Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.

• Type of Material: Article
• Authors: Jonathan D Fuchs, San Francisco Department of Public Health; Pierre-Alexandre Bart, Centre Hospitalier Universitaire Vaudois; Nicole Frahm, Fred Hutchinson Cancer Research Center; Cecilia Morgan, Fred Hutchinson Cancer Research Center; Peter B Gilbert, Fred Hutchinson Cancer Research Center; Nidhi Kochar, Fred Hutchinson Cancer Research Center; Stephen C DeRosa, Fred Hutchinson Cancer Research Center; Georgia D Tomaras, Duke University; Theresa M Wagner, San Francisco Department of Public Health; Lindsey R Baden, Brigham and Women's Hospital; Beryl A Koblin, New York Blood Center; Nadine Rouphael, Emory University; Spyros A Kalams, Vanderbilt University; Michael C Keefer, University of Rochester; Paul A Goepfert, University of Alabama at Birmingham; Magdalena E Sobieszczyk, Columbia University; Kenneth H Mayer, Harvard University; Edith Swann, National Institute of Allergy and Infectious Diseases; Hua-Xin Liao, Duke University; Barton F Haynes, Duke University; Barney S Graham, National Institute of Allergy and Infectious Diseases; M Juliana McElrath, Fred Hutchinson Cancer Research Center; HIV/AIDS Clinical Trials Network, National Institute of Allergy and Infectious Diseases
• Language: English
• Date: 2015-05-23
• Publisher: OMICS International
• Publication Version: Final Published Version
• Copyright Statement: ©2015 Fuchs JD, et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.4172/2155-6113.1000461
• Title of Journal or Parent Work: Journal of AIDS and Clinical Research
• ISSN: 2155-6113
• Volume: 6
• Issue: 5
• Start Page: 461
• Grant/Funding Information: This work was also supported by the following grants: UM1 AI068614 (HVTN Core FHCRC), UM1 AI068635 (SCHARP), UM1 AI068618 (HVTN Laboratory Program), UM1 AI069452 (UAB), UM1AI069418 (Emory), UM1AI069511 (Rochester), UM1 AI069412 (BWH and Fenway), UM1 AI069470 (NY Blood Center –Bronx, NY Blood Center –Union Square and Columbia University), UM1 AI069439 (Vanderbilt), UM1 AI069496 (SFDPH), and UM1 AI069481 (Seattle); HVTN 077 was conducted by the HIV Vaccine Trials Network (HVTN) and supported by the National Institutes of Allergy and Infectious Diseases (NIAID-NIH).
• Keywords: Adenovirus 35; Adenovirus 5; DNA vaccine; Randomized clinical trial; HIV Vaccine
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Epidemiology; Health Sciences, Immunology

Abstract

BACKGROUND: Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. METHODS: HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. RESULTS: All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. CONCLUSIONS: Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted.