Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity

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. Vaccines: Drawing protection from bacterial weaponry Tiny bundles of bacterial proteins stimulate immune protection against a pathogen responsible for pneumonia and other diseases. Klebsiella pneumoniae infection can be lethal in hospital settings and in immune-compromised individuals, and emerging antibiotic-resistant strains have further increased the danger of such infections. K. pneumoniae produces extracellular vesicles (EVs), tiny membrane bubbles coated with a variety of bacterial proteins, to facilitate infection. Researchers led by Seong Gyu Jeon at AEON Medix in South Korea found that these EVs can also elicit a potent and broad immune response in mice. Infections that were otherwise lethal to mice could be thwarted, with 80-100% of the animals surviving, depending on the dose of EVs received. These findings raise hopes that EV-based vaccines might offer similar protection for human patients.