Annals of Internal Medicine
1 March 2016, Vol. 164. No. 5
http://annals.org/issue.aspx

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Original Research
Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV-1 Prevention: A Randomized Trial
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Lindsey R. Baden, MD; Etienne Karita, MD; Gaudensia Mutua, MBChB; Linda-Gail Bekker, MD; Glenda Gray, MBBCh; Liesl Page-Shipp, MD; Stephen R. Walsh, MD; Julien Nyombayire, MD; Omu Anzala, MBChB, PhD; Surita Roux, MD; Fatima Laher, MBBCh; Craig Innes, MD; Michael S. Seaman, PhD; Yehuda Z. Cohen, MD; Lauren Peter; Nicole Frahm, PhD; M. Juliana McElrath, MD, PhD; Peter Hayes, PhD; Edith Swann, PhD; Nicole Grunenberg, MD; Maria Grazia-Pau, MSc; Mo Weijtens, PhD; Jerry Sadoff, MD; Len Dally, MSc; Angela Lombardo, PhD; Jill Gilmour, PhD; Josephine Cox, PhD; Raphael Dolin, MD; Patricia Fast, MD, PhD; Dan H. Barouch, MD, PhD; Dagna S. Laufer, MD, for the B003-IPCAVD004-HVTN091 Study Group
Abstract
Background: A prophylactic HIV-1 vaccine is a global health priority.
Objective: To assess a novel vaccine platform as a prophylactic HIV-1 regimen.
Design: Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149)
Setting: United States, East Africa, and South Africa.
Patients: Healthy adults without HIV infection.
Intervention: 2 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.
Measurements: Safety and immunogenicity and the effect of baseline vector immunity.
Results: 217 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.
Limitations: Because 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.
Conclusion: Both 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 Source: International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland.

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Ideas and Opinions
Interrupting Ebola Transmission in Liberia Through Community-Based Initiatives
Mosoka Fallah, PhD, MPH; Bernice Dahn, MD, MPH; Tolbert G. Nyenswah, Esq, MPH; Moses Massaquoi, MD, MPH; Laura A. Skrip, MPH; Dan Yamin, PhD; Martial Ndeffo Mbah, PhD; Netty Joe, MD; Siedoh Freeman, MD; Thomas Harris, BA; Zinnah Benson, BBA; and Alison P. Galvani, PhD
In Liberia, programs based on community engagement were effective in controlling the Ebola virus disease epidemic. This article details the community-based initiative that was instrumental to the shift in transmission dynamics.