The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine

Christine Trumpfheller, Marina Caskey, Godwin Nchinda, Maria Paula Longhi, Olga Mizenina, Yaoxing Huang, Sarah J. Schlesinger, Marco Colonna, Ralph M. Steinman

Research output: Contribution to journalArticlepeer-review

227 Scopus citations

Abstract

CD4+ Th1 type immunity is implicated in resistance to global infectious diseases. To improve the efficacy of T cell immunity induced by human immunodeficiency virus (HIV) vaccines, we are developing a protein-based approach that directly harnesses the function of dendritic cells (DCs) in intact lymphoid tissues. Vaccine proteins are selectively delivered to DCs by antibodies to DEC-205/CD205, a receptor for antigen presentation. We find that polyriboinosinic: polyribocytidylic acid (poly IC) independently serves as an adjuvant to allow a DC-targeted protein to induce protective CD4+ T cell responses at a mucosal surface, the airway. After two doses of DEC-targeted, HIV gag p24 along with poly IC, responder CD4+ T cells have qualitative features that have been correlated with protective function. The T cells simultaneously make IFN-γ, tumor necrosis factor (TNF)-α, and IL-2, and in high amounts for prolonged periods. The T cells also proliferate and continue to secrete IFN-γ in response to HIV gag p24. The adjuvant role of poly IC requires Toll-like receptor (TLR) 3 and melanoma differentiation-associated gene-5 (MDA5) receptors, but its analog poly IC 12U requires only TLR3. We suggest that poly IC be tested as an adjuvant with DC-targeted vaccines to induce numerous multifunctional CD4 + Th1 cells with proliferative capacity.

Original languageEnglish
Pages (from-to)2574-2579
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number7
DOIs
StatePublished - Feb 19 2008

Keywords

  • Adjuvant
  • Gag
  • HIV
  • MDA5
  • TLR3

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