Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults.

Abstract

BACKGROUNDMosaic and consensus HIV-1 immunogens provide two distinct approaches to elicit greater breadth of coverage against globally circulating HIV-1 and have shown improved immunologic breadth in nonhuman primate models.METHODSThis double-blind randomized trial enrolled 105 healthy HIV-uninfected adults who received 3 doses of either a trivalent global mosaic, a group M consensus (CON-S), or a natural clade B (Nat-B) gp160 env DNA vaccine followed by 2 doses of a heterologous modified vaccinia Ankara-vectored HIV-1 vaccine or placebo. We performed prespecified blinded immunogenicity analyses at day 70 and day 238 after the first immunization. T cell responses to vaccine antigens and 5 heterologous Env variants were fully mapped.RESULTSEnv-specific CD4+ T cell responses were induced in 71% of the mosaic vaccine recipients versus 48% of the CON-S recipients and 48% of the natural Env recipients. The mean number of T cell epitopes recognized was 2.5 (95% CI, 1.2-4.2) for mosaic recipients, 1.6 (95% CI, 0.82-2.6) for CON-S recipients, and 1.1 (95% CI, 0.62-1.71) for Nat-B recipients. Mean breadth was significantly greater in the mosaic group than in the Nat-B group using overall (P = 0.014), prime-matched (P = 0.002), heterologous (P = 0.046), and boost-matched (P = 0.009) measures. Overall T cell breadth was largely due to Env-specific CD4+ T cell responses.CONCLUSIONPriming with a mosaic antigen significantly increased the number of epitopes recognized by Env-specific T cells and enabled more, albeit still limited, cross-recognition of heterologous variants. Mosaic and consensus immunogens are promising approaches to address global diversity of HIV-1.TRIAL REGISTRATIONClinicalTrials.gov NCT02296541.FUNDINGUS NIH grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069412, UL1 RR025758, P30 AI064518, UM1 AI100645, and UM1 AI144371, and Bill & Melinda Gates Foundation grant OPP52282.

• Authors: Kristen W Cohen, Andrew Fiore-Gartland, Stephen R Walsh, Karina Yusim, Nicole Frahm, Marnie L Elizaga, Janine Maenza, Hyman Scott, Kenneth H Mayer, Paul A Goepfert, Srilatha Edupuganti, Giuseppe Pantaleo, Julia Hutter, Daryl E Morris, Stephen C De Rosa, Daniel E Geraghty, Merlin L Robb, Nelson L Michael, Will Fischer, Elena E Giorgi, Harman Malhi, Michael N Pensiero, Guido Ferrari, Georgia D Tomaras, David C Montefiori, Peter B Gilbert, M Juliana McElrath, Barton F Haynes, Bette T Korber, Lindsey R Baden, NIAID HVTN 106 Study Group
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 133 Issue 4 (02 15 2023) ISSN: 1558-8238 [Electronic] United States
• PMID: 36787249 (Publication Type: Randomized Controlled Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• AIDS Vaccines
• HIV Antibodies
• Vaccines, DNA

Topics

• Animals
• Consensus
• Immunity, Cellular
• Vaccination
• Vaccinia virus
• HIV Infections
• AIDS Vaccines
• HIV Antibodies
• Vaccines, DNA