Capsule conjugate vaccines against ETEC and Campylobacter

描述（由申请人提供）： 项目描述本提案的假设是，通过将LTB和来自ETEC的抗原性不同的定殖因子抗原（CFA或菌毛）与C的主要荚膜类型结合，可以产生针对肠致病性大肠杆菌（ETEC）和空肠弯曲杆菌的多价疫苗。空肠。C.空肠对于肠道病原体是不寻常的，因为它产生多糖荚膜。有证据表明，由C.与CRM197（一种用于许可的缀合物疫苗中的白喉类毒素）缀合的空肠胶囊在非人灵长类动物（NHP）中具有针对霍乱的保护性。还有证据表明，菌毛尖端粘附素，其抗原多样性低于主要的菌毛亚基，在NHP和人类中也具有保护性。这些ETEC蛋白与C.空肠胶囊为开发针对细菌性腹泻的两个主要原因的多价、广谱疫苗提供了新的途径。肠源性大肠杆菌（ETEC）和空肠弯曲杆菌（CJ）是世界范围内导致腹泻的主要原因。ETEC和CJ都是对西方旅行者和资源有限国家的幼儿的严重威胁，并且没有针对这两种病原体的许可疫苗。该项目结合了针对这两种病原体的两种新型疫苗策略，旨在开发广谱疫苗。CJ主要血清型的多糖胶囊将与抗原性不同的ETEC菌毛尖端亚单位和热不稳定肠毒素LTB的结合亚单位结合。多种缀合物可以组合成多价疫苗，其将提供针对两种病原体的主要抗原变体的保护。 相关性：产肠毒素大肠杆菌（ETEC）和空肠弯曲杆菌（CJ）是全球腹泻病的主要原因。ETEC和CJ都是对西方旅行者和资源有限国家的幼儿的严重威胁，并且没有针对这两种病原体的许可疫苗。该项目结合了针对这两种病原体的两种新型疫苗策略，旨在开发广谱疫苗。 来自CJ主要血清型的多糖胶囊将与抗原性不同的ETEC菌毛尖端亚单位和热不稳定肠毒素的结合亚单位缀合， LTB。多种缀合物可以组合成多价疫苗，其将提供针对两种病原体的主要抗原变体的保护。

DESCRIPTION (provided by applicant): Project Description The hypothesis of this proposal is that multivalent vaccines can be generated against enterotoxigenic Escherichia coli (ETEC) and Campylobacter jejuni by conjugation of LTB and antigenically distinct colonization factor antigens (CFA's or fimbriae) from ETEC to the major capsule types of C. jejuni. C. jejuni is unusual for an enteric pathogen in that is produces a polysaccharide capsule. There is evidence that a vaccine consisting of a C. jejuni capsule conjugated to CRM197, a diphtheria toxoid used in licensed conjugate vaccines, was protective against diarrheal disease in non-human primates (NHP). Evidence also exists that fimbrial tip adhesins, which are less antigenically diverse than the major fimbrial subunits, are also protective in NHP's and humans. Conjugation of these ETEC proteins to C. jejuni capsules provides a novel approach to development of multivalent, broad-spectrum vaccines against two major causes of bacterial diarrhea. /project narrative Enterotoxigenic Escherichia coli (ETEC) and Campylobacter jejuni (CJ) are major causes of diarrheal disease worldwide. ETEC and CJ are both serious threats to western travelers and young children in resource limited countries, and there are no licensed vaccines available for either agent. This project combines two novel vaccine strategies against these two pathogens with the aim of a broad-spectrum vaccine. Polysaccharide capsules from major serotypes of CJ will be conjugated to antigenically distinct ETEC fimbrial tip subunits and the binding subunit of the heat labile enterotoxin, LTB. Multiple conjugates could be combined into a multi-valent vaccine that would afford protection against the major antigenic variants of both pathogens. Relevance: Enterotoxigenic Escherichia coli (ETEC) and Campylobacter jejuni (CJ) are major causes of diarrheal disease worldwide. ETEC and CJ are both serious threats to western travelers and young children in resource limited countries, and there are no licensed vaccines available for either agent. This project combines two novel vaccine strategies against these two pathogens with the aim of a broad-spectrum vaccine. Polysaccharide capsules from major serotypes of CJ will be conjugated to antigenically distinct ETEC fimbrial tip subunits and the binding subunit of the heat labile enterotoxin, LTB. Multiple conjugates could be combined into a multi-valent vaccine that would afford protection against the major antigenic variants of both pathogens.