant vaccinia virus. AIDS Res Hum Retroviruses. 1991 Oct;7(10):791–798. doi: 10.1089/aid.1991.7.791. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Lidgate D. M., Fu R. C., Byars N. E., Foster L. C., Fleitman J. S. Formulation of vaccine adjuvant muramyldipeptides. 3. Processing optimization, characterization, and bioactivity of an emulsion vehicle. Pharm Res. 1989 Sep;6(9):748–752. doi: 10.1023/a:1015915212195. [DOI] [PubMed] [Google Scholar]
  25. McDougal J. S., Nicholson J. K., Cross G. D., Cort S. P., Kennedy M. S., Mawle A. C. Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. J Immunol. 1986 Nov 1;137(9):2937–2944. [PubMed] [Google Scholar]
  26. Nara P. L., Hatch W. C., Dunlop N. M., Robey W. G., Arthur L. O., Gonda M. A., Fischinger P. J. Simple, rapid, quantitative, syncytium-forming microassay for the detection of human immunodeficiency virus neutralizing antibody. AIDS Res Hum Retroviruses. 1987 Fall;3(3):283–302. doi: 10.1089/aid.1987.3.283. [DOI] [PubMed] [Google Scholar]
  27. Nara P. L., Robey W. G., Arthur L. O., Asher D. M., Wolff A. V., Gibbs C. J., Jr, Gajdusek D. C., Fischinger P. J. Persistent infection of chimpanzees with human immunodeficiency virus: serological responses and properties of reisolated viruses. J Virol. 1987 Oct;61(10):3173–3180. doi: 10.1128/jvi.61.10.3173-3180.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. 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]
  31. 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]
  32. Putney S. D., Matthews T. J., Robey W. G., Lynn D. L., Robert-Guroff M., Mueller W. T., Langlois A. J., Ghrayeb J., Petteway S. R., Jr, Weinhold K. J. HTLV-III/LAV-neutralizing antibodies to an E. coli-produced fragment of the virus envelope. Science. 1986 Dec 12;234(4782):1392–1395. doi: 10.1126/science.2431482. [DOI] [PubMed] [Google Scholar]
  33. Pyle S. W., Morein B., Bess J. W., Jr, Akerblom L., Nara P. L., Nigida S. M., Jr, Lerche N. W., Robey W. G., Fischinger P. J., Arthur L. O. Immune response to immunostimulatory complexes (ISCOMs) prepared from human immunodeficiency virus type 1 (HIV-1) or the HIV-1 external envelope glycoprotein (gp120). Vaccine. 1989 Oct;7(5):465–473. doi: 10.1016/0264-410x(89)90164-3. [DOI] [PubMed] [Google Scholar]
  34. Robey W. G., Arthur L. O., Matthews T. J., Langlois A., Copeland T. D., Lerche N. W., Oroszlan S., Bolognesi D. P., Gilden R. V., Fischinger P. J. Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7023–7027. doi: 10.1073/pnas.83.18.7023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Sanchez-Pescador L., Burke R. L., Ott G., Van Nest G. The effect of adjuvants on the efficacy of a recombinant herpes simplex virus glycoprotein vaccine. J Immunol. 1988 Sep 1;141(5):1720–1727. [PubMed] [Google Scholar]
  37. Spire B., Sire J., Zachar V., Rey F., Barré-Sinoussi F., Galibert F., Hampe A., Chermann J. C. Nucleotide sequence of HIV1-NDK: a highly cytopathic strain of the human immunodeficiency virus. Gene. 1989 Sep 30;81(2):275–284. doi: 10.1016/0378-1119(89)90188-1. [DOI] [PubMed] [Google Scholar]
  38. Srinivasan A., Anand R., York D., Ranganathan P., Feorino P., Schochetman G., Curran J., Kalyanaraman V. S., Luciw P. A., Sanchez-Pescador R. Molecular characterization of human immunodeficiency virus from Zaire: nucleotide sequence analysis identifies conserved and variable domains in the envelope gene. Gene. 1987;52(1):71–82. doi: 10.1016/0378-1119(87)90396-9. [DOI] [PubMed] [Google Scholar]
  39. Steimer K. S., Haigwood N. L. Importance of conformation on the neutralizing antibody response to HIV-1 gp120. Biotechnol Ther. 1991;2(1-2):63–89. [PubMed] [Google Scholar]
  40. 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]
  41. Urlaub G., Chasin L. A. Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4216–4220. doi: 10.1073/pnas.77.7.4216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. 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]
  43. Zwart G., de Jong J. J., Wolfs T., van der Hoek L., Smit L., de Ronde A., Tersmette M., Nara P., Goudsmit J. Predominance of HIV-1 serotype distinct from LAV-1/HTLV-IIIB. Lancet. 1990 Feb 24;335(8687):474–474. doi: 10.1016/0140-6736(90)90707-c. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES