Recombinant Mycobacterium bovis bacillus Calmette-Guerin elicits human immunodeficiency virus type 1 envelope-specific T lymphocytes at mucosal sites.
A successful vaccine vector for human immunodeficiency virus type 1 (HIV-1) should induce anti-HIV-1 T-cell immune responses at mucosal sites. We have constructed recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) expressing an HIV-1 group M consensus envelope (Env) either as a surface, intracellular, or secreted protein as an immunogen. rBCG containing HIV-1 env plasmids engineered for secretion induced optimal Env-specific T-cell gamma interferon enzyme-linked immunospot responses in murine spleen, female reproductive tract, and lungs. While rBCG-induced T-cell responses to HIV-1 envelope in spleen were lower than those induced by adenovirus prime/recombinant vaccinia virus (rAd-rVV) boost, rBCG induced comparable responses to rAd-rVV immunization in the female reproductive tract and lungs. T-cell responses induced by rBCG were primarily CD4(+), although rBCG alone did not induce anti-HIV-1 antibody. However, rBCG could prime for a protein boost by HIV-1 envelope protein. Thus, rBCG can serve as a vector for induction of anti-HIV-1 consensus Env cellular responses at mucosal sites.
Yu
Jae-Sung
JS
Human Vaccine Institute and Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710 , USA.
Peacock
James W
JW
Jacobs
William R
WR
Frothingham
Richard
R
Letvin
Norman L
NL
Liao
Hua-Xin
HX
Haynes
Barton F
BF
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D015686:Gene Products, env / Q000276:immunology / Q000494:pharmacology; D005836:Genitalia, Female / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014614:Vaccines, Synthetic / Q000276:immunology / Q000494:pharmacology; D054299:env Gene Products, Human Immunodeficiency Virus
D000914:Antibodies, Viral; D001500:BCG Vaccine; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; D007371:Interferon-gamma