A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice
- S. M. Agwale*,
- M. T. Shata*,
- M. S. Reitz, Jr.†,
- V. S. Kalyanaraman‡,
- R. C. Gallo†,
- M. Popovic†, and
- D. M. Hone*,§
- Divisions of *Vaccine Research and †Basic Science, Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, MD 21202; and ‡Advanced BioScience Laboratories, Kensington, MD 20895
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Contributed by R. C. Gallo
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-γ 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-γ -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.
Footnotes
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↵ § To whom reprint requests should be addressed. E-mail: hone{at}umbi.umd.edu.
- Abbreviations:
- DC,
- dendritic cell;
- IFN-γ–ELISPOT,
- IFN-γ-specific enzyme-linked immunospot
- Copyright © 2002, The National Academy of Sciences
