Capsule conjugate vaccines against Campylobacter jejuni

描述(申请人提供)：空肠弯曲杆菌是一种B类细菌，是引起腹泻疾病的主要细菌之一，目前还没有疫苗可用。该项目的假设是胶囊结合疫苗可以预防空肠弯曲菌引起的腹泻疾病。我们已经开发了针对HS23、36血清组和HS4血清组两种胶囊类型的原型胶囊结合疫苗。这些疫苗是通过将每种血清型的纯化衣壳多糖与CRM197结合而合成的，CRM197是一种用于特许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作用。HS23、36疫苗在肌肉注射3剂(每剂25微克)后，也能保护南美姬鼠免受腹泻疾病的侵袭。基于这些结果，我们建议建立空肠弯曲菌81-176(HS23，36)株cGMP胶囊的制备方法，与CRM197接合，并对产品进行包装。该产品将在化学成分、安全性和免疫原性方面进行表征，以期提交IND进行第一阶段人体测试。

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.