Jonathan D Fuchs1, Pierre-Alexandre Bart2, Nicole Frahm3, Cecilia Morgan3, Peter B Gilbert3, Nidhi Kochar3, Stephen C DeRosa3, Georgia D Tomaras4, Theresa M Wagner5, 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 Liao4, Barton F Haynes4, Barney S Graham15, M Juliana McElrath3. 1. Population Health Division, San Francisco Department of Public Health, San Francisco, CA, USA ; Department of Medicine, University of California, San Francisco, San Francisco, USA. 2. Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 3. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 4. Human Vaccine Institute, Duke University, Durham, NC, USA. 5. Population Health Division, San Francisco Department of Public Health, San Francisco, CA, USA. 6. Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA. 7. Laboratory of Infectious Disease Prevention, New York Blood Center, New York, NY, USA. 8. The Hope Clinic, Division of Infectious Diseases, Emory University, Atlanta, GA, USA. 9. Infectious Diseases Division, Vanderbilt University School of Medicine, Nashville, TN, USA. 10. University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. 11. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. 12. Division of Infectious Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA. 13. Fenway Health and the Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, USA. 14. Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. 15. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
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 fourHIV-1 vaccine/placebogroups: 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.
RCT Entities:
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-uninfectedparticipants 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.
Entities:
Keywords:
Adenovirus 35; Adenovirus 5; DNA vaccine; HIV Vaccine; Randomized clinical trial
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