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

Publication ,  Journal Article
Cohen, KW; Fiore-Gartland, A; Walsh, SR; Yusim, K; Frahm, N; Elizaga, ML; Maenza, J; Scott, H; Mayer, KH; Goepfert, PA; Edupuganti, S ...
Published in: J Clin Invest
February 15, 2023

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.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

February 15, 2023

Volume

133

Issue

4

Location

United States

Related Subject Headings

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

Citation

APA
Chicago
ICMJE
MLA
NLM
Cohen, K. W., Fiore-Gartland, A., Walsh, S. R., Yusim, K., Frahm, N., Elizaga, M. L., … NIAID HVTN 106 Study Group. (2023). Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults. J Clin Invest, 133(4). https://doi.org/10.1172/JCI163338
Cohen, Kristen W., Andrew Fiore-Gartland, Stephen R. Walsh, Karina Yusim, Nicole Frahm, Marnie L. Elizaga, Janine Maenza, et al. “Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults.J Clin Invest 133, no. 4 (February 15, 2023). https://doi.org/10.1172/JCI163338.
Cohen KW, Fiore-Gartland A, Walsh SR, Yusim K, Frahm N, Elizaga ML, et al. Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults. J Clin Invest. 2023 Feb 15;133(4).
Cohen, Kristen W., et al. “Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults.J Clin Invest, vol. 133, no. 4, Feb. 2023. Pubmed, doi:10.1172/JCI163338.
Cohen KW, Fiore-Gartland A, Walsh SR, Yusim K, Frahm N, Elizaga ML, Maenza J, Scott H, Mayer KH, Goepfert PA, Edupuganti S, Pantaleo G, Hutter J, Morris DE, De Rosa SC, Geraghty DE, Robb ML, Michael NL, Fischer W, Giorgi EE, Malhi H, Pensiero MN, Ferrari G, Tomaras GD, Montefiori DC, Gilbert PB, McElrath MJ, Haynes BF, Korber BT, Baden LR, NIAID HVTN 106 Study Group. Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults. J Clin Invest. 2023 Feb 15;133(4).

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

February 15, 2023

Volume

133

Issue

4

Location

United States

Related Subject Headings

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