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

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.
AuthorsGodwin Nchinda, David Amadu, Christine Trumpfheller, Olga Mizenina, Klaus Uberla, Ralph M Steinman
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 107 Issue 9 Pg. 4281-6 (Mar 2 2010) ISSN: 1091-6490 [Electronic] United States
PMID20160099 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • AIDS Vaccines
  • Gene Products, gag
  • Vaccines, DNA
  • AIDS Vaccines (administration & dosage, immunology)
  • Administration, Intranasal
  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes (immunology)
  • Gene Products, gag (chemistry, immunology)
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Vaccines, DNA (administration & dosage, immunology)

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