Longitudinal SARS-CoV-2 mRNA vaccine-induced mucosal, serological, and cellular immunity in children and human milk

纵向 SARS-CoV-2 mRNA 疫苗诱导儿童和母乳中的粘膜、血清学和细胞免疫

基本信息

批准号：
10568736
负责人：
Pia S Pannaraj
金额：
$ 80.06万
依托单位：
CHILDREN'S HOSPITAL OF LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-21 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10568736
关键词：
2019-nCoV Address Adolescent Adult Age Age-Months Antibodies Antibody Response Bar Codes Bioinformatics Biological Biological Assay Blood specimen Breast Feeding Breastfed infant CD8-Positive T-Lymphocytes CD8B1 gene COVID-19 COVID-19 vaccination COVID-19 vaccine Cells Cellular Immunity Child Clinical Trials DNA Data Dose Enrollment Ensure Enzyme-Linked Immunosorbent Assay Epidemiology Epitopes FDA Emergency Use Authorization Genetic Transcription Hospitalization Household Human Milk Humoral Immunities Immune response Immune system Immunity Immunoglobulin A Immunoglobulin G Immunologics Immunology Individual Infant Infection Lactation Life Longevity Maternal Messenger RNA Measures Methods Milk Mothers Mucosal Immunity Mucous Membrane Nose Participant Pathway interactions Peripheral Blood Mononuclear Cell Pfizer-BioNTech COVID-19 vaccine Policy Maker Population Proteins RNA RNA vaccination RNA vaccine Recording of previous events Respiratory System Reverse Transcriptase Polymerase Chain Reaction SARS-CoV-2 antibody SARS-CoV-2 exposure SARS-CoV-2 immunity SARS-CoV-2 infection Saliva Sampling Scientist Secretory Immunoglobulin A Serology Serum Site Source Specimen Stains Structure of mucous membrane of nose System T cell receptor repertoire sequencing T cell response T-Cell Activation T-Lymphocyte Testing Time Tissue-Specific Gene Expression United States Up-Regulation Upper respiratory tract Vaccination Vaccines Viral Whole Blood age group breakthrough infection child protection cohort community transmission cytokine experience high risk maternal vaccination neutralizing antibody predicting response pregnant prevent response sample collection symptomatic COVID-19 transcriptomics transmission process vaccination strategy vaccine evaluation vaccinology virology

项目摘要

PROJECT SUMMARY COVID-19 cases and hospitalizations in children have increased dramatically worldwide. Although most COVID- 19 is mild in children, severe illness and post-infectious complications can occur. We and others have found that children are an important source of household and community transmission. Vaccination is the most effective way to prevent severe infection and decrease transmission. Infants under 6 months of age are at high risk for life-threatening complications, but a vaccine for this age group is not yet in clinical trials; thus, maternal vaccination and breastfeeding may be an important strategy to protect infects. SARS-CoV-2 infection and vaccine immunity studies have focused predominantly on adults, but children have developing immune systems and may respond to the new mRNA vaccination platform differently from adults. This proposal addresses the critical need to study the short- and long-term immune responses to COVID-19 mRNA vaccination in children, human milk, and breastfeeding infants. We have a successful ongoing longitudinal COVID-19 vaccination cohort that began in December 2020, in which we have collected biologic specimens from 368 individuals including adults, children, and lactating mother-infant pairs. We will enroll a total of 560 individuals down to 6 months of age after the mRNA vaccine receives Emergency Use Authorization (EUA) for the younger age group. Participants are followed every 3 months for nasal, saliva, milk (if lactating), and blood samples. We will test all COVID-19 symptomatic or exposed participants for breakthrough infection throughout the study period. Our central hypothesis is that the repertoire, magnitude, and longevity of COVID-19 vaccine- induced immune responses will be dependent on age and previous experience with SARS-CoV-2 infection. Importantly, our study will also move beyond the systemic immune responses to examine mucosal immunity in the respiratory tract and in human milk. To test the hypothesis, we will characterize vaccine induced serum, nasal, and saliva SARS-CoV-2-specific antibody response (Aim 1) and cellular (CD4+/CD8+) response (Aim 2) in children compared with adults and identify key immunologic correlates of protection against breakthrough infection. We will also determine humoral and cellular responses in human milk and secretory IgA in the breastfed infants’ upper respiratory tract and evaluate vaccine-induced differential gene expression in milk that direct the immune response (Aim 3). Our collaborative team with expertise in vaccinology, immunology, virology, epidemiology, and bioinformatics will ensure successful integrative analyses and interpretation of these immunologic and transcriptomic data. Completion of the study will provide a comprehensive characterization of longitudinal COVID-19 mRNA vaccination-induced immunity across age groups and in human milk to inform vaccination strategies to optimize the protection of children and infants.

项目概要全球范围内的 COVID-19 病例和住院人数急剧增加。 19在儿童中是轻微的，可能会出现严重的疾病和感染后并发症。儿童是家庭和社区传播的重要来源，疫苗接种是最有效的。预防严重感染并减少传播的方法。 6 个月以下的婴儿面临高风险。危及生命的并发症，但针对该年龄组的疫苗尚未进入临床试验，因此，母亲；疫苗接种和母乳喂养可能是预防感染 SARS-CoV-2 的重要策略。疫苗免疫研究主要集中于成人，但儿童的免疫能力正在发育系统对新的 mRNA 疫苗接种平台的反应可能与成人不同。解决了研究 COVID-19 mRNA 疫苗接种的短期和长期免疫反应的迫切需要我们在儿童、母乳和母乳喂养的婴儿中成功开展了一项持续的纵向COVID-19研究。 2020 年 12 月开始的疫苗接种队列，我们收集了 368 名患者的生物样本个人，包括成人、儿童和哺乳期母婴，我们总共将招募 560 名个人。 mRNA 疫苗获得儿童紧急使用授权 (EUA) 后，年龄可降至 6 个月大每 3 个月对参与者进行一次鼻腔、唾液、乳汁（如果是哺乳期）和血液样本的随访。将在整个研究过程中测试所有有 COVID-19 症状或接触过的参与者是否出现突破性感染我们的中心假设是，COVID-19 疫苗的种类、规模和寿命- 诱导的免疫反应将取决于年龄和之前接触 SARS-CoV-2 的经验重要的是，我们的研究还将超越全身免疫反应来检查。为了检验这一假设，我们将描述呼吸道和人乳中的粘膜免疫。疫苗诱导血清、鼻腔和唾液 SARS-CoV-2 特异性抗体反应（目标 1）和细胞与成人相比，儿童的 (CD4+/CD8+) 反应（目标 2）并确定关键的免疫相关性我们还将确定母乳中的体液和细胞反应。母乳喂养婴儿上呼吸道分泌型IgA和分泌型IgA的检测及疫苗诱导差异基因评价牛奶中的表达可指导免疫反应（目标 3）。免疫学、病毒学、流行病学和生物信息学将确保成功的综合分析和对这些免疫学和转录组数据的解释将提供研究的完成。纵向 COVID-19 mRNA 疫苗接种诱导的跨年龄免疫力的综合表征群体和母乳中的信息，以告知疫苗接种策略，以优化对儿童和婴儿的保护。