Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys.
The global diversity of HIV-1 represents a critical challenge facing HIV-1 vaccine development. HIV-1 mosaic antigens are bioinformatically optimized immunogens designed for improved coverage of HIV-1 diversity. However, the protective efficacy of such global HIV-1 vaccine antigens has not previously been evaluated. Here, we demonstrate the capacity of bivalent HIV-1 mosaic antigens to protect rhesus monkeys against acquisition of infection following heterologous challenges with the difficult-to-neutralize simian-human immunodeficiency virus SHIV-SF162P3. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing HIV-1 mosaic Env, Gag, and Pol afforded a significant reduction in the per-exposure acquisition risk following repetitive, intrarectal SHIV-SF162P3 challenges. Protection against acquisition of infection correlated with vaccine-elicited binding, neutralizing, and functional nonneutralizing antibodies, suggesting that the coordinated activity of multiple antibody functions may contribute to protection against difficult-to-neutralize viruses. These data demonstrate the protective efficacy of HIV-1 mosaic antigens and suggest a potential strategy for the development of a global HIV-1 vaccine. PAPERCLIP:
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Ragon Institute of MGH, Massachusetts Institute of Technology and Harvard, Boston, MA 02114, USA. Electronic address: dbarouch@bidmc.harvard.edu.
Dan H
DH
Barouch
Kathryn E
KE
Stephenson
Erica N
EN
Borducchi
Kaitlin
K
Smith
Kelly
K
Stanley
Anna G
AG
McNally
Jinyan
J
Liu
Peter
P
Abbink
Lori F
LF
Maxfield
Michael S
MS
Seaman
Anne-Sophie
AS
Dugast
Galit
G
Alter
Melissa
M
Ferguson
Wenjun
W
Li
Patricia L
PL
Earl
Bernard
B
Moss
Elena E
EE
Giorgi
James J
JJ
Szinger
Leigh Anne
LA
Eller
Erik A
EA
Billings
Mangala
M
Rao
Sodsai
S
Tovanabutra
Eric
E
Sanders-Buell
Mo
M
Weijtens
Maria G
MG
Pau
Hanneke
H
Schuitemaker
Merlin L
ML
Robb
Jerome H
JH
Kim
Bette T
BT
Korber
Nelson L
NL
Michael
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D005260:Female; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology; D007111:Immunity, Cellular; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D013047:Specific Pathogen-Free Organisms
D016915:AIDS Vaccines; D015488:HIV Antigens; D054298:Human Immunodeficiency Virus Proteins