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. 1994 Jan;93(1):140–146. doi: 10.1172/JCI116937

Effect of nonprotective vaccination on antibody response to subsequent human immunodeficiency virus infection.

S H Pincus 1, K G Messer 1, S L Hu 1
PMCID: PMC293746  PMID: 8282780

Abstract

We have investigated the systemic anti-HIV antibody response in chimpanzees who were immunized with live vaccinia containing either the HIV envelope glycoprotein (gp160IIIB) or a control antigen (herpes simplex virus glycoprotein D) and then challenged with either a high dose (300,000 TCID50) or low dose (100 TCID50) of HIVIIIB. HIV was subsequently isolated from all animals, indicating failure of the vaccination to protect against HIV infection. Serum antibody responses were evaluated before immunization, at the time of challenge with HIV, and at multiple time points in the 9 mo after challenge. Immunization resulted in a more rapid rise of antibody to gp160 in both high and low dose animals. Antibodies to the V3 loop induced upon infection were unaffected by immunization. In low dose animals, neutralizing antibody rose more rapidly and to higher levels in the immunized animals as compared with the control. There was no difference in neutralizing antibodies between immunized and control chimpanzees in the high dose group. Epitope mapping of the anti-gp 160 response indicated that immunization with gp160 vaccinia induced a postinfection antibody response to a region of gp41 (amino acids 718-743) that was not immunogenic in control-vaccinated animals. These data indicate that failed vaccination with the HIV envelope can alter both the timing and epitope specificity of the subsequent anti-HIV antibody response. These studies also define the evolution and fine specificity of the antibody response during the critical period immediately postinfection.

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Selected References

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  1. Adachi A., Gendelman H. E., Koenig S., Folks T., Willey R., Rabson A., Martin M. A. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol. 1986 Aug;59(2):284–291. doi: 10.1128/jvi.59.2.284-291.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Broliden P. A., von Gegerfelt A., Clapham P., Rosen J., Fenyö E. M., Wahren B., Broliden K. Identification of human neutralization-inducing regions of the human immunodeficiency virus type 1 envelope glycoproteins. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):461–465. doi: 10.1073/pnas.89.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chanh T. C., Dreesman G. R., Kanda P., Linette G. P., Sparrow J. T., Ho D. D., Kennedy R. C. Induction of anti-HIV neutralizing antibodies by synthetic peptides. EMBO J. 1986 Nov;5(11):3065–3071. doi: 10.1002/j.1460-2075.1986.tb04607.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chesebro B., Wehrly K. Development of a sensitive quantitative focal assay for human immunodeficiency virus infectivity. J Virol. 1988 Oct;62(10):3779–3788. doi: 10.1128/jvi.62.10.3779-3788.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chesebro B., Wehrly K., Metcalf J., Griffin D. E. Use of a new CD4-positive HeLa cell clone for direct quantitation of infectious human immunodeficiency virus from blood cells of AIDS patients. J Infect Dis. 1991 Jan;163(1):64–70. doi: 10.1093/infdis/163.1.64. [DOI] [PubMed] [Google Scholar]
  7. Cohen J. AIDS vaccine meeting: international trials soon. Science. 1991 Nov 1;254(5032):647–647. doi: 10.1126/science.1948042. [DOI] [PubMed] [Google Scholar]
  8. Cooney E. L., Collier A. C., Greenberg P. D., Coombs R. W., Zarling J., Arditti D. E., Hoffman M. C., Hu S. L., Corey L. Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein. Lancet. 1991 Mar 9;337(8741):567–572. doi: 10.1016/0140-6736(91)91636-9. [DOI] [PubMed] [Google Scholar]
  9. Dalgleish A. G., Chanh T. C., Kennedy R. C., Kanda P., Clapham P. R., Weiss R. A. Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide. Virology. 1988 Jul;165(1):209–215. doi: 10.1016/0042-6822(88)90674-5. [DOI] [PubMed] [Google Scholar]
  10. Dolin R., Graham B. S., Greenberg S. B., Tacket C. O., Belshe R. B., Midthun K., Clements M. L., Gorse G. J., Horgan B. W., Atmar R. L. The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials Network. Ann Intern Med. 1991 Jan 15;114(2):119–127. doi: 10.7326/0003-4819-114-2-119. [DOI] [PubMed] [Google Scholar]
  11. Evans D. J., McKeating J., Meredith J. M., Burke K. L., Katrak K., John A., Ferguson M., Minor P. D., Weiss R. A., Almond J. W. An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies. Nature. 1989 Jun 1;339(6223):385-8, 340. doi: 10.1038/339385a0. [DOI] [PubMed] [Google Scholar]
  12. Fast P. E., Walker M. C. Human trials of experimental AIDS vaccines. AIDS. 1993;7 (Suppl 1):S147–S159. [PubMed] [Google Scholar]
  13. Fultz P. N., Nara P., Barre-Sinoussi F., Chaput A., Greenberg M. L., Muchmore E., Kieny M. P., Girard M. Vaccine protection of chimpanzees against challenge with HIV-1-infected peripheral blood mononuclear cells. Science. 1992 Jun 19;256(5064):1687–1690. doi: 10.1126/science.256.5064.1687. [DOI] [PubMed] [Google Scholar]
  14. Geysen H. M., Rodda S. J., Mason T. J., Tribbick G., Schoofs P. G. Strategies for epitope analysis using peptide synthesis. J Immunol Methods. 1987 Sep 24;102(2):259–274. doi: 10.1016/0022-1759(87)90085-8. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Graham B. S., Belshe R. B., Clements M. L., Dolin R., Corey L., Wright P. F., Gorse G. J., Midthun K., Keefer M. C., Roberts N. J., Jr Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. The AIDS Vaccine Clinical Trials Network. J Infect Dis. 1992 Aug;166(2):244–252. doi: 10.1093/infdis/166.2.244. [DOI] [PubMed] [Google Scholar]
  17. Graham B. S., Matthews T. J., Belshe R. B., Clements M. L., Dolin R., Wright P. F., Gorse G. J., Schwartz D. H., Keefer M. C., Bolognesi D. P. Augmentation of human immunodeficiency virus type 1 neutralizing antibody by priming with gp160 recombinant vaccinia and boosting with rgp160 in vaccinia-naive adults. The NIAID AIDS Vaccine Clinical Trials Network. J Infect Dis. 1993 Mar;167(3):533–537. doi: 10.1093/infdis/167.3.533. [DOI] [PubMed] [Google Scholar]
  18. Hu S. L., Abrams K., Barber G. N., Moran P., Zarling J. M., Langlois A. J., Kuller L., Morton W. R., Benveniste R. E. Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160. Science. 1992 Jan 24;255(5043):456–459. doi: 10.1126/science.1531159. [DOI] [PubMed] [Google Scholar]
  19. Hu S. L., Fultz P. N., McClure H. M., Eichberg J. W., Thomas E. K., Zarling J., Singhal M. C., Kosowski S. G., Swenson R. B., Anderson D. C. Effect of immunization with a vaccinia-HIV env recombinant on HIV infection of chimpanzees. Nature. 1987 Aug 20;328(6132):721–723. doi: 10.1038/328721a0. [DOI] [PubMed] [Google Scholar]
  20. Hu S. L., Kosowski S. G., Dalrymple J. M. Expression of AIDS virus envelope gene in recombinant vaccinia viruses. Nature. 1986 Apr 10;320(6062):537–540. doi: 10.1038/320537a0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Kennedy R. C., Henkel R. D., Pauletti D., Allan J. S., Lee T. H., Essex M., Dreesman G. R. Antiserum to a synthetic peptide recognizes the HTLV-III envelope glycoprotein. Science. 1986 Mar 28;231(4745):1556–1559. doi: 10.1126/science.3006246. [DOI] [PubMed] [Google Scholar]
  23. Pincus S. H., Messer K. G., Schwartz D. H., Lewis G. K., Graham B. S., Blattner W. A., Fisher G. Differences in the antibody response to human immunodeficiency virus-1 envelope glycoprotein (gp160) in infected laboratory workers and vaccinees. J Clin Invest. 1993 May;91(5):1987–1996. doi: 10.1172/JCI116420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pincus S. H., Wehrly K., Chesebro B. Use of a focal infectivity assay for testing susceptibility of HIV to antiviral agents. Biotechniques. 1991 Mar;10(3):336–342. [PubMed] [Google Scholar]
  25. 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]
  26. Wintsch J., Chaignat C. L., Braun D. G., Jeannet M., Stalder H., Abrignani S., Montagna D., Clavijo F., Moret P., Dayer J. M. Safety and immunogenicity of a genetically engineered human immunodeficiency virus vaccine. J Infect Dis. 1991 Feb;163(2):219–225. doi: 10.1093/infdis/163.2.219. [DOI] [PubMed] [Google Scholar]
  27. 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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