Long-term protection of chimpanzees against high-dose HIV-1 challenge induced by immunization

被引:137
作者
Lubeck, MD
Natuk, R
Myagkikh, M
Kalyan, N
Aldrich, K
Sinangil, F
Alipanah, S
Murthy, SCS
Chanda, PK
Nigida, SM
Markham, PD
ZollaPazner, S
Steimer, K
Wade, M
Reitz, MS
Arthur, LO
Mizutani, S
Davis, A
Hung, PP
Gallo, RC
Eichberg, J
RobertGuroff, M
机构
[1] WYETH AYERST RES,RADNOR,PA 19087
[2] NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892
[3] CHIRON CORP,EMERYVILLE,CA 94608
[4] NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21702
[5] ADV BIOSCI LABS,KENSINGTON,MD 20895
[6] VET AFFAIRS MED CTR,NEW YORK,NY 10010
关键词
D O I
10.1038/nm0697-651
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A combination AIDS vaccine approach consisting of priming with adenovirus-HIV-1(MN)gp160 recombinants followed by boosting with HIV-1(SF2)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 row-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.
引用
收藏
页码:651 / 658
页数:8
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