伤寒结合疫苗免疫原性和动物安全性研究

伤寒V i多糖与白喉类毒素(DT)蛋白以己二酰肼(ADH)作连接臂,在碳二亚胺(EDAC)的作用下结合成V i-DT结合物,进行抗原性、免疫原性和动物安全性试验。结果显示,3批结合物抗体阳转率均为100%,加强免疫一针后GMT值明显升高(p<0.001),免疫剂量以0.75μg/只抗体增长最为明显,甚至以低剂量0.375μg/只仍能获得较高的抗体滴度,多项动物试验证明该结合物是安全的。显示V i-DT结合物有很好的动物安全性和免疫原性,为临床试验提供实验室依据。

Immunogenicity and animal safety of Typhoid Vi conjugate vaccine

The Vi capsular polysaccharide of Salmonella typhi was bound to diphtheria toxoid(DT) with adipic acid dihydrazide(ADH) as a linker,and EDAC used as a condensating agent.The reaction mixture was passed through a Sephacryl S-1000 column(2.6 x 90 cm) along with a equilibrated saline,the pooled fractions from void volume were conjugates.The conjugates were analyzed and injected in mice and Guinea pigs to evaluate the immunogenicity and animal safety.Vi-DT conjugates still maintain the antigenicity of Vi and elicite high levels anti-Vi IgG in mice.The charecterstics of conjugates are in conformation with the requirements for toxicity tests,and they were safe in animal test.