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 食用生蚝或暴露于 牡蛎捕捞水域的开放性伤口。冬虫夏草胶囊多糖的研究 创伤弧菌(VvPS)被认为具有 侵犯性。目的是评估致病和致病的 创伤弧菌VvPS等蛋白抗原的保护性作用 合成C1型VVPS与TT或灭活疫苗的结合疫苗 两种不同方案对创伤弧菌细胞溶血素或弹性蛋白酶的影响。这个 这些结合物在瑞士粪便小鼠中的免疫原性是通过 皮下注射生理盐水。所有的共轭引出了更高的 囊膜抗体反应优于VvPS单独和诱导升高的免疫球蛋白和 免疫球蛋白反应。通过羧基活化制备的偶联物 VVPS(VvPS-TTA、VvPS-溶细胞素和VvPS-弹性蛋白酶)具有更强的免疫原性 比通过羟基活化制备的产物(VvPS-TTB)更好。囊状 抗体反应显著增强的同时 结合物与MPL+TDM佐剂的腹腔注射。 VVPS、细胞溶血素和VVPS的单独和协同保护作用 弹性蛋白酶单独和结合疫苗形式在小鼠身上进行了评估 败血症模型。VVPS-TTA疫苗对80%的 小鼠腹腔感染-5LD50后的主动免疫 而VvPS所提供的保护作用- 细胞溶血素和VVPS-弹性蛋白酶分别为40%和44%。VVPS-TTB是 防护性最差。用VVPS、细胞溶血素或 单独使用弹性蛋白酶、VVPS和细胞溶血素，或仅使用生理盐水，显示70- 100%的死亡率。因此，VvPS-TTA具有高度的免疫原性和保护性。 小鼠，似乎适合于临床评估。无源保护 使用VvPS-TTA诱导的抗血清的研究正在进行中。

Vibrio vulnificus causes fatal septicemic and wound infections in immunocompromised humans following raw oyster consumption or exposure of open wounds to oyster-harvested waters. The capsular polysaccharide of Vibrio vulnificus (VvPS) is believed to confer the property of invasiveness. With the objective of evaluating the pathogenic and protective roles of VvPS and other protein antigens of V. vulnificus, we synthesized conjugate vaccines of carbotype 1 VvPS with TT or inactivated cytolysin or elastase of V. vulnificus by two different schemes. The immunogenicity of these conjugates was evaluated in Swiss shite mice by subcutaneous injections in saline. All conjugates elicited higher capsular antibody responses than VvPS alone and induced elevated IgG and IgM responses. The conjugates prepared through carboxyl activation of VvPS (VvPS-TTa, VvPS-cytolysin and VvPS-elastase) were more immunogenic than the one prepared through hydroxyl activation (VvPS-TTb). Capsular antibody response was significantly enhanced by concurrent intraperitoneal administration of conjugates with MPL+TDM adjuvant.The individual and synergistic protective effects of VvPS, cytolysin and elastase alone and in conjugate vaccine forms were evaluated in a mouse septicemia model. VvPS-TTa vaccine conferred protection to 80% of actively immunized mice following intraperitoneal infection with -5 LD50 of carbotype 1 V. vulnificus, while the protection conferred by VvPS- cytolysin and VvPS-elastase was 40 and 44% respectively. VvPS-TTb was least protective. Control mice immunized with VvPS, cytolysin or elastase alone, VvPS followed by cytolysin, or saline only, showed 70- 100% mortality. Thus, VvPS-TTa is highly immunogenic and protective in mice, and appears suitable for clinical evaluation. Passive protection studies using VvPS-TTa-induced antisera are underway.