gag protein, AIDS vaccines, HIV, DNA vaccine, Yersinia pestis
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.
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