Long-term protection of chimpanzees against high-dose HIV-1 challenge induced by immunization.
A combination AIDS vaccine approach consisting of priming with adenovirus-HIV-1MN gp160 recombinants followed by boosting with HIV-1SF2 gp120 was evaluated in chimpanzees. Long-lasting protection, requiring only three immunizations, was achieved against a low-dose challenge with the SF2 strain of HIV-1 and a subsequent high-dose SF2 challenge administered 1 year later without an intervening boost. Notably, neutralizing antibody responses against both clinical and laboratory isolates developed in three chimpanzees and persisted until the time of high-dose challenge. The possibility that cytotoxic T-lymphocytes contribute to low-dose protection of a chimpanzee lacking neutralizing antibodies is suggested. Our results validate the live vector priming/subunit booster approach and should stimulate interest in assessing this combination vaccine approach in humans.
Lubeck
M D
MD
Wyeth-Ayerst Research, Radnor, PA 19087, USA.
Natuk
R
R
Myagkikh
M
M
Kalyan
N
N
Aldrich
K
K
Sinangil
F
F
Alipanah
S
S
Murthy
S C
SC
Chanda
P K
PK
Nigida
S M
SM
Markham
P D
PD
Zolla-Pazner
S
S
Steimer
K
K
Wade
M
M
Reitz
M S
MS
Arthur
L O
LO
Mizutani
S
S
Davis
A
A
Hung
P P
PP
Gallo
R C
RC
Eichberg
J
J
Robert-Guroff
M
M
D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000472:pathogenicity*; D002679:Pan troglodytes; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000008:administration & dosage
D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011993:Recombinant Fusion Proteins; D014612:Vaccines