Journal article
Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.
- Fuchs JD Population Health Division, San Francisco Department of Public Health, San Francisco, CA, USA ; Department of Medicine, University of California, San Francisco, San Francisco, USA.
- Bart PA Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Frahm N Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
- Morgan C Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
- Gilbert PB Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
- Kochar N Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
- DeRosa SC Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
- Tomaras GD Human Vaccine Institute, Duke University, Durham, NC, USA.
- Wagner TM Population Health Division, San Francisco Department of Public Health, San Francisco, CA, USA.
- Baden LR Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA.
- Koblin BA Laboratory of Infectious Disease Prevention, New York Blood Center, New York, NY, USA.
- Rouphael NG The Hope Clinic, Division of Infectious Diseases, Emory University, Atlanta, GA, USA.
- Kalams SA Infectious Diseases Division, Vanderbilt University School of Medicine, Nashville, TN, USA.
- Keefer MC University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
- Goepfert PA Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
- Sobieszczyk ME Division of Infectious Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA.
- Mayer KH Fenway Health and the Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, USA.
- Swann E Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
- Liao HX Human Vaccine Institute, Duke University, Durham, NC, USA.
- Haynes BF Human Vaccine Institute, Duke University, Durham, NC, USA.
- Graham BS Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
- McElrath MJ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
- 2015-11-21
Published in:
- Journal of AIDS & clinical research. - 2015
English
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.
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.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.4172/2155-6113.1000461
- PMID 26587311
- Persistent URL
- https://sonar.ch/global/documents/186223
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