|BRADSHAW, DAVID - Oak Ridge Institute For Science And Education (ORISE)
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/27/2023
Publication Date: N/A
Technical Abstract: Non-typhoidal Salmonella is among the most important pathogens causing foodborne illnesses in humans. Contaminated food animal products (such as poultry) are a main source of Salmonella infections. Reduction of Salmonella loads in food animals via vaccination is a valuable intervention tool to reduce food chain transmission; however, a major limitation of current Salmonella vaccines is the lack of cross-protection against the >2600 serovars of Salmonella. Multiepitope vaccines are a viable vaccination strategy that express multiple, statistically chosen, antigenic epitopes across various bacterial proteins, thereby strategically activating a wider array of cellular and humoral immune responses in the vaccinated host. These epitopes can be identified with reverse vaccinology which utilizes in silico tools and filters to screen proteins for epitopes to use in vaccine construction. In the current study, reverse vaccinology was utilized to identify homologous epitopes across poultry-relevant serovars for development of a cross-protective vaccine against Salmonella. The Salmonella enterica subspecies enterica serovar Typhimurium strain UK-1 proteome was used in a reverse vaccinology pipeline. Various in silico tools identified non-flagellar, -LPS, -plasmid, and -phage proteins (extracellular, periplasmic, or outer membrane) with high adhesion probability, 0-1 transmembrane helices, high antigenicity, negative homology to six potential hosts, and positive homology to five serovars representing four serogroups (B-E) of Salmonella enterica. The resulting 100 proteins were used as inputs into additional in silico tools to find unique epitopes with strong binding to chicken-like human major histocompatibility complex (MHC) alleles, high antigenicity/immunogenicity, non-toxicity, hydrophilicity, and 100% homology to poultry-relevant serovars. The 75 MHC class I and 226 MHC class II identified epitopes will be used to construct cross-serovar-protective, multiepitope vaccines to evaluate in silico and in vivo with the ultimate goal of developing an effective vaccine against multiple serogroups to reduce Salmonella in poultry and improve food safety.