Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Department of Paediatrics, Spaarne Hospital, Hoofddorp, the Netherlands.
Vaccine. 2020 Jun 15;38(29):4632-4639. doi: 10.1016/j.vaccine.2020.04.001. Epub 2020 May 21.
Maternal antibody levels after Tdap vaccination during pregnancy may affect infant primary antibody responses to pertussis, Tetanus toxoid (TT), Diphtheria toxoid (DT) vaccinations and pneumococcal vaccines with diphtheria toxin mutants like CRM197 as carrier protein.
Mothers were recruited in an open label randomised parallel controlled trial in 2014-2016 through midwifes. They received Tdap [Boostrix] at 30-32 weeks of pregnancy (n = 58) or within 48 h after delivery (n = 60). Infants received DTaP-IPV-Hib-HepB [Infanrix Hexa] and 10-valent protein D conjugated pneumococcal conjugate vaccine (PHiD-CV10 [Synflorix]) at age 3, 5 and 11 months. We now report on infant specific IgG levels towards DT, TT, Haemophilus influenzae type b polyribosylribitol phosphate (Hib PRP) and PHiD-CV10 before and after primary- and booster vaccination as secondary study endpoints; pertussis antibodies were the primary endpoint of the study. This trial is registered in clinicaltrialsregister.eu (EudraCT 2012-004006-9) and trialregister.nl (NTR number NTR4314).
Post primary vaccinations, antibody levels to DT, but not TT, were significantly lower after Tdap vaccination during pregnancy compared to controls (GMC ratio 0.4, 95% CI 0.3-0.6 and 0.9, 95% CI 0.6-1.2, respectively). Antibodies to serotype 19F were significantly lower in the maternal Tdap group, whereas there were no differences in antibody levels to Hib PRP and the other 9 pneumococcal serotypes. Post booster vaccinations, no significant differences were observed, except for DT.
Maternal Tdap vaccination results in significant interference with infants responses not only to DT but also to conjugated pneumococcal vaccines containing DT mutants as carrier proteins. These interactions after maternal Tdap vaccination need to be taken into account when designing infants' national immunization schedules and choice of vaccines.
The Dutch Ministry of Health, Welfare and Sport.
母体在妊娠期间接种 Tdap 疫苗后的抗体水平可能会影响婴儿对百日咳、破伤风类毒素（TT）、白喉类毒素（DT）疫苗和含有白喉类毒素突变体（如 CRM197）作为载体蛋白的肺炎球菌疫苗的原发性抗体反应。
在 2014 年至 2016 年期间，通过助产士以开放标签随机对照平行试验招募母亲。她们在妊娠 30-32 周（n=58）或分娩后 48 小时内（n=60）接受 Tdap [Boostrix]。婴儿在 3、5 和 11 个月时接受 DTaP-IPV-Hib-HepB [Infanrix Hexa]和 10 价蛋白 D 结合肺炎球菌结合疫苗（PHiD-CV10 [Synflorix]）。现在我们报告婴儿在初级和加强免疫前后针对 DT、TT、流感嗜血杆菌 b 型多聚核糖醇磷酸（Hib PRP）和 PHiD-CV10 的特定 IgG 水平，作为次要研究终点；百日咳抗体是该研究的主要终点。该试验在 clinicaltrialsregister.eu（EudraCT 2012-004006-9）和 trialregister.nl（NTR 编号 NTR4314）注册。
在初级免疫后，与对照组相比，妊娠期间接种 Tdap 疫苗后针对 DT 的抗体水平明显较低（GMC 比值分别为 0.4、95%CI 0.3-0.6 和 0.9、95%CI 0.6-1.2）。母体 Tdap 组针对血清型 19F 的抗体水平明显较低，而针对 Hib PRP 和其他 9 种肺炎球菌血清型的抗体水平没有差异。在加强免疫后，除 DT 外，未观察到明显差异。
母体 Tdap 疫苗接种不仅会对 DT 而且会对含有 DT 突变体作为载体蛋白的结合肺炎球菌疫苗产生婴儿应答的显著干扰。在设计婴儿国家免疫计划和疫苗选择时，需要考虑母体 Tdap 疫苗接种后的这些相互作用。
荷兰卫生部、福利和体育部。
