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: 10065972
• 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/10065972
• 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; Genetic Transcription; 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.

孕妇的免疫接种越来越多地用于保护母亲和/或婴儿免受疫苗的伤害。 可预防的疾病。然而，关于母体接种疫苗对婴儿的影响的知识很少。 免疫反应。越来越多的证据表明，婴儿可以在子宫内形成对母体的反应 疫苗。我们假设，在子宫内接触母体流感疫苗(IIV)抗原可能会产生 婴儿在宫内对流感的适应性反应可能会保护婴儿免受疾病的影响 母体抗体在婴儿循环中降低到保护阈值以下。相反，在子宫中 免疫也可能产生调节性T细胞(Treg)，下调婴儿对童年的反应 疫苗。为了解决这些假设，我们制定了以下具体目标： 目的1.检测宫内免疫中的IIV感染率和流感特异性抗体的持久性 宫内免疫后的细胞免疫应答。 通过脐带血中存在流感特异性IgA、T细胞或B细胞来识别接种过IIVV的婴儿 这超过了未接触IIV的婴儿相应标志物的第99个百分位数。坚持不懈将 定义为6至18个月龄时存在流感特异性IgA抗体、记忆B细胞和T细胞， 在给婴儿注射第一剂IIV之前。 目的2.确定宫内免疫中IIV对后续免疫应答的影响 在生命6至18个月时进行儿科静脉注射。 我们将测量流感特异性体液和细胞免疫反应对首次给药的儿科 主要是通过与未接触IIV的婴儿进行比较，发现接受IIV免疫的婴儿中存在IIV。回应 在这方面的测量将包括流感特异性抗体，效应和记忆B细胞和T细胞及其 转录档案。我们将在儿科静脉注射前将流感特异性Treg的比例关联起来 在完成两剂IIV后产生的获得性免疫反应的大小 儿科初级免疫接种时间表。 目的3.比较子宫内免疫产生的流感特异性T细胞的表观遗传学特征 6至18个月的儿科静脉注射。 流感病毒体外刺激乙型脑炎疫苗免疫的CBMC和婴儿De的PBMC后T细胞的增殖 Novo免疫婴儿将被纯化，他们的表观遗传学特征将使用ATAC-Seq进行比较。 这项研究的结果将决定胎儿的质量、耐用性和表观遗传学特征 母体接种引起的对外来抗原的免疫反应。它将定义子宫内的影响 关于新生儿免疫的免疫接种，并告知孕期接种疫苗的做法。