Oral administration of sEVs from Salmonella-infected macrophages provides antigen-specific adaptive immunity in vivo 4496

Abstract Description Salmonella enterica serovar Typhimurium is a non-typhoidal bacterium that is acquired through the consumption of contaminated food or water, leading to gastrointestinal disease. Salmonella can survive and replicate intracellularly in macrophages(MΦ), allowing the MΦ to release particles known as small extracellular vesicles(sEVs), which play a role in intercellular communication. We have previously identified the presence of several Salmonella effector proteins: SopB, CirA, and OmpA in sEVs derived from Salmonella-infected MΦ through proteomics. Our previous experiments have shown that sEVs from Salmonella-infected MΦ dosed intranasally stimulate SIgA production and provide memory CD4+ T cell responses against S. Typhimurium in vivo. To demonstrate antigen-specific adaptive immunity against oral sEV administration, which is more clinically relevant for Salmonella pathogenesis and vaccine development, mice were dosed with host sEVs derived from Salmonella-infected MΦ orally. Results showed an increasing serum IgG titer against OmpA and CirA antigens. After the last sEV booster dose, mice were challenged with S. Typhimurium for 24 hours. Mice dosed with sEVs had higher survival rates compared to PBS, and an increase in IFNγ and IL-2 expressing memory CD4+ T cells from mesenteric lymph nodes stimulated with Salmonella. Collectively, antigen-specific IgG production as well as memory T cell activation demonstrated the efficacy of sEVs as a vaccine candidate against S. Typhimurium. Funding Sources Supported by NIH fund, National Institute of Allergy and Infectious Diseases No 1R03AI135610-01A1 and R01 AI158749-02 Topic Categories Vaccines and Immunotherapy (VAC)