Vaccine Protection Against Acquisition of Neutralization-Resistant SIV Challenges in Rhesus Monkeys

Preclinical studies of HIV-1 vaccine candidates have typically shown post-infection virologic control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges(1–3). Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant virus challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing SIVsmE543 Gag, Pol, and Env antigens resulted in a ≥80% reduction in the per-exposure probability of infection(4,5) against repetitive, intrarectal SIVmac251 challenges in rhesus monkeys. Protection against acquisition of infection exhibited distinct immunologic correlates as compared with post-infection virologic control and required the inclusion of Env in the vaccine regimen. These data demonstrate the first proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.