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


Journal Article

Barouch, D.; Liu, J.; H, L.; Maxfield, L.F.; Abbink, P.; Lynch, D.M.; Iampietro, M.; San Miguel, A.; Seaman, M.S.; Ferrari, G.; D, F.; Ourmanov, I.; Hirsch, V.M.; Carville, A.; Mansfield, K.; Stablein, D.; Pau, M.; Schuitemaker, H.; Sadoff, J.C.; Billings, E.M.; 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.

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