Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines

作者：Fatima Laher, Zoe Moodie, Kristen W. Cohen, Nicole Grunenberg, Linda‐Gail Bekker, Mary Allen, Nicole Frahm, Nicole L. Yates, Lynn Morris, Mookho Malahleha, Kathryn Mngadi, Brodie Daniels, Craig Innes, Kevin O. Saunders, Shannon Grant, Chenchen Yu, Peter B. Gilbert, Sanjay Phogat, Carlos A. DiazGranados, Marguerite Koutsoukos, Olivier Van Der Meeren, Carter Bentley, Nonhlanhla N. Mkhize, Michael Pensiero, Vijay Mehra, James G. Kublin, Lawrence Corey, David C. Montefiori, Glenda E. Gray, M. Juliana McElrath, Georgia D. Tomaras · 发表于：PLoS Medicine · 年份：2020 · DOI：10.1371/journal.pmed.1003038 · 被引用次数：48 · 研究领域：HIV Research and Treatment、Poxvirus research and outbreaks、vaccines and immunoinformatics approaches

BACKGROUND: HVTN 100 evaluated the safety and immunogenicity of an HIV subtype C pox-protein vaccine regimen, investigating a 12-month booster to extend vaccine-induced immune responses. METHODS AND FINDINGS: A phase 1-2 randomized double-blind placebo-controlled trial enrolled 252 participants (210 vaccine/42 placebo; median age 23 years; 43% female) between 9 February 2015 and 26 May 2015. Vaccine recipients received ALVAC-HIV (vCP2438) alone at months 0 and 1 and with bivalent subtype C gp120/MF59 at months 3, 6, and 12. Antibody (IgG, IgG3 binding, and neutralizing) and CD4+ T-cell (expressing interferon-gamma, interleukin-2, and CD40 ligand) responses were evaluated at month 6.5 for all participants and at months 12, 12.5, and 18 for a randomly selected subset. The primary analysis compared IgG binding antibody (bAb) responses and CD4+ T-cell responses to 3 vaccine-matched antigens at peak (month 6.5 versus 12.5) and durability (month 12 versus 18) timepoints; IgG responses to CaseA2_gp70_V1V2.B, a primary correlate of risk in RV144, were also compared at these same timepoints. Secondary and exploratory analyses compared IgG3 bAb responses, IgG bAb breadth scores, neutralizing antibody (nAb) responses, antibody-dependent cellular phagocytosis, CD4+ polyfunctionality responses, and CD4+ memory sub-population responses at the same timepoints. Vaccines were generally safe and well tolerated. During the study, there were 2 deaths (both in the vaccine group and both unrelated...