Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers.
BACKGROUND: Use of the recombinant proteins NefTat and gp120(W61D) 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-1(W61D) 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.
Goepfert, PA; Tomaras, GD; Horton, H; Montefiori, D; Ferrari, G; Deers, M; Voss, G; Koutsoukos, M; Pedneault, L; Vandepapeliere, P; McElrath, MJ; Spearman, P; Fuchs, JD; Koblin, BA; Blattner, WA; Frey, S; Baden, LR; Harro, C; Evans, T; NIAID HIV Vaccine Trials Network,
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