Subtype C ALVAC-HIV and bivalent subtype C gp120/MF59 HIV-1 vaccine in low-risk, HIV-uninfected, South African adults: a phase 1/2 trial

作者：Linda‐Gail Bekker, Zoe Moodie, Nicole Grunenberg, Fatima Laher, Georgia D. Tomaras, Kristen W. Cohen, Mary Allen, Mookho Malahleha, Kathryn Mngadi, Brodie Daniels, Craig Innes, Carter Bentley, Nicole Frahm, Daryl E. Morris, Lynn Morris, Nonhlanhla N. Mkhize, David C. Montefiori, Marcella Sarzotti‐Kelsoe, Shannon Grant, Chenchen Yu, Vijay Mehra, Michael Pensiero, Sanjay Phogat, Carlos A. DiazGranados, Susan W. Barnett, Niranjan Kanesa-thasan, Marguerite Koutsoukos, Nelson L. Michael, Merlin L. Robb, James G. Kublin, Peter B. Gilbert, Lawrence Corey, Glenda Gray, M. Juliana McElrath · 发表于：The Lancet HIV · 年份：2018 · DOI：10.1016/s2352-3018(18)30071-7 · 被引用次数：125 · 研究领域：HIV Research and Treatment、Poxvirus research and outbreaks、Immunotherapy and Immune Responses

BACKGROUND: Modest efficacy was reported for the HIV vaccine tested in the RV144 trial, which comprised a canarypox vector (ALVAC) and envelope (env) glycoprotein (gp120). These vaccine components were adapted to express HIV-1 antigens from strains circulating in South Africa, and the adjuvant was changed to increase immunogenicity. Furthermore, 12-month immunisation was added to improve durability. In the HIV Vaccine Trials Network (HVTN) 100 trial, we aimed to assess this new regionally adapted regimen for advancement to efficacy testing. METHODS: HVTN 100 is a phase 1/2, randomised controlled, double-blind trial at six community research sites in South Africa. We randomly allocated adults (aged 18-40 years) without HIV infection and at low risk of HIV infection to either the vaccine regimen (intramuscular injection of ALVAC-HIV vector [vCP2438] at 0, 1, 3, 6, and 12 months plus bivalent subtype C gp120 and MF59 adjuvant at 3, 6, and 12 months) or placebo, in a 5:1 ratio. Randomisation was done by computer-generated list. Participants, investigators, and those assessing outcomes were masked to random assignments. Primary outcomes included safety and immune responses associated with correlates of HIV risk in RV144, 2 weeks after vaccination at 6 months (month 6·5). We compared per-protocol participants (ie, those who completed the first four vaccinations and provided samples at month 6·5) from HVTN 100 with stored RV144 samples assayed contemporaneously. This trial is regist...