Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys

Article

关键词: CELLULAR IMMUNE-RESPONSES;    LOW-DOSE CHALLENGE;    INFECTION;    ANTIBODIES;    MACAQUES;    VECTORS;    MEMORY;    BREADTH;   

DOI  :  10.1038/nature10766

来源: SCIE

【 摘 要 】

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(1-3). 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 SIVSME543 Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection(4,5) against repetitive, intrarectal SIVMAC251 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.

【 授权许可】

Free