CAPSULAR POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES OF CARBOTYPE-1 VIBRIO-VULNIFICUS - CONSTRUCTION, IMMUNOGENICITY, AND PROTECTIVE EFFICACYIN A MURINE MODEL

Vibrio vulnificus causes septicemia and wound infections in immunocomp romised humans. The capsular polysaccharide of Vibrio vulnificus (VvPS ) is critical for virulence. We synthesized conjugate vaccines of carb otype 1 VvPS under conditions and in formulations suitable for human u se. Purified VvPS was conjugated to tetanus toroid (TT) or to inactiva ted V. vulnificus cytolysin or elastase by two different schemes. All conjugates elicited elevated anticapsular immunoglobulin G (IgG) and I gM and antiprotein IgG responses in mice compared with saline placebo. The conjugates prepared through carboxyl activation of VvPS (VvPS-TTa , VvPS-cytolysin, acid VvPS-elastase) were more immunogenic than the o ne prepared through hydroxyl activation (VvPS-TTb). The protective eff icacy of conjugated and unconjugated formulations of VvPS and that of protein carriers were evaluated in a mouse septicemia model. Eighty pe rcent of mice actively immunized with VvPS-TTa vaccine survived challe nge with carbotype 1 V. vulnificus, while VvPS cytolysin and VvPS-elas tase conjugates conferred 44 and 40% protection, respectively. Control mice immunized with VvPS, cytolysin, or elastase alone, or saline onl y, showed 70 to 100% mortality. VvPS-TTa vaccine is nontoxic, immunoge nic, and protective in mice.