KbvR mutant of Klebsiella pneumoniae affects the synthesis of type 1 fimbriae and provides protection to mice as a live attenuated vaccine

Abstract

Abstract Klebsiella pneumoniae is a leading cause of severe infections in humans and animals, and the emergence of multidrug-resistant strains highlights the need to develop effective vaccines for preventing such infections. Live attenuated vaccines are attractive vaccine candidates available in the veterinary field. We recently characterized that the K. pneumoniae kbvR (K lebsiella biofilm and virulence regulator) mutant was a highly attenuated strain in the mice model. In the present study, the characterization, safety, and protective efficacy of ΔkbvR strain as a live attenuated vaccine were evaluated. The synthesis and activity of type 1 fimbriae were increased in the ΔkbvR strain. All mice inoculated by the subcutaneous route with 105, 106, and 107 colony-forming units (CFU) doses of the ΔkbvR strain survived. Subcutaneous immunization with two doses of 105 or 107 CFU ΔkbvR elicited a robust humoral immune response, and provided protection against the following K. pneumoniae intraperitoneal infection. The antisera of mice immunized with 105 CFU dose improved the opsonophagocytic ability and complement-mediated lysis not only to the same serotype strain but also to the different serotype strain. The passive transfer of antisera from 105 CFU dose-immunized mice provided protection against K. pneumoniae infection. Overall, our results suggest the great potential of the ΔkbvR strain as a novel vaccine candidate against K. pneumoniae infections in herds or humans.

Keywords

• Klebsiella pneumoniae
• KbvR
• vaccine
• immune response