cellular immunity, gag, HIV, dendritic cell, toll like receptor 3, vaccine
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.
Trumpfheller, C., M. Caskey, G. Nchinda, M. P. Longhi, O. Mizenina, Y. Huang, S. J. Schlesinger, M. Colonna, and R. M. Steinman. 2008. "The Microbial Mimic Poly IC Induces Durable and Protective CD4+ T Cell Immunity Together with a Dendritic Cell Targeted Vaccine." Proceedings of the National Academy of Sciences of the United States of America 105 (7): 2574-2579