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3次初次给药方案，无加强（3 p +0方案），或作为新的 另一种选择是，考虑到低成本，2次初始剂量加一次加强剂量（2 p +1方案） 收入国家。 PCV 13在美国获得许可，可用于3个主要剂量加一个加强剂量（3 p +1方案） 通过2项大规模美国临床试验证明的高疗效。清醒的认识 减少PCV剂量方案对保护性抗体水平的全面影响， 功能以及免疫B-和T-细胞记忆的诱导是缺乏的。本研究将 确定接受2次主要剂量、3次主要剂量的儿童的特异性免疫应答 和3 p +1剂量的PCV 13，并首次提供IgG抗体的直接比较 水平、功能性抗体差异和细胞免疫记忆差异相同 一群孩子。 抗体、功能性抗体和抗体水平的临床相关显著差异 记忆B细胞和CD 4 + T细胞反应可以在2次后测量，与3次原发性相比， 剂量的PCV 13和第二年的加强剂量，刺激临床相关的 抗体、记忆B细胞和CD 4 + T细胞反应增加。我们将探讨这一点 通过比较前瞻性收集的血液样本中的免疫反应， 婴儿在2 p与3 p剂量的PCV 13后以及加强PCV 13前与后。前瞻性采集 将分析PCV 13给药后4个时间点的儿童血样，以定量 免疫反应的差异。来自美国纽约州罗切斯特的6-18个月的健康儿童 将在PCV 13给药后研究血浆和免疫细胞样本。这项研究将 提供了抗体水平和功能性以及B-和T-细胞记忆的新评估 2 p与3 p剂量后以及加强前与加强后对所有PCV 13血清型的免疫应答 儿童剂量。很少有研究关注针对所有13种抗体的反应 多糖在一个队列的儿童，没有同时集中在检查B- 和T细胞特异性记忆调查结果将加强或质疑政策决定， 关于PCV给药时间表的建议。理解 各剂量PCV 13对产生补充记忆B细胞库和T辅助细胞的影响 细胞将提供有价值的信息，以评估免疫接种计划的任何变化。

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.