Find in Library

<i>Shigella</i> spp. are responsible for bacillary dysentery or shigellosis transmitted via the fecal–oral route, causing significant morbidity and mortality, especially among vulnerable populations. There are currently no licensed <i>Shigella</i> vaccines. <i>Shigella</i> spp. use a type III secretion system (T3SS) to invade host cells. We have shown that L-DBF, a recombinant fusion of the T3SS needle tip (IpaD) and translocator (IpaB) proteins with the LTA1 subunit of enterotoxigenic <i>E. coli</i> labile toxin, is broadly protective against <i>Shigella</i> spp. challenge in a mouse lethal pulmonary model. Here, we assessed the effect of LDBF, formulated with a unique TLR4 agonist called BECC470 in an oil-in-water emulsion (ME), on the murine immune response in a high-risk population (young and elderly) in response to <i>Shigella</i> challenge. Dual RNA Sequencing captured the transcriptome during <i>Shigella</i> infection in vaccinated and unvaccinated mice. Both age groups were protected by the L-DBF formulation, while younger vaccinated mice exhibited more adaptive immune response gene patterns. This preliminary study provides a step toward identifying the gene expression patterns and regulatory pathways responsible for a protective immune response against <i>Shigella</i>. Furthermore, this study provides a measure of the challenges that need to be addressed when immunizing an aging population.