Capsule conjugate vaccines against ETEC and Campylobacter

描述(由申请人提供)： 项目简介这项建议的假设是，通过将产肠毒素大肠杆菌(ETEC)的LTB与ETEC的主要衣壳类型的不同定居因子抗原(CFA或菌毛)结合，可以生产出针对ETEC和空肠弯曲菌的多价疫苗。空肠弯曲菌是一种罕见的肠道病原体，因为它会产生一种多糖壳。有证据表明，由与CRM197结合的空肠弯曲杆菌胶囊组成的疫苗对非人类灵长类动物(NHP)的腹泻疾病具有保护作用。CRM197是一种白喉类毒素，用于特许结合疫苗。也有证据表明，菌毛顶端粘附素在抗原性上的多样性低于主要菌毛亚基，对NHP和人类也具有保护作用。将这些ETEC蛋白连接到空肠弯曲菌胶囊上，为开发针对细菌性腹泻的两个主要原因的多价、广谱疫苗提供了一种新的途径。/项目叙述产肠毒素大肠杆菌(ETEC)和空肠弯曲杆菌(CJ)是全球腹泻疾病的主要原因。ETEC和CJ对西方旅行者和资源有限国家的幼儿都是严重威胁，而且这两种病毒都没有获得许可的疫苗。该项目将针对这两种病原体的两种新疫苗策略结合在一起，目标是开发一种广谱疫苗。CJ主要血清型的多糖胶囊将与抗原性不同的ETEC菌毛顶亚单位和不耐热肠毒素LTB的结合亚基结合。多种结合物可以组合成多价疫苗，对这两种病原体的主要抗原变体提供保护。 相关：产肠毒素大肠杆菌(ETEC)和空肠弯曲菌(CJ)是世界范围内腹泻疾病的主要原因。ETEC和CJ对西方旅行者和资源有限国家的幼儿都是严重威胁，而且这两种病毒都没有获得许可的疫苗。该项目将针对这两种病原体的两种新疫苗策略结合在一起，目标是开发一种广谱疫苗。CJ主要血清型的多糖胶囊将与抗原性不同的ETEC菌毛顶亚单位和不耐热肠毒素的结合亚单位结合， LTB。多种结合物可以组合成多价疫苗，对这两种病原体的主要抗原变体提供保护。

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.