Capsule conjugate vaccines against Campylobacter jejuni

描述（由申请人提供）：空肠弯曲杆菌是B类病原体，是引起腹泻疾病的主要细菌之一，目前尚无疫苗。本课题假设胶囊结合疫苗可预防空肠弯曲杆菌引起的腹泻病。我们已经开发了针对两种胶囊类型的原型胶囊结合疫苗，即hs2336血清组和HS4血清组。这些疫苗是通过将纯化的每种血清型荚膜多糖与CRM197结合合成的，CRM197是一种用于已获许可的cps结合疫苗的白喉类毒素。在小鼠鼻内感染模型中，这两种疫苗都显示出对疾病的显著保护。在肌肉注射三剂（每次25微克）hs23,36疫苗后，也可保护南腹小腹鼠免受腹泻疾病。在此基础上，我们提出了空肠梭菌81-176 （hs23,36）荚膜的cGMP制备、与CRM197的偶联以及产品的装瓶方法。该产品将在化学成分、安全性和免疫原性方面进行表征，预计将提交IND进行1期人体试验。

DESCRIPTION (provided by applicant): Campylobacter jejuni is a Category B agent that is one of the major bacterial causes of diarrheal disease, and there are no vaccines available. The hypothesis of this project is that capsule conjugate vaccines can protect against diarrheal disease caused by Campylobacter jejuni. We have developed prototype capsule conjugate vaccines against two capsule types, that of the HS23, 36 serogroup and that of the HS4 serogroup. These vaccines were synthesized by conjugation of purified capsular polysaccharide of each serotype to CRM197, a diptheria toxoid used in licensed CPS-conjugate vaccines. Both of these vaccines showed significant protection against disease in a mouse intra-nasal model of infection. The HS23, 36 vaccine was also protected Aotus nancymae from diarrheal disease following 3 doses (25 micrograms each) administered intramuscularly. Based on these results we propose to develop methods for cGMP manufacture of the capsule from C. jejuni strain 81-176 (HS23, 36), conjugation to CRM197, and vialing of the product. The product would be characterized for chemical composition, safety, and immunogenicity in anticipation of IND submission for phase 1 human testing.