Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial

Video related to the article "Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial"
(Vaccine. 2021 Mar 12;39(11):1598-1608.)

Abstract
Background: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination.

Methods: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7-366/7 weeks' gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11-18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively.

Results: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4-1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related).

Conclusions: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation.

Clinical trial registration: ClinicalTrials.gov: NCT02853929.

本数据集为与论文《母体无细胞白喉-破伤风-百日咳疫苗接种对幼儿百日咳加强免疫应答的影响：一项随机试验的随访研究》相关的视频资料，该论文发表于《疫苗》（Vaccine）2021年3月12日;39(11):1598-1608。

摘要
背景：母体接种百日咳疫苗诱导的经胎盘转移抗体，会干扰婴儿对百日咳基础免疫的应答。本研究旨在评估该干扰在幼儿接受加强免疫后是否依然存在。

方法：在一项既往的Ⅳ期、观察者盲法、安慰剂对照随机研究（临床试验编号NCT02377349）中，澳大利亚、加拿大及欧洲的妊娠女性在妊娠27又0/7~36又6/7周时，分别接受肌内注射的破伤风减毒抗原含量白喉三组分无细胞百日咳疫苗（tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine, Tdap）组或安慰剂（对照组），产后可进行交叉免疫接种。其子女先后完成百日咳基础免疫（对应研究编号NCT02422264）及加强免疫（接种于11~18月龄；本研究编号NCT02853929），接种疫苗为无细胞白喉-破伤风-三组分百日咳-乙型肝炎病毒-灭活脊髓灰质炎/乙型流感嗜血杆菌联合疫苗（diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine, DTaP-HepB-IPV/Hib）及13价肺炎球菌结合疫苗。本研究对加强免疫前后的免疫原性、加强免疫的反应原性与安全性进行描述性评估。

结果：共有263名Tdap组幼儿及277名对照组幼儿接受了DTaP-HepB-IPV/Hib加强免疫。加强免疫前，对照组幼儿的3种百日咳抗原及白喉的几何平均浓度（geometric mean concentrations, GMCs）较Tdap组高1.4~1.5倍；其余DTaP-HepB-IPV/Hib所含抗原的GMCs无组间差异。加强免疫后1个月，两组幼儿的百日咳抗原加强免疫应答率均≥92.1%，其余DTaP-HepB-IPV/Hib所含抗原的血清保护率均≥99.2%，达成本研究主要目标。与Tdap组相比，对照组幼儿的抗丝状血凝素（filamentous hemagglutinin）抗体（1.2倍）、抗百日咳类毒素（pertussis toxoid）抗体（1.5倍）及抗白喉抗体（1.4倍）的加强免疫后GMCs更高；其余DTaP-HepB-IPV/Hib所含抗原的GMCs组间无显著差异。共有3名幼儿报告了严重不良事件（均来自对照组，与疫苗接种无关）。加强免疫前发生1例死亡（来自Tdap组，与疫苗接种无关）。

结论：由于母体百日咳抗体干扰婴儿对百日咳基础免疫的应答，在接受DTaP-HepB-IPV/Hib加强免疫前，母体接种Tdap的幼儿体内的百日咳抗体浓度仍低于对照组幼儿。加强免疫后，幼儿体内针对丝状血凝素与百日咳类毒素的抗体浓度更低，但针对百日咳黏附素的抗体浓度无此差异。该干扰的临床意义尚需进一步评估。

临床试验注册：ClinicalTrials.gov: NCT02853929。