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Publication : Dendritic cell targeted HIV gag protein vaccine provides help to a DNA vaccine including mobilization of protective CD8+ T cells.

First Author  Nchinda G Year  2010
Journal  Proc Natl Acad Sci U S A Volume  107
Issue  9 Pages  4281-6
PubMed ID  20160099 Mgi Jnum  J:158571
Mgi Id  MGI:4439188 Doi  10.1073/pnas.1000621107
Citation  Nchinda G, et al. (2010) Dendritic cell targeted HIV gag protein vaccine provides help to a DNA vaccine including mobilization of protective CD8+ T cells. Proc Natl Acad Sci U S A 107(9):4281-6
abstractText  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 was mimicked by immunization with specific MHC II 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 gag-specific 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.
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