Robust antibody and cellular responses induced by DNA-only vaccination for HIV

• Type of Material: Article
• Authors: Stephen C. De Rosa, Fred Hutchinson Cancer Research Center; Srilatha Edupuganti, Emory University; Yunda Huang, Fred Hutchinson Cancer Research Center; Xue Han, Fred Hutchinson Cancer Research Center; Marnie Elizaga, Fred Hutchinson Cancer Research Center; Edith Swann, NIH; Laura Polakowski, NIH; Spyros A. Kalams, Vanderbilt University; Michael S. Keefer, University of Rochester; Janine Maenza, Fred Hutchinson Cancer Research Center; Yiwen Lu, Fred Hutchinson Cancer Research Center; Megan C. Wise, Inovio Pharmaceuticals Inc.; Jian Yan, Inovio Pharmaceuticals Inc.; Matthew P. Morrow, Inovio Pharmaceuticals Inc.; Amir S. Khan, Inovio Pharmaceuticals Inc.; Jean D. Boyer, Inovio Pharmaceuticals Inc.; Laurent Humeau, Inovio Pharmaceuticals Inc.; Scott White, Inovio Pharmaceuticals Inc.; Michael Pensiero, NIH; Niranjan Y. Sardesai, Inovio Pharmaceuticals Inc.; Mark L. Bagarazzi, Inovio Pharmaceuticals Inc.; David B. Weiner, Wistar Institute; Guido Ferrari, Duke University; Georgia D. Tomaras, Duke University; David C. Montefiori, Duke University; Lawrence Corey, Fred Hutchinson Cancer Research Center; M. Juliana McElrath, Fred Hutchinson Cancer Research Center
• Language: English
• Date: 2020-07-09
• Publisher: The American Society for Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2020, American Society for Clinical Investigation.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1172/jci.insight.137079
• Title of Journal or Parent Work: JCI Insight
• Volume: 5
• Issue: 13
• Grant/Funding Information: U.S. Public Health Service Grants UM1 AI068618 (to Laboratory Center: HVTN), UM1 AI068614 (to Leadership and Operations Center: HVTN), UM1 AI068635 (to Statistical and Data Monitoring Center: HVTN),; HIV Vaccine Design and Development Team Contract HHSN2722008000063C (to Inovio Pharmaceuticals).; This work was supported by National Institute of Allergy and Infectious Diseases (NIAID), U.S. Public Health Service grants, an HIV Vaccine Design and Development Team contract, Integrated Preclinical/Clinical AIDS Vaccine Development Program, and an NIH award.; This work was also supported, in part, by Integrated Preclinical/Clinical AIDS Vaccine Development Program award U19 AI09646-03 (to DBW) and NIH award P01 AI120756 (to GDT).; U01 AI069418-08 (to Emory-CDC Clinical Trials Unit), UM1 AI069511 (to University of Rochester HIV/AIDS Clinical Trials Unit), UM1 AI069439 (to Vanderbilt Clinical Trial Unit), UM1 AI069481 (to Seattle-Lausanne Clinical Trials Unit)
• Keywords: Delivery; T-cells; Binding; Aidsvax; Immunogenicity; Immune responses; Memory; Vaccines; Medicine, Research & Experimental; Electroporation; Efficacy; Research & Experimental Medicine; Life Sciences & Biomedicine; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Public Health; Health Sciences, Immunology; Biology, Cell

Abstract

BACKGROUND HVTN 098, a randomized, double-blind, placebo-controlled trial, evaluated the safety, tolerability, and immunogenicity of PENNVAX-GP HIV DNA vaccine, administered with or without plasmid IL-12 (pIL-12), via intradermal (ID) or intramuscular (IM) electroporation (EP) in healthy, HIV-uninfected adults. The study tested whether PENNVAX-GP delivered via ID/EP at one-fifth the dose could elicit equivalent immune responses to delivery via IM/EP and whether inclusion of pIL-12 provided additional benefit. METHODS Participants received DNA encoding HIV-1 env/gag/pol in 3 groups: 1.6 mg ID (ID no IL-12 group, n = 20), 1.6 mg ID + 0.4 mg pIL-12 (ID + IL-12 group, n = 30), 8 mg IM + 1 mg pIL-12 (IM + IL-12 group, n = 30), or placebo (n = 9) via EP at 0, 1, 3, and 6 months. Results of cellular and humoral immunogenicity assessments are reported. RESULTS Following vaccination, the frequency of responders (response rate) to any HIV protein based on CD4+ T cells expressing IFN-γ or IL-2 was 96% for both the ID + IL-12 and IM + IL-12 groups; CD8+ T cell response rates were 64% and 44%, respectively. For ID delivery, the inclusion of pIL-12 increased CD4+ T cell response rate from 56% to 96%. The frequency of responders was similar (≥90%) for IgG binding antibody to gp140 consensus Env across all groups, but the magnitude was higher in the ID + IL-12 group compared with the IM + IL-12 group. CONCLUSION PENNVAX-GP DNA induced robust cellular and humoral immune responses, demonstrating that immunogenicity of DNA vaccines can be enhanced by EP route and inclusion of pIL-12. ID/EP was dose sparing, inducing equivalent, or in some aspects superior, immune responses compared with IM/EP.