The University of Delaware was awarded a $2,812,558 Trans-NIH Research Support Project Grant from the National Institutes of Health Office of the Director to develop an oral vaccine delivery platform utilizing nitrated bacterial antigens displayed on Bacillus subtilis spores. The three-year project aims to advance the understanding of how nitration can enhance the immunogenicity of weakly immunogenic bacterial antigens from pathogens like Shigella. Researchers will perform animal studies using Shigella invasion proteins and develop high-throughput methods to screen antigen preferences of MHC-II molecules to identify optimal residue placement for immune recognition of unnatural peptide ligands. Tools will also be developed to enable site-specific incorporation of immunogenic amino acids within proteins fused to the spore coat to leverage B. subtilis spores as an oral delivery system. Insights gained from this work seek to establish a technology platform for shelf-stable, orally-administered immunization using nitrated residues to overcome current limitations in vaccine development, manufacturing, and administration.
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