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: 6960345
• 负责人: STEPHEN B. CALDERWOOD
• 金额: $ 44.84万
• 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/6960345
• 关键词: B lymphocyte; Vibrio cholerae; bacterial proteins; bactericidal immunity; biopsy; biotechnology; blood tests; cholera; cholera vaccine; clinical research; cooperative study; disease /disorder prevention /control; feces analysis; gene expression; gene expression profiling; high throughput technology; human subject; human therapy evaluation; immune response; immunologic memory; longitudinal human study; microarray technology; mucosal immunity; proteomics; vaccine development; vaccine evaluation

DESCRIPTION (provided by applicant): This project is a collaboration between Massachusetts General Hospital-Harvard Medical School and the International Centre for Diarrheal Disease Research in Bangladesh (ICDDR,B), focused on defining protective 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, which generate immune responses that are protective on subsequent exposure; an ancillary hypothesis is that these proteins are not adequately expressed during colonization with available vaccine strains, and that these differences may explain the lessened efficacy of current vaccines. There are five specific aims in this project. In Specific Aim 1, the investigators will determine the genes and proteins expressed during human infection with V. cholerae in Bangladesh, utilizing gene expression profiling by microarray in samples of stool and vomit, as well as proteomic analysis 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 immune responses. In Specific Aim 3, the investigators will assess the duration of immunity to key cholera antigens following both cholera and Peru-15 vaccination over a 1-year followup period. The duration of immunity will be evaluated in serum, feces, and duodenal biopsies, as well as with a newly described methodology for measuring circulating, antigen-specific memory B cells. In Specific Aim 4, the investigators will examine which of the immune responses to in vivo-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 3 immunologic responses (as a marker of an anamnestic response), and the number of circulating, antigen-specific memory B cells at baseline. In Specific Aim 5, the investigators will evaluate selected host factors for correlation with development of immune responses following cholera 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 develop the theoretical underpinnings for an improved vaccine for prevention of cholera, and to accomplish substantial technology transfer and capacity building at the ICDDR,B.

DESCRIPTION (provided by applicant): This project is a collaboration between Massachusetts General Hospital-Harvard Medical School and the International Centre for Diarrheal Disease Research in Bangladesh (ICDDR,B), focused on defining protective 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, which generate immune responses that are protective on subsequent exposure; an ancillary hypothesis is that these proteins are not adequately expressed during colonization with available vaccine strains, and that these differences may explain the lessened efficacy of current vaccines.该项目有五个具体目标。 In Specific Aim 1, the investigators will determine the genes and proteins expressed during human infection with V. cholerae in Bangladesh, utilizing gene expression profiling by microarray in samples of stool and vomit, as well as proteomic analysis 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 immune responses. In Specific Aim 3, the investigators will assess the duration of immunity to key cholera antigens following both cholera and Peru-15 vaccination over a 1-year followup period. The duration of immunity will be evaluated in serum, feces, and duodenal biopsies, as well as with a newly described methodology for measuring circulating, antigen-specific memory B cells. In Specific Aim 4, the investigators will examine which of the immune responses to in vivo-expressed proteins are protective following exposure to V. cholerae in household contacts utilizing: baseline antibody liters to key antigens in serum and feces;基线到第3天免疫反应的增加（作为吞咽反应的标记），以及基线时循环，抗原特异性记忆B细胞的数量。 In Specific Aim 5, the investigators will evaluate selected host factors for correlation with development of immune responses following cholera or Peru-15 vaccination, as well as with susceptibility to symptomatic cholera following exposure in household contacts.该项目的长期目标是开发用于预防霍乱的改进疫苗的理论基础，并在ICDDR，b。