INFLUENZA-SPECIFIC IMMUNITY AND RESPONSES TO INACTIVATED INFLUENZA VACCINE IN INFANTS: EFFECT OF MATERNAL VACCINATION DURING PREGNANCY

婴儿流感特异性免疫力和对灭活流感疫苗的反应：怀孕期间母亲接种疫苗的影响

• 批准号: 10197834
• 负责人: ADRIANA WEINBERG
• 金额: $ 46.65万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-18 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10197834
• 关键词: ATAC-seq; Address; Age-Months; Antibodies; Antibody Response; Antibody titer measurement; Antigens; B-Lymphocytes; Blood Circulation; Cellular Immunity; Characteristics; Childhood; Conjugate Vaccines; Diphtheria; Diphtheria Toxoid; Disease; Dose; Epigenetic Process; Exposure to; Fetus; Gene Expression Profile; Gestational Age; Haemophilus influenzae; Humoral Immunities; Immune response; Immunity; Immunization; Immunization Schedule; Immunize; Immunoglobulin A; Infant; Influenza; Influenza B Virus; Influenza vaccination; Knowledge; Life; Maternal antibody; Measures; Memory B-Lymphocyte; Mothers; Neisseria meningitidis; Peripheral Blood Mononuclear Cell; Pertussis; Pertussis Vaccine; Phenotype; Placenta; Pregnancy; Pregnant Women; Proliferating; Regulatory T-Lymphocyte; Role; T-Lymphocyte; Tetanus; Umbilical Cord Blood; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; adaptive immune response; booster vaccine; fetal; flu; immunogenicity; in utero; influenza virus vaccine; maternal vaccination; neonatal immunity; prenatal exposure; response

Immunization of pregnant women is increasingly used to protect mothers and/or infants against vaccine- preventable diseases. However, there is little knowledge on the effects of maternal vaccination on infant immune responses. There is growing evidence that infants can develop in utero responses to maternal vaccines. We hypothesized that in utero exposure to maternal influenza vaccine (IIV) antigens may generate infant adaptive responses against influenza in utero that may protect the infant against the disease after maternal antibodies decrease in infant circulation below the threshold of protection. Conversely, in utero immunization also may generate regulatory T cells (Treg) that downregulate the infant responses to childhood vaccines. To address these hypotheses, we formulated the following specific aims: Aim 1. To determine the rate of IIV in utero immunization and the persistence of Flu-specific antibody and cellular immune responses after in utero immunization. IIV-exposed immunized infants will be identified by presence of Flu-specific IgA, T cells, or B cells in cord blood that exceed the 99th percentile of the corresponding markers in IIV-unexposed infants. Persistence will be defined by the presence of Flu-specific IgA antibodies, memory B cells and T cells at 6 to 18 months of age, before the administration of the 1st dose of IIV to the infant. Aim 2. To determine the effect of IIV in utero immunization on subsequent immune responses to pediatric IIV administered at 6 to 18 months of life. We will measure Flu-specific humoral and cellular immune responses to the initial administration of pediatric IIV in IIV-exposed immunized infants primarily by comparison with IIV-unexposed infants. Responses measured in this will consist of Flu-specific antibodies, effector and memory B cells and T cells and their transcription profiles. We will correlate the proportions of Flu-specific Treg before pediatric IIV administration with the magnitude of the adaptive immune responses developed after completion of the 2 doses of IIV in the primary pediatric immunization schedule. Aim 3. To compare the epigenetic profile of Flu-specific T cells generated by in utero immunization or pediatric IIV administration at 6 to 18 months of life. T cells that proliferate after ex vivo Flu stimulation of CBMC of IIV-exposed immunized or infant PBMC from de novo immunized infants will be purified and their epigenetic profile will be compared using ATAC-Seq. The results of this study will determine the quality, durability and the epigenetic characteristics of the fetal immune responses to foreign antigens introduced by maternal vaccination. It will define the effect of in utero immunization on neonatal immunity and inform the practice of vaccination during pregnancy.

越来越多地使用孕妇的免疫来保护母亲和/或婴儿免受疫苗的侵害。 可预防的疾病。但是，关于孕产妇疫苗接种对婴儿的影响的知识很少 免疫反应。越来越多的证据表明婴儿可以在子宫对母亲的反应中发展 疫苗。我们假设在子宫内暴露于母体流感疫苗（IIV）抗原可能会产生 婴儿对子宫流感的婴儿自适应反应可能会保护婴儿免受疾病的影响 孕产妇抗体在保护阈值以下的婴儿循环中降低。相反，在子宫里 免疫也可能产生调节性T细胞（TREG），以下调婴儿对儿童时期的反应 疫苗。为了解决这些假设，我们提出了以下具体目的： 目的1。确定子宫免疫中的IIV速率和流感特异性抗体的持久性 子宫免疫后的细胞免疫反应。 通过存在流感特异性IgA，T细胞或B细胞中的IIV暴露的免疫婴儿将被鉴定 超过IIV无暴露婴儿中相应标记的第99个百分位数。持久将是 由6至18个月大的记忆B细胞和T细胞的存在定义 在将IIV的第一剂施用给婴儿之前。 目标2。确定IIV在子宫免疫中对随后对免疫反应的影响 儿科IIV在6至18个月的生命中给药。 我们将测量针对小儿初始给药的流感特异性体液和细胞免疫反应 IIV在IIV暴露的免疫婴儿中主要通过与IIV无暴露的婴儿进行比较。回答 在此中测量的将由流感特异性抗体，效应子和记忆B细胞和T细胞及其 转录曲线。我们将在小儿IIV给药之前将流感特异性Treg的比例关联 随着2剂IIV的完成后，自适应免疫反应的大小 初级小儿免疫计划。 目标3。比较子宫免疫或 小儿IIV管理时期为6至18个月。 在体内流感刺激IIV暴露于IIV的免疫或婴儿PBMC的CBMC刺激后增殖的T细胞 Novo免疫婴儿将被纯化，并使用ATAC-SEQ比较其表观遗传学特征。 这项研究的结果将确定胎儿的质量，耐用性和表观遗传特征 母体疫苗接种引入的对外国抗原的免疫反应。它将定义子宫中的效果 对新生儿免疫的免疫接种并为怀孕期间的疫苗接种实践提供了信息。