Vaccine Protection Against Acquisition of Neutralization-Resistant SIV Challenges in Rhesus Monkeys
Year of Publication
Barouch, D; Liu, J; Li H; Maxfield, LF; Abbink, P; Lynch, DM; Iampietro, M; San Miguel, A; Seaman, MS; Ferrari, G; Forthal D; Ourmanov, I; Hirsch, VM; Carville, A; Mansfield, K; Stablein, D; Pau,M; Schuitemaker, H; Sadoff, JC; Billings, EM; Rao, M
Adenoviridae/genetics; Adenoviridae/immunology; AIDS Vaccines/immunology; Animals Antibodies; Enzyme-Linked Immunosorbent Assay; Female; HIV-1/immunology; Macaca mulatta/immunology; Male; Neutralization Tests; Neutralizing/immunology
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.