CAPSULAR POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES OF VIBRIO VULNIFICUS

创伤弧菌引起致命的败血症和伤口感染

Vibrio vulnificus causes fatal septicemic and wound infections in immunocompromised and normal humans. The capsular polysaccharide of V. vulnificus (VvPS) is critical for virulence. Previously, we developed a variety of conjugate vaccines by conjugating VvPS to tetanus toxoid (TT), and cytolysin and elastase of V. vulnificus and evaluated their protective efficacy following active immunization. We have now evaluated the immunoprophylactic and immunotherapeutic efficacy of murine and rabbit hyperimmune antisera, prepared using VvPS-TTa and VvPS-TTb conjugates, in a murine model. Total protection (100%) was conferred by VvPS-TT conjugate-induced antisera when administered 24 hours before lethal challenge with homologous carbotype of V. Vulnificus, and 60-73% protection was observed in mice which were treated with the antisera 2 hours after lethal infection, at a stage when the symptoms of sickness were quite apparent. There was 67-100% mortality among control mice injected with normal serum or with antisera to irrelevant polysaccharides or proteins. This reversal of disease course elicited by conjugate-induced antisera is most relevant to a human setting, particularly in patients who get admitted with advanced infection with a very short window of time available to the physicians to treat. Given the high mortality rate in humans of 55-79% despite aggressive antibiotic and supportive therapy, and the rapid progression of septicemia to death (24-48 h), the results of passive protection experiments become highly significant and clinically relevant. The results suggest the feasibility of using VvPS conjugate-induced hyper immune globulins in the immunoprophylaxis of high risk populations and immunotherapy in the clinical management of patients with V. vulnificus septicemia.