Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers

Paul A. Goepfert, Georgia D. Tomaras, Helen Horton, David Montefiori, Guido Ferrari, Mark Deers, Gerald Voss, Marguerite Koutsoukos, Louise Pedneault, Pierre Vandepapeliere, M. Juliana McElrath, Paul Spearman, Jonathan D. Fuchs, Beryl A. Koblin, William A. Blattner, Sharon Frey, Lindsey R. Baden, Clayton Harro, Thomas Evans

Research output: Contribution to journalArticle

Abstract

Background: Use of the recombinant proteins NefTat and gp120W61D formulated with the AS02A adjuvant system was previously shown to protect against AIDS in a rhesus macaque SHIV animal model system. Methods: Eighty-four HIV uninfected human participants were vaccinated intramuscularly at 0, 1, and 3 months and evaluated for safety. Immune responses were analyzed for the presence of vaccine-induced antibody and T lymphocyte responses. Results: The vaccines were safe and well tolerated at all doses. Nef-, Tat-, and gp120-specific binding antibodies were induced in all individuals that received the respective antigen, lasting up to 9 months after the final immunization. Antibodies able to neutralize the T-cell laboratory-adapted strain of HIV-1W61D were detected in the majority of vacinees, but did not neutralize primary isolates. Envelope-specific antibody-dependent cell cytoxicity was detected in most of the individuals receiving gp120. Robust and persistent HIV-specific lymphoproliferative responses were detected against all subunit proteins in the majority of immunized participants. As expected, HIV-specific CD8 T-cell responses were not detected. Conclusions: Despite the lack of primary isolate neutralizing antibody induction, the observed high frequency and magnitude of other immune responses warrant further work with this vaccine or vaccine components.

Original languageEnglish (US)
Pages (from-to)510-518
Number of pages9
JournalVaccine
Volume25
Issue number3
DOIs
StatePublished - Jan 5 2007

Keywords

  • AS02A adjuvant
  • Clinical trial
  • HIV vaccine
  • Nef
  • Tat
  • gp120

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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  • Cite this

    Goepfert, P. A., Tomaras, G. D., Horton, H., Montefiori, D., Ferrari, G., Deers, M., Voss, G., Koutsoukos, M., Pedneault, L., Vandepapeliere, P., McElrath, M. J., Spearman, P., Fuchs, J. D., Koblin, B. A., Blattner, W. A., Frey, S., Baden, L. R., Harro, C., & Evans, T. (2007). Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers. Vaccine, 25(3), 510-518. https://doi.org/10.1016/j.vaccine.2006.07.050