Cross-subtype T-cell immune responses induced by a human immunodeficiency virus type 1 group m consensus env immunogen.
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.
Weaver
Eric A
EA
Duke Human Vaccine Institute, Duke University Medical Center, 112 RPIII, Research Drive, Box 3347, DUMC, Durham, NC 27710, USA.
Lu
Zhongjing
Z
Camacho
Zenaido T
ZT
Moukdar
Fatiha
F
Liao
Hua-Xin
HX
Ma
Ben-Jiang
BJ
Muldoon
Mark
M
Theiler
James
J
Nabel
Gary J
GJ
Letvin
Norman L
NL
Korber
Bette T
BT
Hahn
Beatrice H
BH
Haynes
Barton F
BF
Gao
Feng
F
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D014644:Genetic Variation; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D015488:HIV Antigens; D006649:Histocompatibility Antigens; D010455:Peptides; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma