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

Eric A Weaver, Zhongjing Lu, Zenaido T. Camacho, Fatiha Moukdar, Hua Xin Liao, Ben Jiang Ma, Mark Muldoon, James Theiler, Gary J. Nabel, Norman L. Letvin, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes, Feng Gao

Research output: Contribution to journalArticle

54 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6745-6756
Number of pages12
JournalJournal of virology
Volume80
Issue number14
DOIs
StatePublished - Jul 1 2006

Fingerprint

Human immunodeficiency virus 1
HIV-1
Vaccines
T-lymphocytes
immune response
antigens
T-Lymphocytes
T-Lymphocyte Epitopes
vaccines
epitopes
env Genes
Cercopithecine Herpesvirus 1
Peptides
Recombinant DNA
Vaccinia virus
peptides
Major Histocompatibility Complex
recombinant DNA
Primates
Interferon-gamma

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

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

In: Journal of virology, Vol. 80, No. 14, 01.07.2006, p. 6745-6756.

Research output: Contribution to journalArticle

Weaver, EA, Lu, Z, Camacho, ZT, Moukdar, F, Liao, HX, Ma, BJ, Muldoon, M, Theiler, J, Nabel, GJ, Letvin, NL, Korber, BT, Hahn, BH, Haynes, BF & Gao, F 2006, 'Cross-subtype T-cell immune responses induced by a human immunodeficiency virus type 1 group M consensus env immunogen', Journal of virology, vol. 80, no. 14, pp. 6745-6756. https://doi.org/10.1128/JVI.02484-05
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. / Cross-subtype T-cell immune responses induced by a human immunodeficiency virus type 1 group M consensus env immunogen. In: Journal of virology. 2006 ; Vol. 80, No. 14. pp. 6745-6756.
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