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A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice.


ABSTRACT: 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.

SUBMITTER: Agwale SM 

PROVIDER: S-EPMC126620 | biostudies-literature | 2002 Jul

REPOSITORIES: biostudies-literature

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A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice.

Agwale S M SM   Shata M T MT   Reitz M S MS   Kalyanaraman V S VS   Gallo R C RC   Popovic M M   Hone D M DM  

Proceedings of the National Academy of Sciences of the United States of America 20020702 15


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 IF  ...[more]

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