Enhanced cellular immunity to SIV Gag following co-administration of adenoviruses encoding wild-type or mutant HIV Tat and SIV Gag.
Among candidate antigens for human immunodeficiency virus (HIV) prophylactic vaccines, the regulatory protein Tat is a critical early target, but has a potential for immune suppression. Adenovirus (Ad) recombinants encoding wild-type HIV Tat (Tat-wt) and a transdominant negative mutant HIV Tat (Tat22) were constructed and administered to mice separately or together with Ad-SIVgag. Immunogenicity and effects on immune responses to the co-administered Gag immunogen were evaluated. Wild-type and mutant Tat recombinants elicited similar Tat-specific cellular and humoral immune responses. Co-administration of either Tat immunogen with Ad-SIVgag induced modest but significant enhancement of Gag-specific interferon-gamma secreting T cells and lymphoproliferative responses. Neither the Ad-recombinant encoding Tat-wt nor Tat22 suppressed induction of anti-Tat or anti-Gag antibodies. Based on the immune responses observed in mice, both recombinants appear to be suitable vaccine candidates. Their contribution to protective efficacy remains to be determined in a non-human primate model.
Zhao
Jun
J
National Cancer Institute, 41 Medlars Drive, Building 41, Room D804, Bethesda, MD 20892-5065, USA.
Voltan
Rebecca
R
Peng
Bo
B
Davis-Warren
Alberta
A
Kalyanaraman
V S
VS
Alvord
W Gregory
WG
Aldrich
Kris
K
Bernasconi
Daniela
D
Buttò
Stefano
S
Cafaro
Aurelio
A
Ensoli
Barbara
B
Robert-Guroff
Marjorie
M
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001483:Base Sequence; D004274:DNA, Recombinant / Q000235:genetics; D005260:Female; D015683:Gene Products, gag / Q000235:genetics* / Q000276:immunology*; D015696:Gene Products, tat / Q000235:genetics* / Q000276:immunology*; D015750:Genes, gag; D015756:Genes, tat; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004274:DNA, Recombinant; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D015696:Gene Products, tat; D015483:HIV Antibodies; D014614:Vaccines, Synthetic; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma