First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090)

• Type of Material: Article
• Authors: Jonathan D. Fuchs, San Francisco Department of Public Health; Ian Frank, University of Pennsylvania; Marnie L. Elizaga, Fred Hutchinson Cancer Research Center; Mary Allen, National Institutes of Allergy and Infectious Diseases; Nicole Frahm, Fred Hutchinson Cancer Research Center; Nidhi Kochar, Fred Hutchinson Cancer Research Center; Sue Li, Fred Hutchinson Cancer Research Center; Srilatha Edupuganti, Emory University; Spyros A. Kalams, Vanderbilt University; Georgia D. Tomaras, Duke University; Rebecca Sheets, National Institutes of Allergy and Infectious Diseases; Michael Pensiero, National Institutes of Allergy and Infectious Diseases; Marc A. Tremblay, Profectus Biosciences, Inc.; Terry J. Higgins, Profectus Biosciences, Inc.; Theresa Latham, Profectus Biosciences, Inc.; Michael A. Egan, Profectus Biosciences, Inc.; David K. Clarke, Profectus Biosciences, Inc.; John H. Eldridge, Profectus Biosciences, Inc.; Mark Mulligan, Emory University; Nadine Rouphael, Emory University
• Language: English
• Date: 2015-06-05
• Publisher: Oxford University Press (OUP)
• Publication Version: Final Published Version
• Copyright Statement: © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/ofid/ofv082
• Title of Journal or Parent Work: Open Forum Infectious Diseases
• ISSN: 2328-8957
• Volume: 2
• Issue: 3
• Start Page: ofv082
• End Page: ofv082
• Grant/Funding Information: This work was also funded by the following grants: HHSN272200800061C; (Profectus); UM1 AI068614 (HVTN Core Fred Hutchinson Cancer Research Center); UM1 AI068635 (Statistical Center for HIV/AIDS Research and Prevention); UM1 AI068618; (HVTN Laboratory Program); UM1 AI069467; and P30 AI450008; (University of Pennsylvania); UM1 AI069418; (Emory); UM1 AI069439; (Vanderbilt); and UM1 AI069496 (San Francisco Department of Public Health).; HVTN 090 was conducted by the HIV Vaccine Trials Network (HVTN) and funded by the National Institutes of Allergy and Infectious Diseases.
• Keywords: T-CELL RESPONSES; NONHUMAN-PRIMATES; Science & Technology; GENE TRANSLOCATIONS; HIV vaccine; INFECTION; ATTENUATION; vesicular stomatitis virus; NEUROVIRULENCE; immunogenicity; dose-escalation; Life Sciences & Biomedicine; HIV-1 VACCINE; safety; TYPE-1; ANTIBODIES; VECTORS; Infectious Diseases
• Research Categories: Biology, Virology; Health Sciences, Public Health; Health Sciences, Immunology

Abstract

Background. We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods.  Sixty healthy, HIV-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation study. Groups of 12 participants received rVSV HIV-1 gag vaccine at 5 dose levels (4.6 × 10(3) to 3.4 × 10(7) particle forming units) (N = 10/group) or placebo (N = 2/group), delivered intramuscularly as bilateral injections at 0 and 2 months. Safety monitoring included VSV cultures from blood, urine, saliva, and swabs of oral lesions. Vesicular stomatitis virus-neutralizing antibodies, T-cell immunogenicity, and HIV-1 specific binding antibodies were assessed. Results.  Local and systemic reactogenicity symptoms were mild to moderate and increased with dose. No severe reactogenicity or product-related serious adverse events were reported, and all rVSV cultures were negative. All vaccine recipients became seropositive for VSV after 2 vaccinations. gag-specific T-cell responses were detected in 63% of participants by interferon-γ enzyme-linked immunospot at the highest dose post boost. Conclusions.  An attenuated replication-competent rVSV gag vaccine has an acceptable safety profile in healthy adults. This rVSV vector is a promising new vaccine platform for the development of vaccines to combat HIV-1 and other serious human diseases.