Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers

被引:214
作者
Ferrari, G
Humphrey, W
McElrath, MJ
Excler, JL
Duliege, AM
Clements, ML
Corey, LC
Bolognesi, DP
Weinhold, KJ
机构
[1] DUKE UNIV, MED CTR, DEPT SURG, DURHAM, NC 27710 USA
[2] DUKE UNIV, MED CTR, DEPT MICROBIOL, DURHAM, NC 27710 USA
[3] DUKE UNIV, MED CTR, DEPT IMMUNOL, DURHAM, NC 27710 USA
[4] UNIV WASHINGTON, DEPT MED, SEATTLE, WA 98195 USA
[5] PASTEUR MERIEUX CONNAUGHT LABS, F-92430 MARNES LA COQUETTE, FRANCE
[6] JOHNS HOPKINS UNIV, CTR IMMUNIZAT RES, BALTIMORE, MD 21205 USA
[7] CHIRON CORP, VACCINES, EMERYVILLE, CA 94608 USA
关键词
D O I
10.1073/pnas.94.4.1396
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A fundamental goal of current strategies to develop an efficacious vaccine for AIDS is the elicitation of broadly reactive cytotoxic T lymphocyte (CTL) reactivities capable of destroying virally infected targets, Recent application of recombinant canarypox ALVAC/HIV-1 vectors as vaccine immunogens in HIV-1, -noninfected volunteers has produced CTL responses in a significant number of vaccinees, Using a newly developed targeting strategy, we examined the capacity of vaccine-induced CTL to lyse autologous targets infected with a diverse group of viral isolates. CTL derived from recipients of a canarypox ALVAC/HIV-1 gp160 (MN) vaccine were found capable of lysing autologous CD4(+) lymphoblasts infected with the prototypic LAI strain of HIV-1. When tested against autologous targets infected with primary HIV-1 isolates representing genetically diverse vira clades, CTL from ALVAC/gp160 recipients showed both a broad pattern of cytolysis in which viruses from all clades tested were recognized as well as a highly restricted pattern in which no primary isolates, including clade B, were lysed, Differences in the HLA haplotypes of the volunteers immunized with the envelope vector might be a major determinant of the relative breadth of their CTL response, In contrast to ALVAC/gp160 vaccinees, recipients of the ALVAC/HIV-1 immunogen containing envelope as well as gag and protease genes consistently had CTL reactivities effective against a spectrum of primary isolate-infected targets, These studies demonstrate for the first time that clade B-based canarypox vaccines can elicit broad CTL reactivities capable of recognizing viruses belonging to genetically diverse HIV-1 clades, The results also reinforce the impact of viral core elements in the vaccine as well as the pattern of major histocompatibility complex class I allelic expression by the vaccine recipient in determining the relative breadth of the cellular response.
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收藏
页码:1396 / 1401
页数:6
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