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

孕妇免疫接种越来越多地用于保护母亲和/或婴儿免受疫苗侵害。 可预防的疾病。然而，对于母亲接种疫苗对婴儿的影响知之甚少。 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产生反应 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 婴儿在子宫内对流感的适应性反应可能会保护婴儿在出生后免受这种疾病的侵害 婴儿循环中的母源抗体降低至保护阈值以下。相反，在子宫内 免疫还可能产生调节性 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. 确定子宫内免疫 IIV 率和流感特异性抗体的持续性 和子宫内免疫后的细胞免疫反应。 暴露于 IIV 的免疫婴儿将通过脐带血中是否存在流感特异性 IgA、T 细胞或 B 细胞来识别 超过未暴露于 IIV 的婴儿中相应标记的第 99 个百分位。坚持下去就会 定义为 6 至 18 个月大时存在流感特异性 IgA 抗体、记忆 B 细胞和 T 细胞， 在给婴儿注射第一剂 IIV 之前。 目标 2. 确定子宫内免疫 IIV 对后续免疫反应的影响 儿科 IIV 在出生后 6 至 18 个月时注射。 我们将测量对儿科初次给药的流感特异性体液和细胞免疫反应 主要通过与未暴露 IIV 的婴儿进行比较来比较 IIV 暴露的免疫婴儿的 IIV。回应 其中测量的将包括流感特异性抗体、效应细胞和记忆 B 细胞和 T 细胞及其 转录概况。我们将在儿科 IIV 给药前关联流感特异性 Treg 的比例 完成 2 剂 IIV 后产生的适应性免疫反应的强度 儿童初级免疫接种计划。 目标 3. 比较通过宫内免疫或免疫产生的流感特异性 T 细胞的表观遗传特征 儿科 IIV 在 6 至 18 个月大时给药。 T 细胞在离体流感刺激 IIV 暴露免疫或来自 de 的婴儿 PBMC 的 CBMC 后增殖 novo 免疫婴儿将被纯化，并使用 ATAC-Seq 比较他们的表观遗传图谱。 这项研究的结果将决定胎儿的质量、耐久性和表观遗传特征 对母体疫苗接种引入的外来抗原的免疫反应。它将定义子宫内的影响 免疫接种对新生儿免疫力的影响，并告知怀孕期间的疫苗接种做法。

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.