Vaccine Protection Against Acquisition of Neutralization-Resistant SIV Challenges in Rhesus Monkeys
02/2012
Journal Article
Authors:
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.
Secondary:
Nature
Volume:
482
Pagination:
89-93
URL:
http://www.ncbi.nlm.nih.gov/pubmed/22217938
Keywords:
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
Abstract:
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.
