PLoS Medicine (May 2020)

Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials.

  • Zoe Moodie,
  • Stephen R Walsh,
  • Fatima Laher,
  • Lucas Maganga,
  • Michael E Herce,
  • Sarita Naidoo,
  • Mina C Hosseinipour,
  • Craig Innes,
  • Linda-Gail Bekker,
  • Nicole Grunenberg,
  • Philipp Mann,
  • Chenchen Yu,
  • Allan C deCamp,
  • Maurine D Miner,
  • Nicole L Yates,
  • Jack Heptinstall,
  • Nonhlanhla N Mkhize,
  • One Dintwe,
  • Nicole Frahm,
  • Kristen W Cohen,
  • Mary Allen,
  • Julia Hutter,
  • Ralf Wagner,
  • Giuseppe Pantaleo,
  • M Juliana McElrath,
  • Georgia D Tomaras,
  • Lynn Morris,
  • David C Montefiori,
  • Erica Andersen-Nissen,
  • Glenda E Gray,
  • Peter B Gilbert,
  • James G Kublin,
  • NIAID HVTN 100 and HVTN 111 trial teams

DOI
https://doi.org/10.1371/journal.pmed.1003117
Journal volume & issue
Vol. 17, no. 5
p. e1003117

Abstract

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BackgroundDNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with harmonized trial designs. HIV Vaccine Trials Network (HVTN) 111 tested DNA plasmid prime by needle or needleless injection device (Biojector) and DNA plasmid plus gp120 protein plus MF59 adjuvant boost. HVTN 100 tested ALVAC prime and ALVAC plus gp120 protein plus MF59 adjuvant boost (same protein/adjuvant as HVTN 111) by needle.Methods and findingsThe primary endpoints for this analysis were binding antibody (bAb) responses to HIV antigens (gp120 from strains ZM96, 1086, and TV1; variable 1 and 2 [V1V2] regions of gp120 from strains TV1, 1086, and B.CaseA, as 1086 V1V2 and B.CaseA were correlates of risk in the RV144 efficacy trial), neutralizing antibody (nAb) responses to pseudoviruses TV1c8.2 and MW925.26, and cellular responses to vaccine-matched antigens (envelope [Env] from strains ZM96, 1086, and TV1; and Gag from strains LAI and ZM96) at month 6.5, two weeks after the fourth vaccination. Per-protocol cohorts included vaccine recipients from HVTN 100 (n = 186, 60% male, median age 23 years) enrolled between February 9, 2015, and May 26, 2015 and from HVTN 111 (n = 56, 48% male, median age 24 years) enrolled between June 21, 2016, and July 13, 2017. IgG bAb response rates were 100% to 3 Env gp120 antigens in both trials. Response rates to V1V2 were lower and similar in both trials except to vaccine-matched 1086 V1V2, with rates significantly higher for the DNA-primed regimen than the ALVAC-primed regimen: 96.6% versus 72.7% (difference = 23.9%, 95% CI 15.6%-32.2%, p 98% in both trials, with significantly higher 50% inhibitory dilution (ID50) among DNA-primed positive responders (n = 53) versus ALVAC-primed (n = 182) to tier 1A MW965.26 (GM 577.7 versus 265.7, ratio = 2.17, 95% CI 1.67-2.83, p ConclusionsIn this study, we found that further investigation of DNA/protein regimens is warranted given enhanced immunogenicity to the V1V2 correlates of decreased HIV-1 acquisition risk identified in RV144, the only HIV vaccine trial to date to show any efficacy.