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

Feb-12

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:
<p>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.</p>

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