Zeolitic Imidazole Framework-8 Nanoparticles as an Alternative to Freund's Adjuvant for Klebsiella pneumoniae Recombinant Protein Vaccine

Abstract

Vaccination represents a promising approach to combat resistant Klebsiella pneumoniae (KP). However, there is currently no licensed vaccine in the veterinary field. Outer membrane proteins have been proven to possess good immunogenicity, but Freund's adjuvant, which is commonly used to administer protein vaccines, has limitations such as a complicated formulation process as well as a tendency to cause pain and inflammation in animals. Here, we prepared a nano-vaccine based on zeolitic imidazolate framework-8 (ZIF-8)-encapsulated outer membrane protein PhoE and evaluated its efficiency in enhancing humoral and cellular immune responses in BALB/c mice. ZIF-8 nanoparticles rapidly delivered the protein antigen into dendritic cells and successfully activated them. In addition, significantly higher IgG antibody titers, cytokine levels, and splenocyte proliferation indices were founded in mice subcutaneously immunized with PhoE@ZIF-8 than in those receiving free PhoE alone. In a BALB/c mouse model, PhoE@ZIF-8 elicited a strong immune response with improved prophylactic efficacy against KP that was similar to the Freund's adjuvant-formulated vaccine. Based on the superiority of this nano-vaccine with good biocompatibility, inexpensive preparation and higher efficiency of delivering antigen into cells, ZIF-8 can serve as a promising replacement for Freund's adjuvant in research, with a prospective usage for vaccines against bacterial pathogens in the veterinary field.