title: Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity.
abstract: The emergence of multidrug-resistant Klebsiella pneumoniae highlights the need to develop preventive measures to ameliorate Klebsiella infections. Bacteria-derived extracellular vesicles (EVs) are spherical nanometer-sized proteolipids enriched with outer membrane proteins. Gram-negative bacteria-derived EVs have gained interest for use as nonliving complex vaccines. In the present study, we evaluated whether K. pneumoniae-derived EVs confer protection against bacteria-induced lethality. K. pneumoniae-derived EVs isolated from in vitro bacterial culture supernatants induced innate immunity, including the upregulation of co-stimulatory molecule expression and proinflammatory mediator production. EV vaccination via the intraperitoneal route elicited EV-reactive antibodies and interferon-gamma-producing T-cell responses. Three vaccinations with the EVs prevented bacteria-induced lethality. As verified by sera and splenocytes adoptive transfer, the protective effect of EV vaccination was dependent on both humoral and cellular immunity. Taken together, these findings suggest that K. pneumoniae-derived EVs are a novel vaccine candidate against K. pneumoniae infections.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: Won-Hee
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: Hyun-Il
authors.initials: HI
authors.lastname: Choi
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: Sung-Wook
authors.initials: SW
authors.lastname: Hong
authors.affiliation: Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
authors.forename: Kwang-Sun
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.affiliation: Research Institute, AEON Medix, Inc, Pohang, Republic of Korea.
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Jeon
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology / Q000382:microbiology* / Q000627:therapeutic use*; D000067128:Extracellular Vesicles / Q000276:immunology / Q000382:microbiology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology; D007710:Klebsiella Infections / Q000276:immunology / Q000517:prevention & control*; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008810:Mice, Inbred C57BL; D014611:Vaccination
chemical_list: D001428:Bacterial Vaccines; D007371:Interferon-gamma