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. |