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
- *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.
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.