Devi S J, Hayat U, Frasch C E, Kreger A S, Morris J G
Division of Bacterial Products, U.S. Food and Drug Administration, Bethesda, Maryland 20892, USA.
Infect Immun. 1995 Aug;63(8):2906-11. doi: 10.1128/iai.63.8.2906-2911.1995.
Vibrio vulnificus causes septicemia and wound infections in immunocompromised humans. The capsular polysaccharide of Vibrio vulnificus (VvPS) is critical for virulence. We synthesized conjugate vaccines of carbotype 1 VvPS under conditions and in formulations suitable for human use. Purified VvPS was conjugated to tetanus toxoid (TT) or to inactivated V. vulnificus cytolysin or elastase by two different schemes. All conjugates elicited elevated anticapsular immunoglobulin G (IgG) and IgM and antiprotein IgG responses in mice compared with saline placebo. The conjugates prepared through caboxyl activation of VvPS (VvPS-TTa, VvPS-cytolysin, and VvPS-elastase) were more immunogenic than the one prepared through hydroxyl activation (VvPS-TTb). The protective efficacy of conjugated and unconjugated formulations of VvPS and that of protein carriers were evaluated in a mouse septicemia model. Eighty percent of mice actively immunized with VvPS-TTa vaccine survived challenge with carbotype 1 V. vulnificus, while VvPS-cytolysin and VvPS-elastase conjugates conferred 44 and 40% protection, respectively. Control mice immunized with VvPS, cytolysin, or elastase alone, or saline only, showed 70 to 100% mortality. VvPS-TTa vaccine is nontoxic, immunogenic, and protective in mice.
创伤弧菌可导致免疫功能低下的人发生败血症和伤口感染。创伤弧菌的荚膜多糖（VvPS）对其毒力至关重要。我们在适合人类使用的条件和配方下合成了1型VvPS的结合疫苗。通过两种不同的方案将纯化的VvPS与破伤风类毒素（TT）或灭活的创伤弧菌溶细胞素或弹性蛋白酶偶联。与生理盐水安慰剂相比，所有偶联物在小鼠中均引发了更高的抗荚膜免疫球蛋白G（IgG）、IgM和抗蛋白IgG反应。通过VvPS的羧基活化制备的偶联物（VvPS-TTa、VvPS-溶细胞素和VvPS-弹性蛋白酶）比通过羟基活化制备的偶联物（VvPS-TTb）更具免疫原性。在小鼠败血症模型中评估了VvPS的偶联和未偶联制剂以及蛋白载体的保护效力。用VvPS-TTa疫苗主动免疫的小鼠中有80%在受到1型创伤弧菌攻击后存活，而VvPS-溶细胞素和VvPS-弹性蛋白酶偶联物分别提供了44%和40%的保护。单独用VvPS、溶细胞素或弹性蛋白酶或仅用生理盐水免疫的对照小鼠死亡率为70%至100%。VvPS-TTa疫苗在小鼠中无毒、具有免疫原性且有保护作用。
