Variability in Vaccine Response and Trajectory in Early Childhood and Association with Demographic Variables, Antibiotic Exposure and Infection Proneness

Michael E Pichichero, Eduardo Gonzalez, Andrew Cox, Terri C Thayer, Peter Bajorski
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Abstract

Introduction We sought to explore the variability of antibody responses to multiple vaccines during early life in individual children, assess the trajectory of each child longitudinally, determine the associations of demographic variables and antibiotic exposures with vaccine-induced immunity, and link vaccine responsiveness to infection proneness. Methods In 357 prospectively-recruited children, age six through 36 months, antibody levels to 13 routine vaccine antigens were measured in sera at multiple time points and normalized to their respective protective thresholds to categorize children into four groups: very low, low, normal, and high vaccine responder. Demographic variables and frequency of antibiotic exposure data were collected. Participants were followed to determine change in vaccine groups over time and occurrences of infections. Results Vaccine-induced antibody levels persisted over time as very low, low, normal, or high in individual children and changed post-primary through post-booster immunizations against multiple antigen types, including toxoids, purified proteins, polysaccharide-protein conjugates, recombinant proteins and inactivated viruses. Factors influencing persistence or change in vaccine response group were assessed. Children who did not attend day care and African American/multiracial children had higher vaccine-induced antibody levels than White children. Children with lower vaccine-induced antibody levels had more frequent antibiotic exposures. Low vaccine responsiveness was linked to more frequent antibiotic-treated bacterial infections. Conclusion When vaccine-induced antibody levels are used to define vaccine response groups, individual children may persist or change groups over time, which is associated with demographic variables and influenced by antibiotic exposures. Lower vaccine responsiveness can be linked to more frequent antibiotic-treated bacterial infections.
儿童早期疫苗反应和轨迹的可变性及其与人口统计学变量、抗生素暴露和感染易感性的关系
我们试图探索个体儿童生命早期对多种疫苗的抗体反应的可变性,纵向评估每个儿童的轨迹,确定人口统计学变量和抗生素暴露与疫苗诱导免疫的关联,并将疫苗反应与感染易感性联系起来。方法前瞻性招募357名6 ~ 36个月的儿童,在多个时间点检测血清中13种常规疫苗抗原的抗体水平,并将其归一到各自的保护阈值,将儿童分为四组:非常低、低、正常和高疫苗应答。收集人口统计学变量和抗生素暴露频率数据。随访参与者以确定疫苗组随时间的变化和感染发生率。结果疫苗诱导的抗体水平在儿童个体中持续维持在非常低、低、正常或高水平,并在针对多种抗原类型(包括类毒素、纯化蛋白、多糖蛋白偶联物、重组蛋白和灭活病毒)的初次免疫后通过加强免疫后发生变化。评估影响疫苗反应组持续或改变的因素。未参加日托的儿童和非裔美国人/多种族儿童的疫苗诱导抗体水平高于白人儿童。疫苗诱导抗体水平较低的儿童更频繁地接触抗生素。低疫苗反应性与更频繁的抗生素治疗细菌感染有关。当使用疫苗诱导的抗体水平来定义疫苗反应组时,个体儿童可能随着时间的推移而持续存在或改变组,这与人口统计学变量有关,并受抗生素暴露的影响。较低的疫苗反应性可能与更频繁的抗生素治疗细菌感染有关。
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