Universal Influenza T Cell-Targeted Mucosal Vaccines
Technical Report,01 May 2018,30 Apr 2019
Saint Louis University Saint Louis United States
Pagination or Media Count:
The goals of this work are to design and test novel T cell-targeted adenoviral Ad-based influenza vaccines with modified vector tropism designed to efficiently transduce dendritic cells DC. Drs. Curiel and Dmitriev WU generated multiple replication deficient GFP-expressing Ad vectors incorporating came lid nanobodies specific formurine antigen presenting cells CD40, Clec9a, and others. We tested the efficiencies of each using in vitro transduction assays in both total splenocytes and CD11c purified DC. We identified 2 different Ad vectors with enhanced DC transduction efficiencies. Control Ad and DC-targeted Ad vectors engineered to express conserved influenza CD4 and CD8 T cell epitopes are currently being generated and will soon be tested in HLA A2DR1 transgenic mice. Cloning of the synthetic multi-epitope influenza vaccine genes was straightforward, however, rescue and propagation of recombinant DC-targeted Ad was problematic. Drs. Curiel and Dmitriev have designed a workaround to suppress expression of the multi-epitope influenza vaccine gene during virus rescue and propagation, and we expect to have all novel vaccines ready for study within the next two months. We will determine whether mucosal delivery of these DC-directed T cell-targeted influenza vaccines provide superior immunogenicity and protection against multiple influenza subtypes in the next reporting period.