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

• 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
• 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

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.

项目摘要 COVID-19案件和儿童的住院病例在全球范围内急剧增加。虽然大多数covid- 19可能发生儿童，严重疾病和感染后并发症。我们和其他人发现 儿童是家庭和社区传播的重要来源。疫苗接种是最有效的 防止严重感染和减少传播的方法。 6个月以下的婴儿有高风险 威胁生命的并发症，但是该年龄组的疫苗尚未在临床试验中；因此，母亲 疫苗接种和母乳喂养可能是保护感染的重要策略。 SARS-COV-2感染和 疫苗免疫学研究主要集中在成年人上，但儿童患有免疫力 系统并可能对新的mRNA疫苗接种平台的反应与成人不同。这个建议 解决研究COVID-19 mRNA疫苗接种的短期和长期免疫反应的关键需求 在儿童中，人牛奶和母乳喂养婴儿。我们有一个持续的纵向Covid-19 从2020年12月开始的疫苗接种队列，我们​​从368中收集了生物标本 包括成年人，儿童和哺乳为母亲的个人。我们将总共注册560个人 mRNA疫苗在年轻人获得紧急使用授权（EUA）之后的6个月大。 年龄段。每3个月，鼻，唾液，牛奶（如果哺乳）和血液样本进行一次参与者。我们 将在整个研究过程中测试所有COVID-19症状或暴露的参与者是否有突破性感染 时期。我们的中心假设是Covid-19疫苗的曲目，幅度和寿命 诱导的免疫反应将取决于年龄和先前的SARS-COV-2经验 感染。重要的是，我们的研究还将超越系统性免疫反应以检查 呼吸道和人乳中的粘膜免疫。为了检验假设，我们将表征 疫苗诱导的血清，鼻和唾液SARS-COV-2特异性抗体反应（AIM 1）和细胞 （CD4+/CD8+）与成人相比的儿童反应（AIM 2），并确定关键的免疫学相关性 防止突破感染。我们还将确定人乳中的体液和细胞反应 母乳喂养婴儿的上呼吸道中的秘密IgA并评估疫苗诱导的差异基因 指导免疫响应的牛奶中的表达（AIM 3）。我们具有疫苗学专业知识的合作团队， 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 这些免疫学和转录组数据的解释。研究的完成将提供 纵向共同199 mRNA疫苗接种诱导的免疫力的全面表征 小组和人牛奶，以告知疫苗接种策略，以优化对儿童和婴儿的保护。