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Journal of Virology, July 2006, p. 6745-6756, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.02484-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina 27710,¹ School of Mathematics, University of Manchester, Manchester, United Kingdom,² Los Alamos National Laboratory, Los Alamos, New Mexico 87545,³ Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892,⁴ Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115,⁵ Santa Fe Institute, Santa Fe, New Mexico 87501,⁶ Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294⁷

Received 25 November 2005/ Accepted 21 April 2006

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.

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