A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice.
The rational design of new therapies against HIV-1 necessitates an improved understanding of the mechanisms underlying the production of ineffective immune responses to HIV-1 in most infected individuals. This report shows that the CD8(+) T cell responses to gp120 were greatly diminished in mice vaccinated with a bicistronic gp120-Tat DNA vaccine, compared with those induced by a DNA vaccine encoding gp120 alone. The CD8(+) T cell responses induced by the latter included strong gp120-specific IFN-gamma secretion and protective antiviral immunity against challenge by a vaccinia-env pseudotype. The degree to which Tat influenced CD8(+) T cell responses depended on the bioactivity of Tat. Thus, a bicistronic DNA vaccine that expresses gp120 and a truncated Tat defective for LTR activation elicited strong IFN-gamma -secreting CD8(+) T cell responses to gp120 but conferred only marginal protection against the vaccinia-env challenge. The effect of Tat was completely blocked, however, by immunization with inactivated Tat protein before vaccination with the bicistronic gp120-Tat DNA vaccine.
Agwale
S M
SM
Division of Vaccine Research, Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, MD 21202, USA.
Shata
M T
MT
Reitz
M S
MS
Kalyanaraman
V S
VS
Gallo
R C
RC
Popovic
M
M
Hone
D M
DM
D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity; D018414:CD8-Positive T-Lymphocytes; D002460:Cell Line; D005260:Female; D015696:Gene Products, tat / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D021122:Protein Subunits; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015696:Gene Products, tat; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D021122:Protein Subunits; D019444:Vaccines, DNA; D054322:tat Gene Products, Human Immunodeficiency Virus