Targeting West Nile Virus NS4b antigen with DEC-205-specific scFv to stimulate protective T-cell responses 4142

Abstract Description West Nile Virus (WNV), the leading cause of mosquito-borne neuroinvasive disease in the US, remains a significant public health challenge without an approved human vaccine. Dendritic cells (DCs) are crucial for initiating immune responses, with antigen uptake, processing, and cross-presentation mediated by the endocytic receptor DEC-205, expressed by specific DC subsets. DEC-205+ DCs within the CNS are critical for reactivating antiviral effector T cells, restricting WNV replication, and reducing immunopathology. To harness this pathway, we propose targeting antigens to DEC-205+ DCs using a single-chain variable fragment (scFv) specific to DEC-205. By conjugating the WNV NS4b immunodominant peptide to this scFv, we aim to deliver the antigen efficiently to DEC-205+ DCs. This targeted approach will be tested in a murine model of WNV encephalitis. Co-administration with a DC maturation stimulus (poly I:C) will be used to enhance the immune response. We will assess the therapeutic efficacy by evaluating DC maturation (CD40, CD80, CD86 expression) and T cell activation markers and cytokine production. This research highlights a novel strategy for vaccine development against WNV encephalitis by leveraging targeted antigen delivery via DEC-205-specific scFv, offering potential advances in therapeutic and preventive interventions. Topic Categories Vaccines and Immunotherapy (VAC)