PRECLINICAL IMMUNOPROPHYLACTIC AND IMMUNOTHERAPEUTIC EFFICACY OF ANTISERA TO CAPSULAR POLYSACCHARIDE-TETANUS TOXOID CONJUGATE VACCINES OF VIBRIO-VULNIFICUS

Vibrio vulnificus is an oyster-associated bacterial pathogen that caus es life-threatening fulminating septicemia and necrotizing wound infec tions in humans. The capsular polysaccharide of V. vulnificus (VvPS) i s critical for virulence. Previously we showed that active immunizatio n of mice with a VvPS-tetanus toroid (VvPS-TTa) conjugate vaccine conf erred significantly higher protection against subsequent lethal challe nge than immunization with VvPS alone. In the current study, we examin ed the utility of immunoprophylaxis or immunotherapy with hyperimmune antisera elicited by VvPS-TTa and VvPS-TTb conjugate vaccines prepared by different synthetic schemes. First we demonstrated that the Ribi a djuvant significantly enhanced the murine antibody response (P less th an or equal to 0.02) to both conjugates. Subsequently, high-titered po lyclonal antisera were raised to VvPS-TTa and VvPS-TTb conjugate vacci nes by using Ribi adjuvant or Freund's adjuvants. Antisera were observ ed to have protective effects when administered before and after acute lethal infection. All animals receiving prophylactic antisera intrape ritoneally 24 h before lethal challenge with homologous carbotype 1 we re protected, while 73 to 100% of control mice succumbed. Immunotherap y was also effective, with survival rates of 60 to 73% seen among mice when antisera were administered 2 h after bacterial challenge, at a t ime when symptoms of infection were already apparent. The protective e ffect of capsular antiserum appeared to be serotype specific. Antisera to the carbotype 1 VvPS-TTa vaccine did not confer cross-protection a gainst lethal challenge with carbotype 2 V. vulnificus despite partial structural similarity and a weak serological cross-reaction between t he two carbotypes. Immune globulins induced by a potential multivalent VvPS conjugate vaccine composed of clinically prevalent carbotypes ma y have utility in the management of V. vulnificus infections and deser ve further evaluation.