Mucosal immune response to oral cholera vaccine Peru 15

口服霍乱疫苗的粘膜免疫反应 秘鲁 15

• 批准号: 7093081
• 负责人: Firdausi Qadri
• 金额: $ 5.27万
• 依托单位: INTERNATIONAL CTR/DIARRHOEAL DIS RES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7093081
• 关键词: Bangladesh; Vibrio cholerae; active immunization; antigen antibody reaction; attenuated microorganism; bacterial antigens; bacterial proteins; bioterrorism /chemical warfare; cholera; cholera toxin; cholera vaccine; clinical trial phase I; clinical trial phase II; human tissue; immunologic assay /test; intestinal mucosa; lipopolysaccharides; live vaccine; lymphocyte; mucosal immunity; serum

DESCRIPTION (provided by applicant): The search for a protective vaccine against cholera suitable not only for adults but also for children and infants in developing countries is urgently needed. To address this issue, we have recently started a Phase I/II study of a live attenuated oral Vibrio cholerae O1 vaccine, Peru 15, in Bangladesh. In the ongoing trial, we are studying the safety and immunogenicity of Peru15 and are evaluating a few key immune responses: the vibriocidal response, and serum responses to the O1 lipopolysaccharide and cholera toxin. However, funds do not permit analysis of immune responses to other key antigens identified as part of our ongoing collaborative project under the International Collaborations in Infectious Disease Research (ICIDR) Program, focussed on determining the components of protective immunity to cholera. In this proposal, we have three SPECIFIC AIMS. In SPECIFIC AIM #1, we will determine serum mucosal immune responses to a key colonization factor of V. cholerae, TcpA, induced after immunization with Peru 15. In SPECIFIC AIM #2, we will use the antibody in lymphocyte supernatant or ALS assay to determine mucosal immune responses to LPS, CT and TcpA in the vaccinees. In SPECIFIC AIM #3, we will compare the serum and mucosal immune responses generated after vaccination with Peru15, to those occurring after natural cholera infection, measured in our ongoing ICIDR project. All of the assays will use samples already being obtained from Bangladeshi adults, children and infants in both the vaccine trial of Peru 15, as well as in our ongoing ICIDR project, so no new sample collection or human studies approvals will be needed. These studies will fill a key gap in the current evaluation of Peru15 by allowing the determination of key additional immune responses in vaccinees and comparison of those to individuals naturally infected with V. cholerae.

描述（由申请人提供）：迫切需要寻找针对霍乱的保护性疫苗，不仅适合成人，而且适合发展中国家的儿童和婴儿。为了解决这个问题，我们最近开始了孟加拉国的秘鲁15号疾病霍乱霍乱O1疫苗的I/II期研究。在正在进行的试验中，我们正在研究Peru15的安全性和免疫原性，并评估了一些关键的免疫反应：颤动的反应以及对O1脂多糖和霍乱毒素的血清反应。但是，资金不允许分析针对我们正在进行的合作项目一部分的其他关键抗原的免疫反应，这是在国际传染病研究（ICIDR）计划下进行的，重点是确定对霍乱的保护性免疫的组成部分。在此提案中，我们有三个具体的目标。在特定的目标＃1中，我们将确定对用秘鲁15进行免疫后诱导的霍乱葡萄球菌，TCPA的关键定植因子的血清粘膜免疫反应。在特定的目标＃2中，我们将在淋巴细胞上清液中使用抗体或ALS分析中的抗体来确定对LPS，ctCPA和TCPA的粘膜免疫反应。在特定的目标＃3中，我们将比较疫苗接种后与佩鲁15产生的血清和粘膜免疫反应与我们正在进行的ICIDR项目中自然霍乱感染后发生的患者进行比较。所有的测定方法将使用秘鲁15疫苗试验中的孟加拉国成年人，儿童和婴儿已经获得的样品，以及在我们正在进行的ICIDR项目中，因此不需要新的样本收集或人类研究批准。这些研究将通过确定疫苗中的关键额外免疫反应并将与自然感染的霍乱葡萄球菌感染的人进行比较，从而填补当前对Peru15评估的关键差距。