Intramuscular and Intradermal Electroporation of HIV-1 PENNVAX-GP(R) DNA Vaccine and IL-12 Is Safe, Tolerable, Acceptable in Healthy Adults

• Type of Material: Article
• Authors: Srilatha Edupuganti, Emory University; Stephen C. De Rosa, Fred Hutchinson Cancer Research Center; Marnie Elizaga, Fred Hutchinson Cancer Research Center; Yiwen Lu, Fred Hutchinson Cancer Research Center; Xue Han, Fred Hutchinson Cancer Research Center; Yunda Huang, Fred Hutchinson Cancer Research Center; Edith Swann, National Institutes of Health; Laura Polakowski, National Institutes of Health; Spyros A. Kalams, Vanderbilt University; Michael Keefer, University of Rochester; Janine Maenza, 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.; Niranjan Y. Sardesai, Inovio Pharmaceuticals Inc.; Mark L. Bagarazzi, Inovio Pharmaceuticals Inc.; Peter B. Gilbert, Fred Hutchinson Cancer Research Center; James G. Kublin, Fred Hutchinson Cancer Research Center; Lawrence Corey, Fred Hutchinson Cancer Research Center; David B. Weiner, Wistar Institute
• Language: English
• Date: 2020-12-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/vaccines8040741
• Title of Journal or Parent Work: VACCINES
• Volume: 8
• Issue: 4
• Start Page: 1
• End Page: 15
• Grant/Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID, https://www.niaid.nih.gov/) U.S. Public Health Service Grants UM1 AI068614 (LOC: HIV Vaccine Trials Network), UM1 AI068635 (SDMC: HIV Vaccine Trials Network), UM1 AI068618 (LC: HIV Vaccine Trials Network), U01 AI069418-08 (Emory-CDC Clinical Trials Unit), UM1 AI069511 (University of Rochester HIV/AIDS Clinical Trials Unit), UM1 AI069439 (Vanderbilt Clinical Trial Unit), UM1 AI069481 (Seattle-Lausanne-Kampala Clinical Trials Unit) and HVDDT Contract HHSN2722008000063C (Inovio Pharmaceuticals). This work was also supported, in part, by IPCAVD Award U19 AI09646-03 (DBW). The opinions expressed in this article are those of the authors and do not necessarily represent the official views of the NIAID or the National Institutes of Health (NIH).
• Keywords: PARAMETERS; intradermal; intramuscular; electroporation; Research & Experimental Medicine; Science & Technology; DNA vaccine; safety; Life Sciences & Biomedicine; HIV vaccine; Immunology; IMMUNOGENICITY; Medicine, Research & Experimental; IL-12; DELIVERY
• Research Categories: Biology, Virology; Health Sciences, Immunology

Abstract

Background: Several techniques are under investigation to improve the immunogenicity of HIV-1DNAvaccine candidates. DNAvaccines are advantageous due to their ease of design, expression of multiple antigens, and safety. Methods: The HVTN 098 trial assessed the PENNVAX®-GP DNA vaccine (encoding HIV env, gag, pol) administered with or without plasmid IL-12 at 0-, 1-, 3-, and 6-month timepoints via intradermal (ID) or intramuscular (IM) electroporation (EP) in healthy, adult participants. We report on safety, tolerability, and acceptability. Results: HVTN 098 enrolled 94 participants: 85 received PENNVAX®-GP and nine received placebo. Visual analog scale (VAS) pain scores immediately after each vaccination were lower in the ID/EP than in the IM/EP group (medians 4.1–4.6 vs. 6–6.5, p < 0.01). IM/EP participants reported greater pain and/or tenderness at the injection site. Most ID/EP participants had skin lesions such as scabs/eschars, scars, and pigmentation changes, which resolved within 6 months in 51% of participants (24/55). Eighty-two percent of IM/EP and 92% of ID/EP participant survey responses showed acceptable levels of discomfort.