Capsule conjugate vaccines against ETEC and Campylobacter

针对 ETEC 和弯曲杆菌的胶囊结合疫苗

• 批准号: 8277111
• 负责人: Patricia Guerry
• 金额: $ 65.15万
• 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: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277111
• 关键词: Adhesives; Antibodies; Aotus primate; Bacterial Adhesins; Binding; Campylobacter; Campylobacter jejuni; Cattle; Child; Conjugate Vaccines; Country; Development; Diarrhea; Diphtheria Toxin; Diphtheria Toxoid; Disease; Drug Formulations; Enterotoxins; Escherichia coli Proteins; Heating; Human; Laboratories; Licensing; Modeling; Mus; Polysaccharides; Proteins; Recombinants; Resources; Serotyping; Vaccines; Variant; Virulence; Virulence Factors; base; capsule; colonization factor antigens; cross reacting material 197; efficacy testing; enteric pathogen; enterotoxigenic Escherichia coli; fimbria; immunogenic; immunogenicity; mutant; nonhuman primate; novel strategies; novel vaccines; pathogen; protective efficacy; volunteer

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.

描述（由申请人提供）： 项目描述 该提案的假设是，通过将 LTB 和来自 ETEC 的抗原性不同的定植因子抗原（CFA 或菌毛）与空肠弯曲杆菌的主要胶囊类型结合，可以产生针对产肠毒素大肠杆菌 (ETEC) 和空肠弯曲杆菌的多价疫苗。空肠弯曲菌对于肠道病原体来说是不常见的，因为它会产生多糖胶囊。有证据表明，由与 CRM197（一种用于许可结合疫苗的白喉类毒素）结合的空肠弯曲菌胶囊组成的疫苗可以预防非人类灵长类动物 (NHP) 的腹泻疾病。还有证据表明，菌毛尖端粘附素的抗原多样性低于主要菌毛亚基，但对 NHP 和人类也具有保护作用。将这些 ETEC 蛋白与空肠弯曲菌胶囊结合，为开发针对细菌性腹泻的两种主要原因的多价广谱疫苗提供了一种新方法。 /项目叙述产肠毒素大肠杆菌 (ETEC) 和空肠弯曲杆菌 (CJ) 是全世界腹泻病的主要原因。 ETEC 和 CJ 都对资源有限国家的西方旅行者和幼儿构成严重威胁，并且这两种病原体都没有获得许可的疫苗。该项目结合了针对这两种病原体的两种新型疫苗策略，旨在开发一种广谱疫苗。来自 CJ 主要血清型的多糖胶囊将与抗原性不同的 ETEC 菌毛尖端亚基和不耐热肠毒素 LTB 的结合亚基缀合。多种缀合物可以组合成多价疫苗，该疫苗可以针对两种病原体的主要抗原变体提供保护。 相关性：产肠毒素大肠杆菌 (ETEC) 和空肠弯曲杆菌 (CJ) 是全世界腹泻病的主要原因。 ETEC 和 CJ 都对资源有限国家的西方旅行者和幼儿构成严重威胁，并且这两种病原体都没有获得许可的疫苗。该项目结合了针对这两种病原体的两种新型疫苗策略，旨在开发一种广谱疫苗。 来自 CJ 主要血清型的多糖胶囊将与抗原性不同的 ETEC 菌毛尖端亚基和热不稳定肠毒素的结合亚基缀合， LTB。多种缀合物可以组合成多价疫苗，该疫苗可以针对两种病原体的主要抗原变体提供保护。