Vaccine protection against acquisition of neutralization resistant SIV challenge
Vaccine protection against acquisition of neutralization resistant SIV challenge.Dan H. Barouch,1, 2 Jinyan Liu,1 Hualin Li,1 Lori F. Maxfield,1 Peter Abbink,1 Diana M. Lynch,1 M. Justin Iampietro,1 Adam SanMiguel,1 Michael S. Seaman,1 Guido Ferrari,3 Donald N. Forthal,4 Ilnour Ourmanov,5 Vanessa M. Hirsch,5 Angela Carville,6 Keith G. Mansfield,6 Donald Stablein,7 Maria G. Pau,8 Hanneke Schuitemaker,8 Jerald C. Sadoff,8 Erik M. Billings,9 Mangala Rao,9 Merlin L. Robb,9 Jerome H. Kim,9 Mary A. Marovich,9Jaap Goudsmit8, 10& Nelson L. Michael9, 10et al.Journal name: Nature Year published: (2012) DOI: doi:10.1038/nature10766 Received 29 September 2011 Accepted 07 December 2011 Published online 04 January 2012
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 challenges1, 2, 3. 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 SIVSME543 Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection4, 5 against repetitive, intrarectal SIVMAC251 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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