Effect of Oral Immunization with the Ty21a Typhoid Vaccine on Local and Systemic

Ty21a 伤寒疫苗口服免疫对局部和全身的影响

• 批准号: 7701564
• 负责人: CLAIRE M. FRASER
• 金额: $ 30.29万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-18 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7701564
• 关键词: Address; Adult; Animals; Antibiotic Resistance; Antibodies; Antibody Formation; Antigens; Attenuated; Attenuated Vaccines; Awareness; B-Lymphocytes; Bacteria; Biopsy; Blood; Blood Circulation; CD8B1 gene; Cells; Cellular Immunity; Child; Colonoscopy; Communities; Complex; Cytotoxic T-Lymphocytes; Developed Countries; Developing Countries; Development; Diagnostic; Disease; Distal part of ileum; Dose; Elderly; Feces; Gastrointestinal tract structure; Generations; Goals; Health; Homing; Human; Humoral Immunities; Immune response; Immunity; Immunization; Immunoglobulin-Secreting Cells; Individual; Infection; Knowledge; Licensing; Life; Longitudinal Studies; Measurement; Mediating; Memory; Memory B-Lymphocyte; Mononuclear; Mucosal Immunity; Mucous Membrane; Oral; Patients; Peripheral Blood Mononuclear Cell; Phase; Phase II Clinical Trials; Play; Population; Population Group; Production; Recombinants; Reporting; Role; Salmonella typhi; Sampling; Serum; Site; Specimen; Structure; T memory cell; Ty21a typhoid vaccine; Typhoid Fever; Typhoid Vaccine; Vaccinated; Vaccines; Work; cohort; cytokine; gut microbiota; improved; microbial community; microorganism; novel; older patient; oral vaccine; pathogen; prevent; public health priorities; rRNA Genes; response; young adult

The development of improved typhoid vaccines to prevent antibiotic-resistant typhoid fever in developing countries is a high global public health priority. The potential use of S. Typhi as a bioterror agent has added an additional reason to study this important global pathogen. The goal of this project is to characterize, at the mucosal and systemic levels, both short and long-term humoral and cell-mediated immunity (CMI) induced by oral immunization with the licensed attenuated S. Typhi Ty21a vaccine and to explore the interactions between Ty21a immunization and the gut microbiota. The development of improved live oral typhoid vaccines has been hampered by a lack of detailed information of the specific determinants of protective immunity to S. Typhi infection. Moreover, the effector and memory immune responses to S. Typhi in circulation and in the gut microenvironment have not been characterized. Since the gastrointestinal tract is the site of entry of S. Typhi, the presence of effective and sustained immune responses in the local microenvironment are likely to be pivotal in protection from infection. Results from studies in typhoid patients and vaccine trials with attenuated S. Typhi strains in adults suggest that antibodies (Ab) to common S. Typhi antigens appear to play a protective role against S. Typhi infection, however, it is not known if such Abs mediate protection or serve as a surrogate for the more dominant protective cellular mediated immunity (CMI) resulting in the elimination of this iritracellular S. Typhi. In spite of the fact that children stand to benefit the most from improved typhoid vaccines, only cursory information is available concerning serum Ab levels and, to our knowledge, there are no reports on the induction of antibody secreting cells (ASC), memory B cells (BM) or CMI in this group of individuals. The elderly represent another population group that is understudied in terms of the generation of immune responses to this oral vaccine, as no information is available concerning the induction of either Ab or CMI responses. The growing awareness of the importance of the gut microbiota in health and disease has also raised the question as to the influence of the complex community of microorganisms that inhabit the gastrointestinal tract in oral immunization and vice versa. Therefore, this application in addition to examining the immune response, will also examine the interactions between immune responses to Ty21a immunization and the gut microbiota in children, adults and the elderly. Overall this application addresses two important aspects of the development of immunity to S. Typhi.

发展中国家预防耐药伤寒的改良伤寒疫苗 国家是全球公共卫生的一个高度优先事项。对S.伤寒作为一种生物恐怖剂， 这是研究这种重要的全球病原体的另一个原因。该项目的目标是表征， 粘膜和全身水平，短期和长期体液和细胞介导的免疫（CMI）诱导 通过口服免疫接种许可的减毒S.伤寒Ty21a疫苗，并探讨相互作用 Ty21a免疫和肠道微生物群之间的关系。改良口服伤寒活菌的研制 由于缺乏保护性免疫的具体决定因素的详细信息， 免疫S。伤寒感染。此外，对S.中伤寒 循环和肠道微环境的特征还没有被描述。因为胃肠道是 S.伤寒，在局部存在有效和持续的免疫反应， 微环境可能是保护免受感染的关键。伤寒患者研究结果 和减毒沙门氏菌的疫苗试验。提示成人伤寒沙门氏菌的抗体（Ab）可能与伤寒沙门氏菌感染有关。伤寒 抗原似乎对S.伤寒感染，但是，它是不知道，如果这样的抗体 介导保护或作为更占优势的保护性细胞介导的免疫的替代物 (CMI)从而消除了这种非肠细胞S.伤寒尽管事实上，孩子们站在 从改进的伤寒疫苗中受益最大，但有关血清抗体的信息仅为粗略的 水平，并且据我们所知，没有关于诱导抗体分泌细胞（ASC）的报道， 记忆B细胞（BM）或CMI。老年人是另一个人口群体， 在对这种口服疫苗产生免疫反应方面， 关于Ab或CMI反应的诱导可用。越来越多的人意识到 肠道微生物群在健康和疾病中的作用也提出了一个问题， 在口服免疫中栖息在胃肠道中的微生物群落，反之亦然。 因此，该应用程序除了检查免疫反应外，还将检查 Ty21a免疫的免疫应答与儿童、成人和成年人的肠道微生物群之间的关系 老人总的来说，本申请涉及对S.伤寒