Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys.
Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIV(SME543) Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection against repetitive, intrarectal SIV(MAC251) challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.
Barouch, DH; Liu, J; Li, H; Maxfield, LF; Abbink, P; Lynch, DM; Iampietro, MJ; SanMiguel, A; Seaman, MS; Ferrari, G; Forthal, DN; Ourmanov, I; Hirsch, VM; Carville, A; Mansfield, KG; Stablein, D; Pau, MG; Schuitemaker, H; Sadoff, JC; Billings, EA; Rao, M; Robb, ML; Kim, JH; Marovich, MA; Goudsmit, J; Michael, NL
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