A multivalent OMV vaccine induces broad protection against major Klebsiella pneumoniae disease-causing serotypes

The antigenic diversity of Klebsiella pneumoniae surface polysaccharides, O- and K-antigen, represents a significant challenge for developing broadly-acting vaccines. Here we report the development of Kp-OMV4, a multivalent outer membrane vesicle (OMV) vaccine incorporating the four predominant K. pneumoniae O-antigen serotypes responsible for most invasive disease worldwide. Kp-OMV4 elicits robust humoral and cellular immune responses, generating high-titer antibodies against both surface polysaccharides and conserved outer membrane proteins. Vaccine-induced antibodies display complement-mediated bactericidal activity against hypervirulent and multidrug-resistant clinical strains. In a murine sepsis model, immunization confers protection against lethal challenge and significantly reduces post-infection bacterial burden. Importantly, immune sera broadly recognize diverse clinical isolates, including strains expressing O- and K-antigen serotypes not included in the vaccine, supporting potential for broad strain coverage. This study indicates that the multicomponent nature of OMVs can be leveraged to overcome bacterial antigenic diversity and enable the development of vaccines with broad strain coverage. The authors report that a multivalent OMV vaccine against Klebsiella pneumoniae provides protection against lethal challenge with multiple strains in a mouse sepsis model, and induces antibodies that broadly recognize clinical isolates with diverse O- and K-antigen serotypes.