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

Publication ,  Journal Article
Moodie, Z; Walsh, SR; Laher, F; Maganga, L; Herce, ME; Naidoo, S; Hosseinipour, MC; Innes, C; Bekker, L-G; Grunenberg, N; Mann, P; Yu, C ...
Published in: PLoS Med
May 2020

BACKGROUND: DNA 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 FINDINGS: The 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 < 0.001). Among positive responders, bAb net mean fluorescence intensity (MFI) was significantly higher with the DNA-primed regimen than ALVAC-primed for 1086 V1V2 (geometric mean [GM] 2,833.3 versus 1,200.9; ratio = 2.36, 95% CI 1.42-3.92, p < 0.001) and B.CaseA V1V2 (GM 2314.0 versus 744.6, ratio = 3.11, 95% CI 1.51-6.38, p = 0.002). nAb response rates were >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 < 0.001) and to TV1c8.2 (GM 187.3 versus 100.4, ratio = 1.87, 95% CI 1.48-2.35, p < 0.001). CD4+ T-cell response rates were significantly higher with DNA plasmid prime via Biojector than ALVAC prime (91.4% versus 52.8%, difference = 38.6%, 95% CI 20.5%-56.6%, p < 0.001 for ZM96.C; 88.0% versus 43.1%, difference = 44.9%, 95% CI 26.7%-63.1%, p < 0.001 for 1086.C; 55.5% versus 2.2%, difference = 53.3%, 95% CI 23.9%-82.7%, p < 0.001 for Gag LAI/ZM96). The study's main limitations include the nonrandomized comparison of vaccines from 2 different trials, the lack of data on immune responses to other non-vaccine-matched antigens, and the uncertain clinical significance of the observed immunological effects. CONCLUSIONS: In 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.

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Published In

PLoS Med

DOI

EISSN

1549-1676

Publication Date

May 2020

Volume

17

Issue

5

Start / End Page

e1003117

Location

United States

Related Subject Headings

  • Young Adult
  • Vaccination
  • Plasmids
  • Male
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antigens
  • HIV Antibodies
  • Genetic Vectors
 

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Moodie, Z., Walsh, S. R., Laher, F., Maganga, L., Herce, M. E., Naidoo, S., … NIAID HVTN 100 and HVTN 111 trial teams. (2020). Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials. PLoS Med, 17(5), e1003117. https://doi.org/10.1371/journal.pmed.1003117
Moodie, Zoe, Stephen R. Walsh, Fatima Laher, Lucas Maganga, Michael E. Herce, Sarita Naidoo, Mina C. Hosseinipour, et al. “Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials.PLoS Med 17, no. 5 (May 2020): e1003117. https://doi.org/10.1371/journal.pmed.1003117.
Moodie Z, Walsh SR, Laher F, Maganga L, Herce ME, Naidoo S, et al. Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials. PLoS Med. 2020 May;17(5):e1003117.
Moodie, Zoe, et al. “Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials.PLoS Med, vol. 17, no. 5, May 2020, p. e1003117. Pubmed, doi:10.1371/journal.pmed.1003117.
Moodie Z, Walsh SR, Laher F, Maganga L, Herce ME, Naidoo S, Hosseinipour MC, Innes C, Bekker L-G, Grunenberg N, Mann P, Yu C, deCamp AC, Miner MD, Yates NL, Heptinstall J, Mkhize NN, Dintwe O, Frahm N, Cohen KW, Allen M, Hutter J, Wagner R, Pantaleo G, McElrath MJ, Tomaras GD, Morris L, Montefiori DC, Andersen-Nissen E, Gray GE, Gilbert PB, Kublin JG, NIAID HVTN 100 and HVTN 111 trial teams. Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials. PLoS Med. 2020 May;17(5):e1003117.

Published In

PLoS Med

DOI

EISSN

1549-1676

Publication Date

May 2020

Volume

17

Issue

5

Start / End Page

e1003117

Location

United States

Related Subject Headings

  • Young Adult
  • Vaccination
  • Plasmids
  • Male
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antigens
  • HIV Antibodies
  • Genetic Vectors