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

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

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