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.

孕妇免疫接种越来越多地用于保护母亲和/或婴儿免受疫苗接种- 可预防的疾病。然而，关于母亲接种疫苗对婴儿的影响， 免疫反应。越来越多的证据表明，婴儿可以在子宫内对母亲的反应， 疫苗。我们假设子宫内暴露于母体流感疫苗（IIV）抗原可能会产生 婴儿在子宫内对流感的适应性反应，可以保护婴儿免受疾病的影响， 母体抗体在婴儿循环中下降到保护阈值以下。相反，在子宫内， 免疫接种还可以产生下调婴儿对童年期应答的调节性T细胞（Treg 疫苗。为了解决这些假设，我们制定了以下具体目标： 目标1。测定宫内IIV免疫率和流感特异性抗体持续时间 和子宫内免疫后的细胞免疫应答。 通过脐带血中是否存在流感特异性伊加、T细胞或B细胞来识别IV暴露的免疫婴儿 超过IIV未暴露婴儿相应标志物的第99百分位数。坚持将是 通过在6至18个月龄时存在流感特异性伊加抗体、记忆B细胞和T细胞来定义， 在婴儿接受第一剂IIV给药前。 目标2.为了确定子宫内IIV免疫对随后的免疫应答的影响， 在6至18个月龄时给予儿科IIV。 我们将测量流感特异性体液和细胞免疫反应的初始管理的儿科 主要通过与未暴露于IIV的婴儿进行比较，发现暴露于IIV的免疫婴儿中存在IIV。响应 在此测量的细胞将由流感特异性抗体、效应和记忆B细胞和T细胞及其受体组成。 转录谱我们将在儿科IIV给药前将流感特异性Treg的比例 在完成2次IIV给药后， 儿童初级免疫接种计划。 目标3。为了比较通过子宫内免疫或免疫后产生的流感特异性T细胞的表观遗传特征， 在6至18个月时进行儿科IIV给药。 在体外流感刺激暴露于IV的免疫或婴儿PBMC的CBMC后，T细胞增殖， 将纯化新生免疫的婴儿，并使用ATAC-Seq比较其表观遗传谱。 这项研究的结果将确定胎儿的质量，耐久性和表观遗传特征 对母体接种引入的外来抗原的免疫应答。它将定义在子宫内的影响 预防接种对新生儿免疫力的影响，并告知怀孕期间接种疫苗的做法。