Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen

Weaver, Eric A. and Lu, Zhongjing and Camacho, Zenadio T. and Moukdar, Fatiha and Liao, Hua-Xin and Ma, Ben-Jiang and Muldoon, Mark and Theiler, James and Nabel, Gary J. and Letvin, Norman L. and Korber, Bette T. and Hahn, Beatrice H. and Haynes, Barton F. and Gao, Feng (2006) Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen. Journal of Virology, 80 (14). pp. 6745-6756. ISSN 0022-538X

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Abstract

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.

Item Type:	Article
Additional Information:	Copyright © 2006, American Society for Microbiology.
Uncontrolled Keywords:	HIV vaccine, immunogen
Subjects:	MSC 2010, the AMS's Mathematics Subject Classification > 62 Statistics MSC 2010, the AMS's Mathematics Subject Classification > 92 Biology and other natural sciences
Depositing User:	Dr Mark Muldoon
Date Deposited:	18 Jul 2006
Last Modified:	20 Oct 2017 14:12
URI:	https://eprints.maths.manchester.ac.uk/id/eprint/391

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