Document Type
Article
Publication Date
2010
Keywords
gag protein, AIDS vaccines, HIV, DNA vaccine, Yersinia pestis
Abstract
To improve the efficacy of T cell-based vaccination, we pursued the principle that CD4+ T cells provide help for functional CD8 + T cell immunity. To do so, we administered HIV gag to mice successively as protein and DNA vaccines. To achieve strong CD4+ T cell immunity, the protein vaccine was targeted selectively to DEC-205, a receptor for antigen presentation on dendritic cells. This targeting helped CD8+ T cell immunity develop to a subsequent DNA vaccine and improved protection to intranasal challenge with recombinant vaccinia gag virus, including more rapid accumulation of CD8+ T cells in the lung. The helper effect of dendritic cell-targeted protein vaccine wasmimicked by immunization with specificMHCII binding HIV gag peptides but not peptides from a disparate Yersinia pestis microbe. CD4+ helper cells upon adoptive transfer allowed wild-type, but not CD40-/-, recipient mice to respond better to the DNA vaccine. The transfer also enabled recipients to more rapidly accumulate gagspecific CD8+ T cells in the lung following challenge with vaccinia gag virus. Thus, complementary prime boost vaccination, in which prime and boost favor distinct types of T cell immunity, improves plasmid DNA immunization, including mobilization of CD8+ T cells to sites of infection.
Recommended Citation
Nchinda, G., D. Amadu, C. Trumpfheller, O. Mizenina, K. Überla, and R. M. Steinman. 2010. "Dendritic Cell Targeted HIV Gag Protein Vaccine Provides Help to a DNA Vaccine Including Mobilization of Protective CD8+ T Cells." Proceedings of the National Academy of Sciences of the United States of America 107 (9): 4281-4286
Comments
Open Access