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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.
AuthorsS M Agwale, M T Shata, M S Reitz Jr, V S Kalyanaraman, R C Gallo, M Popovic, D M Hone
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 99 Issue 15 Pg. 10037-41 (Jul 23 2002) ISSN: 0027-8424 [Print] United States
PMID12096189 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • AIDS Vaccines
  • Gene Products, tat
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Immunoglobulin G
  • Protein Subunits
  • Vaccines, DNA
  • tat Gene Products, Human Immunodeficiency Virus
Topics
  • AIDS Vaccines (immunology)
  • Acquired Immunodeficiency Syndrome (immunology)
  • Animals
  • Antibody Specificity
  • CD8-Positive T-Lymphocytes
  • Cell Line
  • Female
  • Gene Products, tat (immunology)
  • HIV Antibodies (blood)
  • HIV Envelope Protein gp120 (immunology)
  • HIV Infections (immunology)
  • HIV-1 (immunology)
  • Humans
  • Immunity, Cellular
  • Immunoglobulin G (blood)
  • Mice
  • Mice, Inbred BALB C
  • Protein Subunits
  • Transfection
  • Vaccines, DNA (immunology)
  • tat Gene Products, Human Immunodeficiency Virus

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