Novel and MAPS vaccine combining O polysaccharides and pathogen-specific proteins.

(KP) and (PA) are leading causes of healthcare-associated and community-acquired infections. Despite decades of efforts, there are no licensed vaccines for either pathogen. The surface O polysaccharides (OPS) of and are essential virulence factors for these bacteria and are targets of protective antibacterial antibodies. The multiple antigen presenting system (MAPS) vaccine platform was used to create a multivalent / vaccine in which the surface OPS of four and eight strains were linked to a high MW biotinylated (KO) K19 capsular polysaccharide backbone and subsequently linked to pathogen-specific fusion proteins, consisting of MrkA, the flagellin B D2 subunit, and PcrV. We show here that these MAPS complexes incorporating KP and PA OPS, as well as pathogen-specific proteins, were highly immunogenic in rabbits and mice and induced functionally active antibodies and in murine animal models.IMPORTANCEInfections caused by (KP) and (PA) are widely recognized to be of "urgent" and "serious" concern, in part because of their widespread antimicrobial resistance. To date, there is no licensed vaccine for either pathogen. We developed a novel multiple antigen presenting system (MAPS) vaccine platform that contains eight O polysaccharides (OPS) of PA and four OPS of KP, which will cover over 80% of clinical infections with these pathogens. In addition, this vaccine includes three pathogen-relevant proteins acting both as carrier proteins to provide T cell help for these polysaccharides as well as to elicit functionally active antibodies that may also protect against KP and PA infection. The use of pathogen-relevant proteins that may contribute to vaccine efficacy in place of the more traditional carrier proteins is a novel concept. The MAPS vaccine platform also generates Th17 and Th1 responses. This KP/PA MAPS vaccine may prevent infection with these pathogens and reduce their transmissibility.