University of Western Australia School of Medicine, Department of Immunology, Perth Children's Hospital and Telethon Kids Institute, Nedlands, WA, Australia.
Vaccine and Immunisation Research Group (VIRGo), Peter Doherty Institute for Infection and Immunity at the University of Melbourne and Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Vaccine. 2024 Oct 24;42(24):126251. doi: 10.1016/j.vaccine.2024.126251. Epub 2024 Sep 2.
This phase 1 trial assessed the safety and immunogenicity of an investigational tetanus/diphtheria/acellular pertussis vaccine combined with CpG 1018 adjuvant 1500 μg (Tdap-1018 1500 μg) or 3000 μg (Tdap-1018 3000 μg) in adults and adolescents. In this randomized, active-controlled, multicenter, dose-escalation trial, healthy participants aged 10 to 22 years received 1 dose of Tdap-1018 1500 μg, Tdap-1018 3000 μg, or Boostrix. Geometric mean concentrations (GMCs) and booster response rates (BRRs) for antibodies against pertussis (pertussis toxin, filamentous hemagglutinin, pertactin), tetanus, and diphtheria antigens, and neutralizing antibodies against pertussis toxin were assessed 4 weeks after vaccination. Safety and tolerability were assessed for solicited post-injection reactions within 7 days after vaccination and unsolicited adverse events up to 12 weeks after vaccination. Of 117 enrolled participants, 80 adults (92%) and 30 adolescents (100%) completed the study. Both Tdap-1018 formulations were generally well tolerated, with no vaccine-related serious adverse events. Frequency and severity in post-injection reactions after Tdap-1018 administration were similar to Boostrix except for higher proportions of moderate pain for Tdap-1018. In adults at week 4, ratio of GMCs and BRRs for all antigens in the 3000-μg group were similar to or higher than Boostrix, with significantly higher GMC ratios for anti-pertussis toxin (2.1 [1.5-3.0]) and anti-tetanus (1.8 [1.1-2.9]) and significantly higher BRRs for anti-pertussis toxin (difference [95% CI]: 34.5% [13.4-54.6]), anti-pertactin (19.2% [4.4-38.1]), and anti-tetanus (30.0% [3.6-52.7]) antibodies. For adolescents, in the 3000-μg group, ratio of GMCs and BRRs were similar to or higher than Boostrix for all antigens. Both Tdap-1018 formulations showed acceptable safety and tolerability profiles. Tdap-1018 3000 μg induced similar or higher immune responses than Boostrix. ACTRN12620001177943 (Australian New Zealand Clinical Trials Registry; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12620001177943p).
这项 1 期临床试验评估了一种新型破伤风类毒素/白喉/无细胞百日咳联合 CpG 1018 佐剂 1500μg（Tdap-1018 1500μg）或 3000μg（Tdap-1018 3000μg）在成人和青少年中的安全性和免疫原性。在这项随机、主动对照、多中心、剂量递增试验中，年龄在 10 至 22 岁的健康参与者接受了 1 剂 Tdap-1018 1500μg、Tdap-1018 3000μg 或 Boostrix。接种后 4 周评估针对百日咳（百日咳毒素、丝状血凝素、 pertactin）、破伤风和白喉抗原的抗体以及针对百日咳毒素的中和抗体的几何平均浓度（GMC）和增强反应率（BRR）。接种后 7 天内评估与注射相关的不良反应，并在接种后 12 周内评估未经报告的不良事件。在 117 名入组的参与者中，80 名成人（92%）和 30 名青少年（100%）完成了研究。两种 Tdap-1018 制剂均具有良好的耐受性，无疫苗相关严重不良事件。除 Tdap-1018 引起的中度疼痛比例较高外，与 Boostrix 相比，注射后反应的频率和严重程度相似。在第 4 周，3000μg 组所有抗原的 GMC 和 BRR 比值与 Boostrix 相似或更高，抗百日咳毒素（2.1[1.5-3.0]）和抗破伤风毒素（1.8[1.1-2.9]）的 GMC 比值显著更高，抗百日咳毒素（差异[95%CI]：34.5%[13.4-54.6%]）、抗 pertactin（19.2%[4.4-38.1%]）和抗破伤风毒素（30.0%[3.6-52.7%]）的 BRR 显著更高。对于青少年，在 3000μg 组中，所有抗原的 GMC 和 BRR 比值与 Boostrix 相似或更高。两种 Tdap-1018 制剂均具有可接受的安全性和耐受性。Tdap-1018 3000μg 诱导的免疫应答与 Boostrix 相似或更高。ACTRN12620001177943（澳大利亚和新西兰临床试验注册处；https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12620001177943p）。
