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荷兰4岁儿童连续五次接种无细胞百日咳疫苗前后的T细胞反应。

T-cell responses before and after the fifth consecutive acellular pertussis vaccination in 4-year-old Dutch children.

作者信息

Schure Rose-Minke, Hendrikx Lotte H, de Rond Lia G H, Oztürk Kemal, Sanders Elisabeth A M, Berbers Guy A M, Buisman Anne-Marie

机构信息

Laboratory for Infectious Disease and Perinatal Screening, Center for Infectious Diseases Control, National Institute for Public Health, Bilthoven, The Netherlands.

出版信息

Clin Vaccine Immunol. 2012 Nov;19(11):1879-86. doi: 10.1128/CVI.00277-12. Epub 2012 Sep 26.

Abstract

Immunization with acellular pertussis vaccine (aP) induces higher specific antibody levels and fewer adverse reactions than does immunization with the whole-cell vaccine (wP). However, antibody levels in infants induced by both types of pertussis vaccines wane already after 1 year. Therefore, long-term T-cell responses upon vaccination might play a role in protection against pertussis. In a cross-sectional study (ISRCTN65428640), we investigated T-helper (Th) cell immune responses in wP- or aP-vaccinated children before and after an aP low-dose or high-dose preschool booster at 4 years of age in The Netherlands. T cells were stimulated with pertussis vaccine antigens. The numbers of gamma interferon-producing cells and Th1, Th2, Th17, and interleukin-10 (IL-10) cytokine concentrations were determined. In addition, pertussis-specific IgE levels were measured in plasma. Children being vaccinated with aP vaccinations at 2, 3, 4, and 11 months of age still showed higher pertussis-specific T-cell responses at 4 years of age than did wP-vaccinated children. These T-cell responses failed to show a typical increase in cytokine production after a fifth aP vaccination but remained high after a low-dose booster and seemed to decline even after a high-dose booster. Importantly, elevated IgE levels were induced after this booster vaccination. In contrast, wP-vaccinated children had only low prebooster T-cell responses, and these children showed a clear postbooster T-cell memory response even after a low-dose booster vaccine. Four high-dose aP vaccinations in infancy induce high T-cell responses still present even 3 years after vaccination and enhanced IgE responses after preschool booster vaccination. Therefore, studies of changes in vaccine dosage, timing of pertussis (booster) vaccinations, and the possible association with local side effects are necessary.

摘要

与全细胞疫苗(wP)免疫相比,无细胞百日咳疫苗(aP)免疫诱导产生的特异性抗体水平更高,不良反应更少。然而,两种类型的百日咳疫苗诱导婴儿产生的抗体水平在1年后就已经下降。因此,疫苗接种后的长期T细胞反应可能在预防百日咳中发挥作用。在一项横断面研究(ISRCTN65428640)中,我们在荷兰调查了4岁的接受wP或aP疫苗接种的儿童在4岁时接受低剂量或高剂量aP学龄前加强免疫前后的辅助性T(Th)细胞免疫反应。用百日咳疫苗抗原刺激T细胞。测定产生γ干扰素的细胞数量以及Th1、Th2、Th17和白细胞介素10(IL-10)细胞因子浓度。此外,还测定了血浆中百日咳特异性IgE水平。在2、3、4和11月龄接种aP疫苗的儿童在4岁时仍比接种wP疫苗的儿童表现出更高的百日咳特异性T细胞反应。这些T细胞反应在第五次接种aP疫苗后未能显示出细胞因子产生的典型增加,但在低剂量加强免疫后仍保持较高水平,甚至在高剂量加强免疫后似乎有所下降。重要的是,这次加强免疫后诱导产生了升高的IgE水平。相比之下,接种wP疫苗的儿童在加强免疫前的T细胞反应较低,并且这些儿童即使在低剂量加强疫苗接种后也表现出明显的加强免疫后T细胞记忆反应。婴儿期接种四次高剂量aP疫苗可诱导产生高T细胞反应,即使在接种后3年仍然存在,并且在学龄前加强免疫后增强了IgE反应。因此,有必要研究疫苗剂量变化、百日咳(加强)疫苗接种时间以及与局部副作用的可能关联。

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