Natural infection of norovirus and sapovirus in a birth cohort in a Peruvian periurban community

项目摘要 产肠毒素大肠杆菌（ETEC）是腹泻的最常见原因，影响数百万人， 发展中国家的儿童。然而，ETEC在幼儿中的真正负担和 获得性免疫仍然知之甚少。不同地理区域的准确估计将 强调疫苗的公共卫生重要性，这些数据对于减少 减轻负担，促进疫苗开发。 成功开发疫苗的一个重大挑战是我们对免疫系统的理解不足。 这些反应与ETEC疾病的保护最相关。更好地理解 非免疫和免疫受试者对各种ETEC菌株的局部和血清应答之间的差异是 因为这些数据将为评价ETEC提供重要的免疫学基准， 疫苗和免疫方案。 我们建议将ETEC研究添加到NIH资助的诺如病毒新生儿队列研究中， 我们在利马城郊社区进行了儿童队列研究， 超过20年。通过利用这项研究，我们可以获得有关ETEC的信息， 这是一项独立研究。为了促进这项拟议的工作，我们正在与JHU ETEC研究合作， 团队，提供专业知识和最先进的技术来评估ETEC疾病， 自然获得的免疫力 与父母研究一样，我们将通过纵向社区队列跟踪婴儿，以充分了解 对一种在生命早期多次感染幼儿的疾病的天然免疫力。我们将解决 通过解决关键问题， 有效的疫苗设计和部署：我们将量化基因型特异性ETEC发生率， 发病率，我们将通过与宿主血型抗原， 分泌状态和血清、粪便和唾液中的ETEC抗原特异性抗体 疾病、感染和脱落。 具体目标1。通过进行纵向研究，描述秘鲁儿童中ETEC的流行病学特征 从出生到3岁的队列研究，包括系统收集数据和标本。 具体目标2。在一个子集中，评价在频繁暴露的情况下对ETEC的获得性保护性免疫 of cohort队列children儿童.

Project Summary Enterotoxigenic Escherichia coli (ETEC) are the most common cause of diarrhea, afflicting millions of children in the developing world. However, the true burden of ETEC in young children and the role of acquired immunity remains poorly understood. Accurate estimates in different geographic regions will highlight the public health importance of a vaccine, and these data are critically important to reduce the burden and to facilitate vaccine development. A significant challenge to successful vaccine development is our poor understanding of the immune responses that correlate best with protection against ETEC illness. A better understanding of the interplay between local and serum responses to various ETEC strains in non-immune and immune subjects is needed since these data will provide important immunological benchmarks for the evaluation of ETEC vaccines and immunization regimens in the future. We propose to add studies of ETEC to an already NIH-funded newborn cohort study of norovirus and sapovirus infection in a peri-urban Lima community, where we have conducted child cohort studies for more than 20 years. By leveraging this study, we can gain information about ETEC at a fraction of the cost were it a stand-alone study. To facilitate this proposed work, we are collaborating with a JHU ETEC research team, which provides access to expertise and state-of-the-art techniques to evaluate ETEC disease and naturally-acquired immunity. As in the parent study, we will follow the infants through a longitudinal community cohort to fully understand the natural immunity to a disease that infects young infants multiple times early in life. We will address the knowledge gap of ETEC epidemiology and immune response in young children by addressing issues key to effective vaccine design and deployment: we will quantify the genotype-specific ETEC incidence and morbidity, and we will evaluate acquisition of protective immunity by correlating host blood group antigen, secretor status, and ETEC antigen specific antibodies in serum, fecal matter, and saliva with ETEC disease, infection, and shedding. Specific Aim 1. Characterize the epidemiology of ETEC in Peruvian children by conducting a longitudinal cohort study from birth to age 3 years including systematic collection of data and specimens. Specific Aim 2. Evaluate acquired protective immunity to ETEC in a setting of frequent exposure in a subset of cohort children.