HIV gag mRNA transfection of dendritic cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune response |
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Authors: | Weissman D Ni H Scales D Dude A Capodici J McGibney K Abdool A Isaacs S N Cannon G Karikó K |
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Institution: | Division of. Infectious Diseases and Neurosurgery, University of Pennsylvania, Philadelphia, PA 19096, USA. dreww@mail.med.upenn.edu |
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Abstract: | Dendritic cells (DC) are the major APCs involved in naive T cell activation making them prime targets of vaccine research. We observed that mRNA was efficiently transfected, resulting in superior translation in DC compared with other professional APCs. A single stimulation of T cells by HIV gag-encoded mRNA-transfected DC in vitro resulted in primary CD4(+) and CD8(+) T cell immune responses at frequencies of Ag-specific cells (5-12.5%) similar to primary immune responses observed in vivo in murine models. Additionally, mRNA transfection also delivered a maturation signal to DC. Our results demonstrated that mRNA-mediated delivery of encoded Ag to DC induced potent primary T cell responses in vitro. mRNA transfection of DC, which mediated efficient delivery of antigenic peptides to MHC class I and II molecules, as well as delivering a maturation signal to DC, has the potential to be a potent and effective anti-HIV T cell-activating vaccine. |
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