Understanding the impact of Klebsiella pneumoniae K-Antigen based MAPS vaccine design on the immune response in animal models.

MAPS technology represents an innovative approach for the development of polysaccharide-based vaccines, relying on the affinity interaction between biotin and rhizavidin (rhavi), with potential for enhanced coverage through the incorporation of pathogen-specific proteins. Due to its flexibility, this platform is particularly attractive for the development of multivalent vaccines, as it is required for Klebsiella pneumoniae, a multidrug-resistant bacterium highlighted as prevalent cause of neonatal sepsis in low- and middle-income countries, against which no vaccines are currently available. In this work MrkA, a potential protective pathogen-specific protein antigen, was combined in a MAPS complex with K2 as model for Klebsiella K-antigen. The impact of sugar chain length, protein to polysaccharide ratio, and MAPS complex size on the immune response elicited in animal models was evaluated. Results showed that longer polysaccharides and higher protein/K-antigen ratios enhanced the immunogenicity in rabbits. Different proteins, i.e., rhavi alone and CP1-rhavi from Streptococcus pneumoniae, were also evaluated as carrier, showing that the protein antigen fused to rhavi can play a significant role on the resulting MAPS polysaccharide specific immunogenicity. Passive transfer of rabbit polyclonal sera from the most immunogenic MAPS complex was able to protect mice from challenge with a K2 clinical isolate. This work supports the rational design of a K-antigen MAPS-based vaccine against Klebsiella pneumoniae.