Abstract
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. 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. 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. 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.
Highlights
The development of a safe and effective preventive HIV vaccine remains an urgent public health priority in the setting of an estimated 2.1 million new infections globally [1]
A multiclade/ multigene DNA prime, Recombinant adenovirus serotype 5 (rAd5) boost regimen encoding HIV-1 Gag, Pol, and Nef from clade B, and Env from clades A, B, and C developed by the NIAID Vaccine Research Center (VRC) was immunogenic in early phase trials [11,12]
Rates were highest among rAd35/ rAd5 vaccinees (81.8%) and lowest among participants who received DNA/rAd5 (45.7%)
Summary
The development of a safe and effective preventive HIV vaccine remains an urgent public health priority in the setting of an estimated 2.1 million new infections globally [1]. A multiclade/ multigene DNA prime, rAd5 boost regimen encoding HIV-1 Gag, Pol, and Nef from clade B, and Env from clades A, B, and C developed by the NIAID Vaccine Research Center (VRC) was immunogenic in early phase trials [11,12]. The recent HVTN 505 phase 2b trial (NCT00865566) evaluating this regimen failed to show reduced HIV acquisition or viral load setpoint in Ad5-seronegative, circumcised men who have sex with men and transgender women from the United States [7] Even if such a vaccine were shown effective in this targeted population, preexisting neutralizing antibodies to Ad5 globally are highly prevalent, in the developing world [13,14,15,16]. The placebos for the adenovectors and DNA vaccines were final formulation buffer and phosphate-buffered saline (PBS), respectively
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