Volume 9 Supplement 2
Antibody-mediated inhibition of HIV-1 elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults
© Joachim et al; licensee BioMed Central Ltd. 2012
Published: 13 September 2012
We evaluated HIV antibody (Ab) responses elicited by immunization, in a phase I/II placebo-controlled double blind trial using multiclade, multigene HIV-1-DNA prime boosted with HIV-MVA conducted among healthy volunteers in Tanzania (HIVIS03).
Sixty HIV-uninfected volunteers, randomized into groups of 20 received placebo or 1 mg HIV-DNA intradermally (id) or 3.8 mg intramuscularly (im). DNA plasmids containing HIV-1 gp160 subtypes A, B, C; rev B; p17/p24 gag A, B and RTmut B were given at months 0, 1 and 3 using a needle-free Biojector device. HIV-MVA expressing CRF01_AE HIV-1 env, gag, pol was administered im by needle at months 9 and 21. Sera were tested at baseline, two months post-first and four weeks post-second HIV-MVA boosting. HIV Ab responses were tested using pseudoviruses and TZM-bl cells as well as luciferase-expressing infectious molecular clones (IMC-LucR) in PBMC-based assays. ADCC responses were tested using the flow cytometry GranToxiLux-based assay.
Neutralizing Ab activity was demonstrated only in the PBMC assay, and after the second MVA boost in 24 (83%) of 29 vaccinees against the clade CRF01_AE CM235 IMC and in 21 (72%) of 29 vaccinees against clade B SF162-IMC. NK cell depletion from PBMC targets resulted in a significant loss of HIV inhibition by vaccinee sera, indicating a role of Ab-mediated Fcγ-receptor function. Vaccine-induced ADCC responses were detected in 21 (75%) of 28 vaccinees after the second HIV-MVA boost. ADCC Ab titers did not differ significantly between id- (median 840, range 300-5400) and im-primed (median 880, range 400-3600) vaccinees (p=0.45).
HIV-DNA priming followed by two HIV-MVA boosts elicited HIV-specific inhibitory and/or ADCC-mediating antibody responses in a high proportion of Tanzanian adults.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.