Antibody & Cellular Immune responses in children after 2 vs 3 doses and pre vs post booster of PCV13 Vaccine

摘要： 世界卫生组织最近关于肺炎球菌结合疫苗的政策声明 (PCV)批准了一项不加助剂的3次初级接种时间表(3P0时间表)，或作为新的 考虑到低成本，2个初级剂量和一个加强剂量(2P-1时间表)可供选择 收入国家。 PCV13在美国获得了3次主要剂量的许可，外加1次增强剂(3P 1时间表) 经2项美国大型临床试验证明疗效显著。清醒的认识 减少PCV剂量计划对保护性抗体水平和 缺乏免疫B细胞和T细胞记忆的功能和诱导。这项研究将 测定接受2次、3次主要剂量儿童的特异性免疫反应 和3p1剂量的PCV13，并首次提供了直接比较的免疫球蛋白抗体 水平、功能抗体差异和细胞免疫记忆差异 一群孩子。 与临床相关的抗体、功能性抗体和 记忆B细胞和CD4T细胞反应可以在2岁后测量，而不是3岁以下 PCV13剂量和第二年生命中刺激临床相关的强化剂量 抗体、记忆B细胞和CD4T细胞反应增加。我们将对此进行探索 通过比较预期采集的中国人血液样本中的免疫反应来提出假说 婴儿在2p剂量与3p剂量的PCV13和加强前后的PCV13。预期收集的数据 在接种PCV13疫苗后4个时间点的儿童血液样本将被分析以定量 免疫反应的差异。来自美国纽约罗切斯特的6-18个月大的健康儿童 将在PCV13剂量后对血浆和免疫细胞样本进行研究。这项研究将 提供一种新的抗体水平和功能以及B细胞和T细胞记忆的评估 2p剂量与3p剂量以及加强前后对所有PCV13血清型的免疫应答 儿童的剂量。值得注意的是，很少有研究关注针对所有13种病毒的抗体反应。 一组儿童中的多糖组和没有一组儿童同时专注于检测B- 和T细胞特有的记忆。这些发现将加强或质疑影响政策决策 世界各地的儿童关于PCV管理时间表的建议。理解 不同剂量PCV13对补充记忆B细胞池和T辅助细胞的影响 细胞将提供有价值的信息，以评估免疫计划的任何变化。

Abstract: The recent World Health Organization policy statement on pneumococcal conjugate vaccines (PCVs) endorsed a schedule of 3 primary doses without a booster (3p+0 schedule) or, as a new alternative, 2 primary doses with a booster dose (2p+1 schedule) considering the cost for low- income countries. PCV13 was licensed in the U.S. for 3 primary doses plus a booster (3p+1 schedule) supported by high efficacy demonstrated by 2 large scales US-based clinical trials. A clear understanding of the full impact of reduced-dose schedules of PCV on protective antibody levels and functionality as well as induction of immunologic B- and T- cell memory is lacking. This study will determine specific immune responses of children receiving 2 primary doses, 3 primary doses and 3p+1 doses of PCV13 and provide for the first time direct comparison of IgG antibody levels, functional antibody differences and cellular immune memory differences in the same cohort of children. Clinically relevant significant differences in levels of antibodies, functional antibodies, and memory B-cell and CD4+ T-cell responses can be measured after 2 compared to 3 primary doses of PCV13 and a booster dose in the second year of life that stimulates clinically relevant increases in antibodies, memory B-cell and CD4+ T-cell responses. We will explore this hypothesis by comparing immune responses in prospectively collected blood samples from infants after 2p vs. 3p doses of PCV13 and pre vs. post booster PCV13. Prospectively collected blood samples of children at 4 time points after PCV13 doses will be analyzed to quantitate differences in immune responses. Healthy children aged 6-18 months from Rochester, NY, USA will have samples of plasma and immune cells studied after PCV13 doses. The study will provide a novel assessment of antibody levels and functionality as well as B- and T-cell memory immune responses against all PCV13 serotypes following 2p vs. 3p doses and pre vs. post booster doses in children. Remarkably few studies have looked at the antibody responses against all 13 polysaccharides in one cohort of children and none have simultaneously focused on examination of B- and T-cell specific memory. The findings will strengthen or bring to question policy decisions impacting children worldwide regarding recommendations for PCV administration schedules. Understanding the impact of each dose of PCV13 to generate replenished memory B-cell pool and T helper cells will provide valuable information to assess any changes in immunization schedules.