Development of Mucosal and Systemic Immunity and Risk of Food Allergy

粘膜和系统免疫的发展以及食物过敏的风险

基本信息

批准号：
10265645
负责人：
Kirsi Jarvinen-Seppo
金额：
$ 24.52万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10265645
关键词：
16S ribosomal RNA sequencing Age-Months Allergens Allergic Allergic Disease Allergy to peanuts Animal Model Animals Antibiotics Antibodies Antibody Response Autoimmune Diseases B-Cell Development B-Lymphocyte Subsets B-Lymphocytes Bacteria Biological Markers Birth Cattle Child Childhood Childhood Asthma Clinical Clinical Trials Cohort Studies Consumption Data Defect Developed Countries Development Disease Eczema Environmental Risk Factor Exhibits Exposure to Extrinsic asthma Family Farming environment Feces Flow Cytometry Food Food Hypersensitivity Future Genomics Germ-Free Home Hypersensitivity IgE Immune Immune response Immune system Immunity Immunoglobulin A Immunoglobulin Class Switching Immunoglobulin G Immunoglobulin Variable Region Immunoglobulins Immunology Infant Infant Development Intervention Knowledge Learning Life Life Style Measures Memory B-Lymphocyte Mennonite Milk Mucosal Immunity Mucous Membrane Neonatal Oral Outcome Plasma Cells Play Population Predisposition Prevention Research Risk Role Saliva Secretory Immunoglobulin A Serum Somatic Mutation Sorting - Cell Movement Systems Development T-Lymphocyte Training Transcript Umbilical Cord Blood Vaginal delivery procedure animal data atopy base cohort design dietary early onset food allergen gut microbiome gut microbiota high risk high risk population immunogenic immunogenicity infancy microbial microbiome microorganism antigen mucosal site neonate peripheral blood postnatal prevent response support vector machine urban setting

项目摘要

Background: Transmission of the SARS-CoV-2 virus in human milk (HM) is unknown with only 11 poorly-described studies, reporting detectable virus in just 1 of the total 36 breastmilk samples. Further, it is possible that maternal SARS-CoV-2 infection during pregnancy and lactation confers some specific protection through antibodies. Only one study reports the presence of IgG to SARS-CoV-2 in HM. Alarming examples of antibody-dependent enhancement of other viral infections illustrate how critical it is to understand both the profile and activity of these antibodies in HM. It is critical then to understand the transmission risks and protective factors between mother and child through breastfeeding. Design: We propose a longitudinal cohort study of COVID-19+ mothers to determine risks of transmission (viral exposure of infants through breastfeeding by presence in HM and on areolar skin) and protective factors (SARS-CoV-2-specific antibody response in HM, profile and neutralization capacity) of breastfeeding. Longitudinal samples will allow us to assess temporal changes over disease course. Methods: We will enroll 50 COVID+ mothers in the first 3 months of lactation, 25 symptomatic and 25 asymptomatic. We will concurrently collect samples from two locations: The University of Rochester School of Medicine and Dentistry and New York University, NY. These sites will provide robust and staggered access to patients. We will recruit through local hospitals and social media platforms. Mothers will provide informed eConsent. IRB approval has been received. All samples will be self-collected in the hospital (if admitted) or in the home. There will be no physical contact between study staff and participants. Mothers will express and collect whole breastmilk on Days 0 (enrollment), 3, 10, 19, 28, and 90, breast skin swabs on Days 0 and 3 and whole blood by fingerstick on days 0 and 90. They will also be instructed to provide a frozen HM sample from Day -7, if available. Analysis: RNA will be extracted from HM and breast skin swabs in the Jarvinen-Seppo lab. SARS- CoV-2 genomic RNA will be quantitated using RT-qPCR three amplicon probe-based system as recommended by CDC. We will compare presence and changes in SARS-CoV-2 in HM via repeated measures analysis. We will assess SARS-CoV-2 and other coronavirus antibodies in maternal finger prick and HM to S and N proteins of SARS1, SARS2, HKU1, 229E, NL63 and OC43 by Luminex on the mPLEX-CoV system developed and validated by the Zand lab. Repeated measures analysis will be used to compare the changes in concentration of HM anti-SARS-CoV-2 antibodies over the time-course of disease progression and also between women with mild to severe symptoms. Impact: These results are critical to understand the risks and benefits of breastfeeding in the context of COVID-19 infection, and are necessary to make evidence-based policies, and to care for these families.

背景：人牛奶中SARS-COV-2病毒的传播仅为11 描述的研究很差，报告了36个母乳样本中只有1个可检测到的病毒。更远，怀孕期间的母体SARS-COV-2感染可能会赋予某些特定通过抗体保护。只有一项研究报告了IgG的存在于SARS-COV-2 在HM中。其他病毒感染的抗体依赖性增强的令人震惊的例子说明了如何至关重要的是了解HM中这些抗体的谱和活性。那是至关重要的了解母亲和儿童之间的传播风险和保护因素哺乳。设计：我们提出了一项对1900+母亲的纵向队列研究，以确定传播（通过在HM中和乳晕皮中存在母乳喂养的婴儿通过母乳喂养病毒）和保护因子（HM中和中和的SARS-COV-2特异性抗体反应母乳喂养的能力。纵向样本将使我们能够评估疾病的时间变化课程。方法：我们将在泌乳的前三个月中注册50个covid+母亲，25个有症状和25 无症状。我们将同时从两个地点收集样品：罗切斯特大学医学与牙科学院和纽约大学。这些站点将提供强大的功能，并且交错接触患者。我们将通过当地医院和社交媒体平台招募。母亲将提供知情的信息。 IRB已获得IRB批准。所有样本将在医院（如果被录取）或在家中。研究人员之间没有身体接触和参与者。母亲将在第0天（入学人数），第3、10、19页表达和收集整个母乳。 28和90，第0天和第3天的乳房拭子，以及在第0天和90天通过指尖。还将指示从第-7天开始提供冷冻的HM样品。分析：RNA将从Jarvinen-Seppo实验室中的HM和乳房拭子中提取。 sars- COV-2基因组RNA将使用RT-QPCR三个基于探针的系统进行定量按照CDC的建议。我们将通过重复比较HM中SARS-COV-2的存在和变化措施分析。我们将评估母体手指中的SARS-COV-2和其他冠状病毒抗体 SARS1，SARS2，HKU1、229E，NL63和OC43的刺和HM至S和N蛋白。 MPLEX-COV系统由Zand Lab开发和验证。重复测量分析将是用于比较时间顺序的HM抗SARS-COV-2抗体的浓度变化疾病进展以及轻度至重度症状的女性之间的发展。影响：这些结果对于了解母乳喂养的风险和益处至关重要 Covid-19-19感染是制定基于证据的政策和照顾这些家庭所必需的。