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.
Clin Infect Dis. 2019 Mar 19;68(7):1213-1222. doi: 10.1093/cid/ciy594.
Protection induced by acellular pertussis (aP) vaccines is partial and short-lived, especially in teenagers, calling for novel immunization strategies.
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.
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.
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.
NCT02946190.
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。
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。
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。
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。
NCT02946190。