• Lindsey R Baden, Etienne Karita, Gaudensia Mutua, Linda-Gail Bekker, Glenda Gray, Liesl Page-Shipp, Stephen R Walsh, Julien Nyombayire, Omu Anzala, Surita Roux, Fatima Laher, Craig Innes, Michael S Seaman, Yehuda Z Cohen, Lauren Peter, Nicole Frahm, M Juliana McElrath, Peter Hayes, Edith Swann, Nicole Grunenberg, Maria Grazia-Pau, Mo Weijtens, Jerry Sadoff, Len Dally, Angela Lombardo, Jill Gilmour, Josephine Cox, Raphael Dolin, Patricia Fast, Dan H Barouch, Dagna S Laufer, and B003-IPCAVD004-HVTN091 Study Group.
• Ann. Intern. Med. 2016 Mar 1; 164 (5): 313-22.

BackgroundA prophylactic HIV-1 vaccine is a global health priority.ObjectiveTo assess a novel vaccine platform as a prophylactic HIV-1 regimen.DesignRandomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149).SettingUnited States, East Africa, and South Africa.PatientsHealthy adults without HIV infection.Intervention2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations.MeasurementsSafety and immunogenicity and the effect of baseline vector immunity.Results217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States.LimitationsBecause the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown.ConclusionBoth vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response.Primary Funding SourceInternational AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland.

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