|Title||Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Barouch DH, Liu J, Li H, Maxfield LF, Abbink P, Lynch DM, Iampietro JM, Sanmiguel A, Seaman MS, Ferrari G, Forthal DN, Ourmanov I, Hirsch VM, Carville A, Mansfield KG, Stablein D, Pau MG, Schuitemaker H, Sadoff JC, Billings EA, Rao M, Robb ML, Kim JH, Marovich MA, Goudsmit J, Michael NL|
|Date Published||2012 Feb 2|
|Keywords||Adenoviridae, AIDS Vaccines, Animals, Antibodies, Neutralizing, Enzyme-Linked Immunosorbent Assay, Female, HIV-1, Macaca mulatta, Male, Neutralization Tests, SAIDS Vaccines, Simian immunodeficiency virus, Viral Vaccines|
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.