Capsule conjugate vaccines against Campylobacter jejuni

空肠弯曲菌胶囊结合疫苗

• 批准号: 7645240
• 负责人: Patricia Guerry
• 金额: $ 30.98万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-03 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7645240
• 关键词: Aotus primate; Campylobacter jejuni; Categories; Chemicals; Conjugate Vaccines; Disease; Dose; Epithelial Cells; Fermentation; Gene Mutation; Haemophilus influenzae; Heating; Human; In Vitro; Infection; Intestines; Invaded; Licensing; Meningitis; Methods; Modeling; Mucous Membrane; Mus; Neisseria; Nose; Pathogenesis; Phase; Polysaccharides; Principal Investigator; Procedures; Role; Running; Safety; Salmonella; Scheme; Serotyping; Serum; Streptococcus Group B; Streptococcus pneumoniae; Testing; Toxicology; Toxoids; Vaccines; Virulence; base; capsule; cross reacting material 197; efficacy testing; immunogenicity; in vivo; manufacturing process development; nonhuman primate; pathogen; pre-clinical; protective efficacy; prototype; success; vaccine development

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.

描述（由申请人提供）：空肠弯曲杆菌是 B 类病原体，是腹泻病的主要细菌原因之一，并且没有可用的疫苗。该项目的假设是胶囊结合疫苗可以预防空肠弯曲杆菌引起的腹泻病。我们开发了针对两种胶囊类型的原型胶囊结合疫苗，即 HS23、36 血清群和 HS4 血清群。这些疫苗是通过将每种血清型的纯化荚膜多糖与 CRM197（一种用于许可的 CPS 结合疫苗中的白喉类毒素）结合而合成的。这两种疫苗在小鼠鼻内感染模型中显示出显着的预防疾病的作用。肌肉注射 3 剂（每剂 25 微克）后，HS23、36 疫苗还可以保护 Aotus nancymae 免受腹泻病的影响。基于这些结果，我们建议开发用于空肠弯曲菌菌株 81-176 (HS23, 36) 胶囊的 cGMP 制造方法、与 CRM197 缀合以及产品装瓶的方法。该产品将在化学成分、安全性和免疫原性方面进行表征，以期提交 IND 进行第一阶段人体测试。