Rowe Julie, Yerkovich Stephanie T, Richmond Peter, Suriyaarachchi Devinda, Fisher Elizabeth, Feddema Leonie, Loh Richard, Sly Peter D, Holt Patrick G
Division of Cell Biology, Telethon Institute for Child Health Research, P.O. Box 855, West Perth WA 6872, Australia.
Infect Immun. 2005 Dec;73(12):8130-5. doi: 10.1128/IAI.73.12.8130-8135.2005.
Acellular vaccines against diphtheria-tetanus-pertussis (acellular pertussis) (DTaP) are being progressively introduced into vaccination programs worldwide, with the aim of reducing T-helper 1 (Th1)-associated reactogenicity associated with the cellular diphtheria-tetanus-pertussis (whole-cell pertussis) (DTwP) vaccine. The DTaP vaccine has an improved safety profile in infants, but little information is available concerning the nature of the ensuing immunological memory in older children and how this may affect the reactogenicity of DTaP booster doses. We have addressed this question in the present study by assessing polyclonal and vaccine antigen-specific humoral and cellular immune responses to boosting with DTaP in 4- to 6-year-old children primed during infancy with DTaP (n = 30) or DTwP (n = 16) and by correlating these parameters, in particular cytokine responses, with expression of local side effects at the injection site. Large local reactions (> or =50-mm diameter) 24 to 72 h after receiving the DTaP booster occurred in 43% of exclusively DTaP-primed children, in contrast to 6% of children primed with DTwP. These reactions were associated with vigorous T helper 2 (Th2)-polarized memory responses to vaccine antigen exemplified by interleukin 5 (IL-5), IL-6, and IL-13 production and log-scale boosting of tetanus-specific immunoglobulin E and occurred most frequently among children who are intrinsically "high Th2 responders" as detected by in vitro responsiveness to polyclonal mitogen. Our findings suggest that priming during infancy with DTaP promotes stable, boostable Th2-polarized immunity against vaccine antigens, which in a significant subset of children is subsequently associated with local reactions at the booster site. The time course of these reactions suggests that the underlying mechanism involves reactivation of Th2-polarized cellular immune memory.
白喉-破伤风-百日咳无细胞疫苗（无细胞百日咳）（DTaP）正在逐步被引入全球疫苗接种计划，目的是降低与细胞型白喉-破伤风-百日咳（全细胞百日咳）（DTwP）疫苗相关的辅助性T细胞1（Th1）相关反应原性。DTaP疫苗在婴儿中的安全性有所改善，但关于大龄儿童后续免疫记忆的性质以及这可能如何影响DTaP加强剂量的反应原性的信息却很少。在本研究中，我们通过评估4至6岁儿童在婴儿期接种DTaP（n = 30）或DTwP（n = 16）后对DTaP加强免疫的多克隆和疫苗抗原特异性体液及细胞免疫反应，并将这些参数，特别是细胞因子反应，与注射部位局部副作用的表现相关联，来解决这个问题。在接受DTaP加强免疫后24至72小时，43%仅接种DTaP的儿童出现了直径大于或等于50毫米的大局部反应，相比之下，接种DTwP的儿童中这一比例为6%。这些反应与对疫苗抗原的强烈辅助性T细胞2（Th2）极化记忆反应相关，以白细胞介素5（IL-5）、IL-6和IL-13的产生以及破伤风特异性免疫球蛋白E的对数级增加为特征，并且在通过对多克隆有丝分裂原的体外反应性检测为本质上“高Th2反应者”的儿童中最为常见。我们的研究结果表明，婴儿期接种DTaP可促进针对疫苗抗原的稳定、可增强的Th2极化免疫，在相当一部分儿童中，这随后与加强免疫部位的局部反应相关。这些反应的时间进程表明，潜在机制涉及Th2极化细胞免疫记忆的重新激活。
