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

Authors

Eric A. Weaver, Duke University Medical Center, Durham & University of Nebraska-LincolnFollow
Zenaido T. Camacho, Duke University Medical Center, Durham
Fatiha Moukdar, Duke University Medical Center, Durham
Hua-Xin Liao, Duke University Medical Center, Durham
Ben-Jiang Ma, Duke University Medical Center, Durham
Mark Muldoon, University of Manchester, Manchester
James Theiler, Los Alamos National Laboratory, Los Alamos
Gary J. Nabel, Vaccine Research Center, NIAID, NIH
Norman L. Letvin, Harvard Medical School, Boston
Bette T. Korber, Los Alamos National Laboratory, Los Alamos & Santa Fe Institute, Santa Fe
Beatrice H. Hahn, University of Alabama at Birmingham, Birmingham
Barton F. Haynes, Duke University Medical Center, DurhamFollow
Feng Gao, Duke University Medical Center, DurhamFollow
Zhongjing Lu, Duke University Medical Center, Durham

Document Type

Article

Date of this Version

2006

Citation

JOURNAL OF VIROLOGY, July 2006, p. 6745–6756 Vol. 80, No. 14

doi:10.1128/JVI.02484-05

Comments

2006, American Society for Microbiology. All Rights Reserved.

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.