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Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.

Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.
Author Information (click to view)

Churchyard G, Mlisana K, Karuna S, Williamson AL, Williamson C, Morris L, Tomaras GD, De Rosa SC, Gilbert PB, Gu N, Yu C, Mkhize NN, Hermanus T, Allen M, Pensiero M, Barnett SW, Gray G, Bekker LG, Montefiori DC, Kublin J, Corey L,


Churchyard G, Mlisana K, Karuna S, Williamson AL, Williamson C, Morris L, Tomaras GD, De Rosa SC, Gilbert PB, Gu N, Yu C, Mkhize NN, Hermanus T, Allen M, Pensiero M, Barnett SW, Gray G, Bekker LG, Montefiori DC, Kublin J, Corey L, (click to view)

Churchyard G, Mlisana K, Karuna S, Williamson AL, Williamson C, Morris L, Tomaras GD, De Rosa SC, Gilbert PB, Gu N, Yu C, Mkhize NN, Hermanus T, Allen M, Pensiero M, Barnett SW, Gray G, Bekker LG, Montefiori DC, Kublin J, Corey L,

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PloS one 2016 09 0111(9) e0161753 doi 10.1371/journal.pone.0161753

Abstract
BACKGROUND
The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa.

METHODS
Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo. Peak HIV specific humoral and cellular responses were measured.

RESULTS
184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years) and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens.

CONCLUSIONS
The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen.

TRIAL REGISTRATION
ClinicalTrials.gov NCT01418235.

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