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Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals | Abstract
ISSN 2155-6113

Journal of AIDS & Clinical Research
Open Access

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Research Article

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

Jonathan D Fuchs1,2,*, Pierre-Alexandre Bart3, Nicole Frahm4, Cecilia Morgan4, Peter B Gilbert4, Nidhi Kochar4, Stephen C DeRosa4, Georgia D Tomaras5, Theresa M Wagner1, Lindsey R Baden6, Beryl A Koblin7, Nadine G Rouphael8, Spyros A Kalams9, Michael C Keefer10, Paul A Goepfert11, Magdalena E Sobieszczyk12, Kenneth H Mayer13, Edith Swann14, Hua-Xin Liao5, Barton F Haynes5, Barney S Graham15 and M Juliana McElrath4for the NIAID HIV Vaccine Trials Network

1Population Health Division, San Francisco Department of Public Health, San Francisco, CA, USA

2Department of Medicine, University of California, San Francisco, San Francisco, USA

3Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

5Human Vaccine Institute, Duke University, Durham, NC, USA

6Division of Infectious Disease, Brigham and Women’s Hospital, Boston, MA, USA

7Laboratory of Infectious Disease Prevention, New York Blood Center, New York, NY, USA

8The Hope Clinic, Division of Infectious Diseases, Emory University, Atlanta, GA, USA

9Infectious Diseases Division, Vanderbilt University School of Medicine, Nashville, TN, USA

10University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

11Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

12Division of Infectious Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA

13Fenway Health and the Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, USA

14Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA

15Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA

*Corresponding Author:
Jonathan D Fuchs
San Francisco Department of Public Health
25 Van Ness Ave, Suite 100
San Francisco, CA, 94102, USA
Tel: 01 415 336-1290
E-mail: [email protected]

Received date: April 09, 2015; Accepted date: May 12, 2015; Published date: May 23, 2015

Citation: Fuchs JD, Bart PA, Frahm N, Morgan C, Gilbert PB, et al. (2015) Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals. J AIDS Clin Res 6:461. doi:10.4172/2155-6113.1000461

Copyright: ©2015 Fuchs JD, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

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