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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 Response¹

Drew Weissman^2,*, Houping Ni^*, David Scales^*, Annie Dude^*, John Capodici^*, Karen McGibney^*, Asha Abdool^*, Stuart N. Isaacs^*, Georgetta Cannon^* and Katalin Karikó

Division of ^* Infectious Diseases and Neurosurgery, University of Pennsylvania, Philadelphia, PA 19096

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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