Targeting the NS4b antigen of West Nile Virus to the endocytic receptor DEC-205 to stimulate protective T cell responses to West Nile Virus encephalitis
Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B772
Abstract ID: 5835
Presenting Author:
Joshua D Herzler , Graduate Student at Cal Poly, Pomona
Abstract:
West Nile Virus (WNV), the primary cause of mosquito-borne neuroinvasive disease in the US, poses a significant public health threat without an approved human vaccine. DCs are pivotal in orchestrating immune responses, dictating antigen-specific effector T cell activation or tolerance based on their maturity. The endocytic receptor DEC-205, expressed by specific DC subsets, facilitates antigen uptake, processing, and cross-presentation, initiating an effective T cell response. Studies highlight DEC-205+ DCs within the CNS in reactivating antiviral effector T cell responses, restricting WNV replication, and mitigating immunopathology. We propose targeting antigens to these DCs to enhance antiviral immunity against WNV within the CNS, fusing antigens to DEC-205-specific monoclonal antibodies (mAbs). A DEC-205-targeted hybrid antibody will be developed, conjugating the WNV NS4b immunodominant peptide to a DEC-205 mAb. Subsequent purification will precede testing therapeutic efficacy in a murine WNV encephalitis model. Delivering the aDEC-205 hybrid mAb with DC maturation stimulus (poly I:C), we will assess co-stimulatory molecule expression (CD40, CD80, and CD86) on DCs and evaluate T cell activation through activation marker expression and cytokine production. This research introduces a vaccination approach against West Nile Virus encephalitis, leveraging targeted antigen delivery to DEC-205+ DCs, offering insights into potential therapeutic and preventive strategies.
Targeting the NS4b Antigen of West Nile Virus to the Endocytic Receptor DEC-205 to Stimulate Protective T Cell Responses to West Nile Virus Encephalitis
Category
Poster and Podium (Block Symposium)