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

Dan H. Barouch*, Jinyan Liu, Hualin Li, Lori F. Maxfield, Peter Abbink, Diana M. Lynch, M. Justin Iampietro, Adam Sanmiguel, Michael S. Seaman, Guido Ferrari, Donald N. Forthal, Ilnour Ourmanov, Vanessa M. Hirsch, Angela Carville, Keith G. Mansfield, Donald Stablein, Maria G. Pau, Hanneke Schuitemaker, Jerald C. Sadoff, Erik A. BillingsMangala Rao, Merlin L. Robb, Jerome H. Kim, Mary A. Marovich, Jaap Goudsmit, Nelson L. Michael

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

392 Scopus citations

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.

Original languageEnglish
Pages (from-to)89-93
Number of pages5
JournalNature
Volume482
Issue number7383
DOIs
StatePublished - 2 Feb 2012
Externally publishedYes

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