Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys.
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.
Division of Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. dbarouch@bidmc.harvard.edu
Dan H
DH
Barouch
Jinyan
J
Liu
Hualin
H
Li
Lori F
LF
Maxfield
Peter
P
Abbink
Diana M
DM
Lynch
M Justin
MJ
Iampietro
Adam
A
SanMiguel
Michael S
MS
Seaman
Guido
G
Ferrari
Donald N
DN
Forthal
Ilnour
I
Ourmanov
Vanessa M
VM
Hirsch
Angela
A
Carville
Keith G
KG
Mansfield
Donald
D
Stablein
Maria G
MG
Pau
Hanneke
H
Schuitemaker
Jerald C
JC
Sadoff
Erik A
EA
Billings
Mangala
M
Rao
Merlin L
ML
Robb
Jerome H
JH
Kim
Mary A
MA
Marovich
Jaap
J
Goudsmit
Nelson L
NL
Michael
D016915:AIDS Vaccines / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015497:HIV-1 / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology*; D008297:Male; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D018449:SAIDS Vaccines; D014765:Viral Vaccines