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.
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Authors | S M Agwale, M T Shata, M S Reitz Jr, V S Kalyanaraman, R C Gallo, M Popovic, D M Hone |
Journal | Proceedings 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 |
PMID | 12096189
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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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
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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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