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DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial
Nadine G. Rouphael, … , Michael C. Keefer, the HVTN 105 Protocol Team and the NIAID HIV Vaccine Trials Network
Nadine G. Rouphael, … , Michael C. Keefer, the HVTN 105 Protocol Team and the NIAID HIV Vaccine Trials Network
Published September 30, 2019
Citation Information: J Clin Invest. 2019;129(11):4769-4785. https://doi.org/10.1172/JCI128699.
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Clinical Research and Public Health AIDS/HIV Article has an altmetric score of 30

DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial

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Abstract

BACKGROUND RV144 is the only preventive HIV vaccine regimen demonstrating efficacy in humans. Attempting to build upon RV144 immune responses, we conducted a phase 1, multicenter, randomized, double-blind trial to assess the safety and immunogenicity of regimens substituting the DNA-HIV-PT123 (DNA) vaccine for ALVAC-HIV in different sequences or combinations with AIDSVAX B/E (protein).METHODS One hundred and four HIV-uninfected participants were randomized to 4 treatment groups (T1, T2, T3, and T4) and received intramuscular injections at 0, 1, 3, and 6 months (M): T1 received protein at M0 and M1 and DNA at M3 and M6; T2 received DNA at M0 and M1 and protein at M3 and M6; T3 received DNA at M0, M1, M3, and M6 with protein coadministered at M3 and M6; and T4 received protein and DNA coadministered at each vaccination visit.RESULTS All regimens were well tolerated. Antibodies binding to gp120 and V1V2 scaffold were observed in 95%–100% of participants in T3 and T4, two weeks after final vaccination at high magnitude. While IgG3 responses were highest in T3, a lower IgA/IgG ratio was observed in T4. Binding antibodies persisted at 12 months in 35%–100% of participants. Antibody-dependent cell-mediated cytotoxicity and tier 1 neutralizing-antibody responses had higher response rates for T3 and T4, respectively. CD4+ T cell responses were detectable in all treatment groups (32%–64%) without appreciable CD8+ T cell responses.CONCLUSION The DNA/protein combination regimens induced high-magnitude and long-lasting HIV V1V2–binding antibody responses, and early coadministration of the 2 vaccines led to a more rapid induction of these potentially protective responses.TRIAL REGISTRATION ClinicalTrials.gov NCT02207920.FUNDING National Institute of Allergy and Infectious Diseases (NIAID) grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069511, UM1 AI069470, UM1 AI069534, P30 AI450008, UM1 AI069439, UM1 AI069481, and UM1 AI069496; the National Center for Advancing Translational Sciences, NIH (grant UL1TR001873); and the Bill & Melinda Gates Foundation (grant OPP52845).

Authors

Nadine G. Rouphael, Cecilia Morgan, Shuying S. Li, Ryan Jensen, Brittany Sanchez, Shelly Karuna, Edith Swann, Magdalena E. Sobieszczyk, Ian Frank, Gregory J. Wilson, Hong-Van Tieu, Janine Maenza, Aliza Norwood, James Kobie, Faruk Sinangil, Giuseppe Pantaleo, Song Ding, M. Juliana McElrath, Stephen C. De Rosa, David C. Montefiori, Guido Ferrari, Georgia D. Tomaras, Michael C. Keefer, the HVTN 105 Protocol Team and the NIAID HIV Vaccine Trials Network

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Figure 9

COMPASS CD4+ T cell polyfunctionality (PF) scores and mean probability of response heatmaps.

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COMPASS CD4+ T cell polyfunctionality (PF) scores and mean probability o...
The distribution and the box-and-whisker plot of PF scores for all vaccine-matched HIV Env peptide pools: ZM96 gp140-Env1, ZM96 gp140-Env2, and 92TH023-Env (A) and for ZM96 Gag peptide pool (C) by time point and treatment group (n = 25, 26, 25, 25 in T1–T4, respectively). The midline of the box-and-whisker plot denotes the median and the ends of the box-and-whisker plot denote the 25th and 75th percentiles. Bars and asterisks on top of box-and-whisker plots indicate the significant differences between treatment groups using Wilcoxon’s rank-sum test (*P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001) without multiple-comparisons adjustment. Heatmaps for CD4+ T cell response to any Env (B) and ZM96 Gag (D) show the mean posterior probabilities of antigen-specific responses from COMPASS. Columns correspond to the different subsets of cytokines being considered and rows correspond to mean across the individual participants in each treatment group at each time point. Each cell shows the probability that the corresponding antigen-specific subset (column) is being expressed in the corresponding treatment group in average (row), and is color coded ranging from white (zero) to dark purple (one).

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