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@article{Viegas:2018:10.1371/journal.pone.0206838,
author = {Viegas, EO and Kroidl, A and Munseri, PJ and Missanga, M and Nilsson, C and Tembe, N and Bauer, A and Joachim, A and Joseph, S and Mann, P and Geldmacher, C and Fleck, S and Stohr, W and Scarlatti, G and Aboud, S and Bakari, M and Maboko, L and Hoelscher, M and Wahren, B and Robb, ML and Weber, J and McCormack, S and Biberfeld, G and Jani, I and Sandstrom, E and Lyamuya, E},
doi = {10.1371/journal.pone.0206838},
journal = {PLoS One},
pages = {1--19},
title = {Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design},
url = {http://dx.doi.org/10.1371/journal.pone.0206838},
volume = {13},
year = {2018}
}

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TY  - JOUR
AB  - BackgroundWe evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique.MethodsHealthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo.ResultsVaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p<0.001) and subtype C gp140 (24300 versus 2700, p<0.001) Env protein. At relatively low titers, neutralizing antibody responses using the TZM-bl assay were more frequent in vaccinees given adjuvanted protein boost.ConclusionIntradermal electroporation increased DNA-induced Gag response rates but did not show an impact on Env-specific responses nor on the magnitude of responses. Co-administration of HIV-MVA with rgp140/GLA-AF significa
AU  - Viegas,EO
AU  - Kroidl,A
AU  - Munseri,PJ
AU  - Missanga,M
AU  - Nilsson,C
AU  - Tembe,N
AU  - Bauer,A
AU  - Joachim,A
AU  - Joseph,S
AU  - Mann,P
AU  - Geldmacher,C
AU  - Fleck,S
AU  - Stohr,W
AU  - Scarlatti,G
AU  - Aboud,S
AU  - Bakari,M
AU  - Maboko,L
AU  - Hoelscher,M
AU  - Wahren,B
AU  - Robb,ML
AU  - Weber,J
AU  - McCormack,S
AU  - Biberfeld,G
AU  - Jani,I
AU  - Sandstrom,E
AU  - Lyamuya,E
DO  - 10.1371/journal.pone.0206838
EP  - 19
PY  - 2018///
SN  - 1932-6203
SP  - 1
TI  - Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design
T2  - PLoS One
UR  - http://dx.doi.org/10.1371/journal.pone.0206838
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000451763800018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206838
UR  - http://hdl.handle.net/10044/1/80744
VL  - 13
ER  -

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