Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, Netherlands.
Front Immunol. 2018 Jan 24;9:51. doi: 10.3389/fimmu.2018.00051. eCollection 2018.
Pertussis is re-emerging worldwide, despite effective immunization programs for infants and children. Epidemiological studies show a more limited duration of protection against clinical pertussis in adolescents primed with acellular pertussis (aP) vaccines during infancy than those who have been primed with whole-cell pertussis (wP) vaccines. This study aimed to determine whether memory immune responses to aP, diphtheria, and tetanus vaccine antigens following booster vaccinations at 4 and 9 years of age differ between wP- versus aP-primed children.
In a cross-sectional study, blood was collected of DTwP- or diphtheria, tetanus, and aP (DTaP)-primed children before, 1 month, and 2 years after the preschool DTaP booster administered at 4 years of age ( = 41-63 per time point). In a longitudinal study, blood was sampled of DTwP- or DTaP-primed children before, 1 month, and 1 year after a preadolescent Tdap booster at 9 years of age ( = 79-83 per time point). Pertussis, diphtheria, and tetanus vaccine antigen-specific IgG levels, B-cell and T-cell responses were determined.
After the preschool booster vaccination, IgG levels were significantly higher in aP-primed as compared with wP-primed children until 6 years of age. Before the preadolescent Tdap booster vaccination, humoral and cellular immune responses were similar in aP- and wP-primed children. However, the Tdap booster vaccination induced lower vaccine antigen-specific humoral, B-cell, and T-helper 1 (Th1) cell responses resulting in significantly lower Th1/Th2 ratios in aP-primed compared with wP-primed children.
The memory immune profiles at preadolescent age to all DTaP vaccine antigens are already determined by the wP or aP combination vaccines given in infancy, showing a beneficial Th1-dominated response after wP-priming. These immunological data corroborate epidemiological data showing that DTaP-primed adolescents are less protected against clinical pertussis than DTwP-primed children.
尽管婴儿和儿童的百日咳免疫计划有效,但该疾病在全球范围内仍重新出现。流行病学研究表明,与使用全细胞百日咳(wP)疫苗进行基础免疫的青少年相比,使用无细胞百日咳(aP)疫苗进行基础免疫的青少年对临床百日咳的保护作用持续时间更有限。本研究旨在确定在 4 岁和 9 岁时接种加强针后,aP、白喉和破伤风疫苗抗原的记忆免疫反应是否在 wP 疫苗与 aP 疫苗接种的儿童之间存在差异。
在一项横断面研究中,在 4 岁时接种学前 DTaP 加强针(每个时间点有 41-63 名儿童)之前、1 个月和 2 年后,采集 DTwP 或 DTaP 疫苗接种的儿童的血液样本。在一项纵向研究中,在 9 岁时接种青少年 Tdap 加强针(每个时间点有 79-83 名儿童)之前、1 个月和 1 年后采集 DTwP 或 DTaP 疫苗接种的儿童的血液样本。测定百日咳、白喉和破伤风疫苗抗原特异性 IgG 水平、B 细胞和 T 细胞反应。
在学前加强针接种后,aP 疫苗接种组的 IgG 水平在 6 岁之前均显著高于 wP 疫苗接种组。在接种青少年 Tdap 加强针之前,aP 疫苗和 wP 疫苗接种组的体液和细胞免疫反应相似。然而,Tdap 加强针接种诱导的疫苗抗原特异性体液、B 细胞和 T 辅助细胞 1(Th1)细胞反应较低,导致 aP 疫苗接种组的 Th1/Th2 比值明显低于 wP 疫苗接种组。
在青少年前,所有 DTaP 疫苗抗原的记忆免疫谱已经由婴儿期使用的 wP 或 aP 联合疫苗决定,wP 疫苗接种后产生有益的 Th1 优势反应。这些免疫学数据与流行病学数据一致,表明 DTaP 疫苗接种的青少年对临床百日咳的保护作用不如 DTwP 疫苗接种的儿童。