Capsule conjugate vaccines against Campylobacter jejuni

描述（由申请方提供）：空肠弯曲菌是一种B类病原体，是导致腹泻的主要细菌之一，目前尚无疫苗可用。本项目的假设是，胶囊结合疫苗可以预防空肠弯曲菌引起的腹泻病。我们已经开发了针对两种胶囊类型的原型胶囊缀合物疫苗，即HS 23，36血清群的胶囊类型和HS 4血清群的胶囊类型。这些疫苗是通过将每种血清型的纯化荚膜多糖与CRM 197（一种用于许可的CPS偶联疫苗的白喉类毒素）偶联而合成的。这两种疫苗在小鼠鼻内感染模型中均显示出显著的抗疾病保护作用。HS 23，36疫苗在肌内注射3次（每次25微克）后也可保护南西对虾免受炭疽病的侵害。基于这些结果，我们建议开发从C.空肠菌株81-176（HS 23，36），与CRM 197接合，并将产物装瓶。该产品将表征化学成分、安全性和免疫原性，以预期IND提交用于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.