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含重组或化学灭活百日咳毒素的无细胞百日咳疫苗增强青少年免疫效果:一项随机临床试验。

Boosting Teenagers With Acellular Pertussis Vaccines Containing Recombinant or Chemically Inactivated Pertussis Toxin: A Randomized Clinical Trial.

机构信息

Department of Paediatrics, Children's Hospital of Geneva, University Hospitals of Geneva.

Center for Vaccinology and Neonatal Immunology, Department of Pediatrics and Pathology-Immunology, Medical Faculty and University Hospitals of Geneva, Switzerland.

出版信息

Clin Infect Dis. 2019 Mar 19;68(7):1213-1222. doi: 10.1093/cid/ciy594.

DOI:10.1093/cid/ciy594
PMID:30759183
Abstract

BACKGROUND

Protection induced by acellular pertussis (aP) vaccines is partial and short-lived, especially in teenagers, calling for novel immunization strategies.

METHODS

We conducted an investigator-driven proof-of-concept randomized controlled trial in aP-primed adolescents in Geneva to assess the immunogenicity and reactogenicity of a novel recombinant aP (r-aP) vaccine including recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) coadministered with tetanus-diphtheria toxoids (Td), compared to a licensed tetanus-diphtheria-aP vaccine containing chemically detoxified PT (cd/Tdap). The primary immunological endpoints were day 28/365 geometric mean concentrations (GMCs) of total and neutralizing anti-PT antibodies. Memory B cells were assessed.

RESULTS

Sixty-two aP-primed adolescents were randomized and vaccinated with r-aP + Td or cd/Tdap. Reactogenicity, adverse events, and baseline GMCs were similar between the groups. Day 28 PT-neutralizing GMCs were low after cd/Tdap (73.91 [95% confidence interval {CI}, 49.88-109.52] IU/mL) and approximately 2-fold higher after r-aP + Td (127.68 [95% CI, 96.73-168.53] IU/mL; P = .0162). Anti-PT GMCs were also low after cd/Tdap (52.43 [95% CI, 36.41-75.50] IU/mL) and 2-fold higher after r-aP + Td (113.74 [95% CI, 88.31-146.50] IU/mL; P = .0006). Day 28 anti-FHA GMCs were similar in both groups. Day 365 anti-PT (but not PT-neutralizing) GMCs remained higher in r-aP + Td vaccinees. PT-specific memory B cells increased significantly after r-aP + Td but not cd/Tdap boosting.

CONCLUSIONS

Boosting aP-primed adolescents with r-aP induced higher anti-PT and PT-neutralizing responses than cd/Tdap and increased PT-specific memory B cells. Despite this superior immunogenicity, r-aP may have to be given repeatedly, earlier, and/or with novel adjuvants to exert an optimal influence in aP-primed subjects.

CLINICAL TRIALS REGISTRATION

NCT02946190.

摘要

背景

无细胞百日咳(aP)疫苗诱导的保护作用是部分和短暂的,尤其是在青少年中,这就需要新的免疫策略。

方法

我们在日内瓦对 aP 初免的青少年进行了一项由研究者驱动的概念验证随机对照试验,以评估新型重组 aP(r-aP)疫苗的免疫原性和反应原性,该疫苗包括重组百日咳毒素(PT)和丝状血凝素(FHA)与破伤风类毒素-白喉类毒素(Td)联合使用,与含有化学解毒 PT(cd/Tdap)的许可破伤风类毒素-白喉类毒素-无细胞百日咳疫苗进行比较。主要免疫学终点是第 28/365 天总中和抗-PT 抗体的几何平均浓度(GMC)。评估了记忆 B 细胞。

结果

62 名 aP 初免的青少年被随机分配并接种 r-aP+Td 或 cd/Tdap。两组的反应原性、不良事件和基线 GMC 相似。接种 cd/Tdap 后第 28 天 PT 中和 GMC 较低(73.91 [95%置信区间{CI},49.88-109.52] IU/ml),接种 r-aP+Td 后约高 2 倍(127.68 [95% CI,96.73-168.53] IU/ml;P =.0162)。接种 cd/Tdap 后第 28 天抗-PT GMC 也较低(52.43 [95% CI,36.41-75.50] IU/ml),接种 r-aP+Td 后高 2 倍(113.74 [95% CI,88.31-146.50] IU/ml;P =.0006)。两组第 28 天抗-FHA GMC 相似。r-aP+Td 疫苗接种者第 365 天抗-PT(但非 PT 中和)GMC 仍较高。r-aP+Td 加强后 PT 特异性记忆 B 细胞显著增加,但 cd/Tdap 加强后无明显增加。

结论

在 aP 初免的青少年中加强 r-aP 可诱导更高的抗-PT 和 PT 中和反应,高于 cd/Tdap,并增加了 PT 特异性记忆 B 细胞。尽管具有这种优越的免疫原性,但 r-aP 可能需要重复、更早和/或使用新型佐剂,以在 aP 初免的受试者中发挥最佳作用。

临床试验注册

NCT02946190。

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