Cross-subtype T-cell immune responses induced by a human immunodeficiency virus type 1 group M consensus env immunogen

被引:61
作者
Weaver, Eric A.
Lu, Zhongjing
Camacho, Zenaido T.
Moukdar, Fatiha
Liao, Hua-Xin
Ma, Ben-Jiang
Muldoon, Mark
Theiler, James
Nabel, Gary J.
Letvin, Norman L.
Korber, Bette T.
Hahn, Beatrice H.
Haynes, Barton F.
Gao, Feng
机构
[1] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA
[2] Univ Manchester, Sch Math, Manchester, Lancs, England
[3] Los Alamos Natl Lab, Los Alamos, NM 87545 USA
[4] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
[5] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA
[6] Santa Fe Inst, Santa Fe, NM 87501 USA
[7] Univ Alabama, Dept Med, Birmingham, AL 35294 USA
[8] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA
关键词
D O I
10.1128/JVI.02484-05
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic group M consensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide sets from heterologous subtype A, B, and C viruses. The CON6-derived vaccine was immunogenic and induced a greater number of T-cell epitope responses than any single wild-type subtype A, B, and C env immunogen and similar T-cell responses to a polyvalent vaccine. The responses were comparable to within-clade responses but significantly more than between-clade responses. The magnitude of the T-cell responses induced by CON6 (measured by individual epitope peptides) was also greater than the magnitude of responses induced by individual wild-type env immunogens. Though the limited major histocompatibility complex repertoire in inbred mice does not necessarily predict responses in nonhuman primates and humans, these results suggest that synthetic centralized env immunogens represent a promising approach for HIV-1 vaccine design that merits further characterization.
引用
收藏
页码:6745 / 6756
页数:12
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