Background:  Phase I studies in the United States suggest that the VRC multiclade HIV-1 DNA vaccine (clade B Gag, Pol, and Nef, and Env from clades A, B, and C) followed by the VRC multiclade HIV-1 recombinant serotype 5 adenoviral vector vaccine (4 vectors encoding a clade B Gag/Pol fusion and clades A, B, and C Env) is well tolerated and immunogenic. This randomized, double-blind, placebo-controlled study is evaluating the safety and immunogenicity of this regimen and the VRC multiclade HIV-1 recombinant adenoviral vector vaccine alone in African adults.

Methods:  Healthy adults aged 18 to 50 in Kigali, Rwanda and Nairobi, Kenya were randomized to receive a single intramuscular injection of 1x10¹⁰ or 1x10¹¹ particle units of the VRC multiclade HIV-1 recombinant adenoviral vector vaccine (rAd5) at week 0, or the VRC multiclade HIV-1 DNA vaccine (DNA) 4-mg dose at weeks 0, 4, and 8, followed by rAd5 at 1x10¹⁰ or 1x10¹¹ doses at week 24, or placebo, in a 3:1 vaccine:placebo ratio for each group. Volunteers were followed for 1 year. Safety and tolerability were assessed clinically and by routine lab tests. Immunogenicity was evaluated by the interferon-gamma (IFN-γ) ELISpot assay.

Results:  We randomized 35 people to receive rAd5 alone or placebo, and 79 people to receive DNA prime-rAd5 boost regimen or placebo. The study is ongoing; preliminary blinded safety and unblinded immunogenicity data are presented. The vaccines were generally well tolerated in all groups. Injection-site reactions were common after both DNA/placebo and rAd5/placebo, with most rated as mild. After rAd5 alone or placebo, of 35 systemic reactions, 18 were mild, 7 were moderate, and none were severe. After DNA prime-rAd5 boost or placebo, of 42 systemic reactions, 20 were mild, 7 were moderate, and 2 were severe (1 headache, 1 malaise). Systemic reactions were all self-limited and not more common or severe after rAd5 than after DNA. The 1 serious adverse event—partial, subjective, bilateral hearing loss—was assessed as possibly vaccine-related. Overall, 6 of 12 volunteers in the rAd5 10¹⁰ group, 6 of 12 in the rAd5 10¹¹ group, and 0 of 11 in the placebo group had positive ELISpot responses. ELISpot responses in volunteers receiving rAd after DNA priming have not yet been measured.

Conclusions:  Preliminary safety data suggest that the VRC multiclade HIV-1 DNA and recombinant multiclade HIV-1 adenoviral vector vaccines were generally safe and well tolerated at all doses studied.  Both rAd5 dose levels were immunogenic.