Protective Immunity to Human Cholera in Bangladesh

孟加拉国对人类霍乱的保护性免疫力

• 批准号: 7451366
• 负责人: STEPHEN B. CALDERWOOD
• 金额: $ 8.39万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-05 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7451366
• 关键词: Age; Antibodies; Antibody Formation; Antigens; B-Lymphocytes; Bangladesh; Biopsy; Blood; Blood typing procedure; Cells; Cholera; Cholera Toxin; Cholera Vaccine; Clinical; Collaborations; Condition; Development; Diarrhea; Disease; Enrollment; Exposure to; Feces; Fimbriae Proteins; Funding; Gene Expression; Gene Expression Profiling; Gene Proteins; General Hospitals; Genes; Goals; Half-Life; Household; Human; Immune response; Immunity; Immunoglobulin-Secreting Cells; Immunologic Memory; In Vitro; Infection; Integration Host Factors; Longevity; Massachusetts; Measurement; Measures; Memory B-Lymphocyte; Messenger RNA; Methodology; Mucosal Immune Responses; Numbers; Nutritional status; Oral; Organism; Patients; Peru; Predisposition; Prevention; Proteins; Proteomics; Range; Research; Research Personnel; Sampling; Serum; Techniques; Tissues; Vaccination; Vaccines; Vibrio cholerae; Virulence Factors; Vitamin A; Vomiting; Week; Zinc; base; blood group; day; follow-up; immunogenic; improved; in vivo; international center; lipopolysaccharide B; medical schools; programs; response; sex

This project is a collaboration between Massachusetts General Hospital-Harvard Medical School andthe International Centre for Diarrhoeal Disease Research in Bangladesh (ICDDR,B), focused on definingprotective immunity to V. cholerae infection and developing an improved cholera vaccine. The central hypothesis of this project is that V. cholerae expresses specific proteins during early infection, whichgenerate immuneresponses that are protective on subsequent exposure; an ancillary hypothesis is that these proteins are not adequately expressed duringcolonization with available vaccine strains, and that these differences may explain the lessened efficacy of currentvaccines. There are five specific aims in this project. In Specific Aim #1, the investigators will determine the genes and proteins expressed during humaninfection with V. cholerae in Bangladesh, utilizing gene expression profiling by microarray in samples of stool and vomit, as well as proteomicanalysis of these samples. In Specific Aim #2, the investigators will identify proteins that are immunogenic following human infection with V.cholerae, as well as following vaccination with cholera vaccine strain Peru-15, in order to determine whether differences in gene expression between wild-type V.cholerae and Peru-15 may be correlated with differences in specific immuneresponses. In Specific Aim #3, the investigators will assess the durationof immunity to key cholera antigens followingboth cholera and Peru-15 vaccination over a one year follow-up period. Theduration of immunity will be evaluated in serum, feces, and duodenal biopsies, as well as with a newlydescribed methodology for measuring circulating, antigen-specific memoryB cells. In Specific Aim #4, the investigators will examine which of the immune responses to in v/vo-expressed proteins are protective following exposure to V.cholerae in household contacts utilizing: baseline antibody liters to key antigens in serum and feces; the increase in baseline to day 3immunologic responses (as a markerof an anamnestic response), and the numberof circulating, antigen-specific memoryB cells at baseline. In Specific Aim #5, the investigators will evaluate selected host factors for correlation with development of immune responses followingcholera or Peru-15 vaccination, as well as with susceptibility to symptomatic cholera following exposure in household contacts. The long term goals of this project are to developthe theoretical underpinnings for an improved vaccine for prevention of cholera, and to accomplish substantial technologytransfer and capacity building at the ICDDR.B.

该项目是马萨诸塞州总医院-哈佛医学院和国际 孟加拉国腹泻病研究中心（ICDDR，B），专注于确定对霍乱弧菌的保护性免疫 感染和开发改进的霍乱疫苗。该项目的中心假设是，霍乱弧菌表达 在早期感染过程中产生免疫反应的特异性蛋白质，在随后的暴露中具有保护作用; 辅助假设是这些蛋白质在可用疫苗株定殖期间没有充分表达， 这些差异可能解释了当前疫苗效力的降低。其中有五个具体目标 项目在具体目标#1中，研究人员将确定人类感染过程中表达的基因和蛋白质。 与孟加拉国的霍乱弧菌，利用粪便和呕吐物样本中的微阵列基因表达谱，以及 as proteomic蛋白质组analysis分析of these samples样品.在具体目标#2中，研究人员将鉴定具有免疫原性的蛋白质 在人感染霍乱弧菌后，以及在用霍乱疫苗株秘鲁-15接种后， 为了确定野生型霍乱弧菌和秘鲁-15之间的基因表达差异是否可能与 with differences差异in specific特定immuneresponses免疫responses反应.在具体目标#3中，研究人员将评估免疫力的持续时间 霍乱和秘鲁-15疫苗接种后一年的随访期内，Theduration 免疫力将在血清、粪便和十二指肠活检中进行评估，以及采用新描述的方法， 测量循环中抗原特异性记忆B细胞在具体目标#4中，研究人员将检查哪些 在家庭接触者中暴露于霍乱弧菌后，对体内表达蛋白的免疫应答具有保护性 利用：血清和粪便中关键抗原的基线抗体升数;基线至第3天免疫学指标的增加 反应（作为记忆反应的标志），以及循环中抗原特异性记忆B细胞的数量， 基线。在具体目标#5中，研究人员将评估选定的宿主因素与以下发展的相关性： 霍乱或秘鲁-15疫苗接种后的免疫应答，以及对症状性霍乱的易感性 在家庭接触后。该项目的长期目标是发展理论 为预防霍乱的改进疫苗奠定基础，并实现实质性技术转让 和能力建设。