Humoral and adaptive immune responses study in Vibrio cholerae infection

霍乱弧菌感染的体液和适应性免疫反应研究

• 批准号: 9892049
• 负责人: Md Taufiqur Rahman Bhuiyan
• 金额: $ 7.18万
• 依托单位: INTERNATIONAL CTR/DIARRHOEAL DIS RES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-22 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892049
• 关键词: Address; Affect; Affinity; Agar; Anti-Bacterial Agents; Antibodies; Antibody Response; Antigens; Area; B-Lymphocytes; Bacterial Toxins; Bangladesh; Belief; Biological Assay; Biopsy Specimen; Blood specimen; Boston; Cells; Child; Cholera; Cholera Toxin; Cholera Vaccine; Cloning; Collaborations; Development; Disease; Duodenum; Educational process of instructing; Flow Cytometry; General Hospitals; Genetic Variation; Genomics; Goals; Grant; Helper-Inducer T-Lymphocyte; Human; Immune response; Immunity; Immunoglobulin A; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin M; Immunoglobulin Somatic Hypermutation; Immunoglobulin Switch Recombination; Immunoglobulins; Immunologic Techniques; Immunology; Individual; Infection; Institutes; International; Knowledge; Liquid substance; Lymphocyte; Manuscripts; Massachusetts; Measures; Mediating; Mediator of activation protein; Memory; Memory B-Lymphocyte; Mentorship; Microbiology; Microscopy; Molecular Biology; Mononuclear; Morbidity - disease rate; Mucous Membrane; O Antigens; Onset of illness; Oral; Patients; Phenotype; Plasma Cells; Plasmablast; Predisposition; Preparation; Production; Program Development; Property; Proteins; Proteomics; Research; Research Personnel; Research Training; Resources; Serum; Source; Surface; T-Lymphocyte; Techniques; Time; Training; Training Programs; Universities; Vaccination; Vaccines; Vibrio cholerae; Vibrio cholerae infection; Western Blotting; Work; adaptive immune response; antitoxin; career development; cell motility; data management; diarrheal disease; enteric pathogen; experience; falls; graduate student; innate immune pathways; international center; mortality; nano; novel; peripheral blood; programs; response; skills

PROJECT SUMMARY Cholera is a severe dehydrating disease caused by Vibrio cholerae. Unfortunately, we do not yet know what is the prime functional mediator of protection against cholera. This deficit has impacted development of cholera vaccines, with currently available cholera vaccines providing lower-level and shorter-term protection against cholera, especially in children, than that afforded by previous wild type disease. We and others have generated strong preliminary evidence that protective immunity against cholera is mediated by antibodies at the mucosal surface, and that V. cholerae O-specific polysaccharide (OSP) is the primary antigenic target. V. cholerae is a motile non-invasive enteropathogen with a single polar sheathed flagellum (covered by LPS/OSP). We hypothesize that differences in the follicular T cell immune response between vaccinees and infected cholera patients suppress the immune responses in vaccinees. In addition, we also hypothesize that these differences affect the development, maturation, and functionality of antibody responses against key Vibrio cholerae antigens, O-specific polysaccharide (OSP) and cholera toxin (CT). To address these hypotheses, we propose three specific aims. Aim #1: We will use flow cytometry of mononuclear cells isolated from patients with cholera to evaluate follicular T cells (TFH) in relation to infection at different days after onset of disease and following vaccination. Aim #2: We will use a novel nano- well approach to isolate single cholera antigen-specific cells by phenotypic characterization in duodenal biopsy specimens (and peripheral blood) of individuals recovering from cholera. We will clone the immunoglobulin chains from these recovered lymphocytes, including plasmablasts, plasma cells, and memory B cells, and we will evaluate cloned antibodies for functionality, as well as affinity maturation and somatic hyper-mutation; we will perform a similar analysis of blood samples of vaccinees. Aim #3: We will assess for the presence of V. cholerae agglutinating and anti-motility antibodies in patients with cholera, as well as in vaccinees. This work builds upon a highly-successful and ongoing international collaborative effort between researchers at the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh (icddr,b), the Massachusetts General Hospital- Harvard in Boston and Emory University, Atlanta, USA. The goal of this K43 Emerging Global Leader Career Development Program would be to strengthen the skills necessary to become an independent researcher/investigator in mucosal immunology in resource-limited settings.

项目概要 霍乱是由霍乱弧菌引起的严重脱水性疾病。不幸的是，我们还没有 了解预防霍乱的主要功能介质是什么。这一赤字影响了 霍乱疫苗的开发，目前可用的霍乱疫苗提供较低水平和 与以前的野生型相比，对霍乱的短期保护，尤其是对儿童的保护 疾病。我们和其他人已经产生了强有力的初步证据表明，针对 霍乱是由粘膜表面的抗体介导的，并且霍乱弧菌 O 特异性 多糖（OSP）是主要的抗原靶点。霍乱弧菌是一种能动的非侵入性病原体 具有单个极鞘鞭毛（被 LPS/OSP 覆盖）的肠道病原体。我们假设 疫苗接种者和感染霍乱患者之间滤泡 T 细胞免疫反应的差异 抑制接种者的免疫反应。此外，我们还假设这些 差异会影响针对关键抗体反应的发展、成熟和功能 霍乱弧菌抗原、O 特异性多糖 (OSP) 和霍乱毒素 (CT)。为了解决这些 假设，我们提出三个具体目标。目标#1：我们将使用流式细胞术检测单核细胞 从霍乱患者中分离出的细胞，用于评估滤泡 T 细胞 (TFH) 与感染的关系 发病后和疫苗接种后的不同天。目标#2：我们将使用一种新颖的纳米 通过表型表征分离单个霍乱抗原特异性细胞的良好方法 霍乱康复者的十二指肠活检标本（和外周血）。我们将 从这些回收的淋巴细胞中克隆免疫球蛋白链，包括浆母细胞、血浆 细胞和记忆 B 细胞，我们将评估克隆抗体的功能性和亲和力 成熟和体细胞超突变；我们将对血液样本进行类似的分析 接种疫苗者。目标#3：我们将评估是否存在霍乱弧菌凝集性和抗蠕动性 霍乱患者以及疫苗接种者体内的抗体。这项工作建立在非常成功的基础上 以及国际中心研究人员之间正在进行的国际合作努力 孟加拉国达卡腹泻病研究 (icddr,b)、马萨诸塞州总医院 - 波士顿哈佛大学和美国亚特兰大埃默里大学。 K43 新兴全球领导者的目标 职业发展计划将加强成为独立人士所需的技能 资源有限环境中粘膜免疫学的研究员/调查员。

项目成果

Seroprevalence of SARS-CoV-2 antibodies in Bangladesh related to novel coronavirus infection.

孟加拉国与新型冠状病毒感染相关的 SARS-CoV-2 抗体血清阳性率。

• 发表时间: 2022-03
• 作者: Bhuiyan, Taufiqur Rahman;Akhtar, Marjahan;Akter, Aklima;Khaton, Fatema;Rahman, Sadia Isfat Ara;Ferdous, Jannatul;Nazneen, Arifa;Sumon, Shariful Amin;Banik, Kajal C;Bablu, Arifur Rahman;Alamgir, A S M;Rahman, Mahbubur;Tony, Selim Reza;Hossain
• 通讯作者: Hossain

Developing and validating a modified enzyme linked immunosorbent assay method for detecting HEV IgG antibody from dried blood spot (DBS) samples in endemic settings.

开发并验证改良的酶联免疫吸附测定方法，用于从流行环境中的干血斑 (DBS) 样本中检测 HEV IgG 抗体。

• 发表时间: 2022-03
• 影响因子: 5.8
• 作者: Sultana, Rosy;Bhuiyan, Taufiqur Rahman;Sathi, Afsana Shirin;Sharmin, Salma;Yeasmin, Sharmina;Uddin, Muhammad Ikhtear;Bhuiyan, Md Saruar;Mannoor, Kaiissar;Karim, Muhammad Manjurul;Zaman, K;Qadri, Firdausi
• 通讯作者: Qadri, Firdausi

Augmented immune responses to a booster dose of oral cholera vaccine in Bangladeshi children less than 5 years of age: Revaccination after an interval of over three years of primary vaccination with a single dose of vaccine.

5 岁以下孟加拉国儿童对口服霍乱疫苗加强剂量的增强免疫反应：在初次接种单剂疫苗三年以上后重新接种。

• 发表时间: 2020
• 影响因子: 5.5
• 作者: Chowdhury, Fahima;Bhuiyan, Taufiqur Rahman;Akter, Afroza;Bhuiyan, Md Saruar;Khan, Ashraful Islam;Tauheed, Imam;Ahmed, Tasnuva;Ferdous, Jannatul;Dash, Pinki;Basher, Salima Raiyan;Hakim, Al;Lynch, Julia;Kim, Jerome H;Excler, Jean;Kim, De
• 通讯作者: Kim, De

A non-inferiority trial comparing two killed, whole cell, oral cholera vaccines (Cholvax vs. Shanchol) in Dhaka, Bangladesh.

在孟加拉国达卡进行的一项非劣效性试验，比较了两种灭活全细胞口服霍乱疫苗（Cholvax 与 Shanchol）。

• 发表时间: 2022-01-28
• 影响因子: 5.5
• 作者: Chowdhury, Fahima;Akter, Afroza;Bhuiyan, Taufiqur Rahman;Tauheed, Imam;Teshome, Samuel;Sil, Arijit;Park, Ju Yeon;Chon, Yun;Ferdous, Jannatul;Basher, Salima Raiyan;Ahmed, Faez;Karim, Mahbubul;Ahasan, Mohammad Mainul;Mia, Masudur Rahman;Masud
• 通讯作者: Masud

Assessment of disease specific immune responses in enteric diseases using dried blood spot (DBS).

使用干血斑 (DBS) 评估肠道疾病的疾病特异性免疫反应。

• 发表时间: 2019
• 影响因子: 3.7
• 作者: Bhuiyan, Md Saruar;Hossain, Motaher;Sharmin, Salma;Shirin, Afsana;Khanam, Farhana;Chowdhury, Fahima;Akter, Afroza;Khan, Ashraful Islam;Uddin, Muhammad Ikhtear;Bhuiyan, Taufiqur Rahman;Qadri, Firdausi
• 通讯作者: Qadri, Firdausi