Background This study investigated the safety, reactogenicity, and immunogenicity in healthy subjects of a Clostridioides difficile vaccine candidate with/without adjuvant, targeting toxins A and B. Methods In this first-in-human, phase 1, observer-blind study, subjects aged 18–45 years were randomized to receive F2 antigen (n = 10) or placebo (n = 10), and subjects aged 50–70 years to receive F2 antigen plus AS01 adjuvant (n = 45), F2 antigen (n = 45), or placebo (n = 30) in 2 doses 1 month apart. A subcohort (n = 40) received a third dose 15 months later. Solicited adverse events (AEs) were recorded for 7 days and unsolicited AEs for 30 days after each dose. Immunogenicity was assessed at baseline and after each dose. Results Solicited AEs were transient and most frequent in subjects receiving F2 antigen plus AS01. No serious AEs were considered related to study vaccine. Immunogenicity was substantially higher in subjects receiving F2 antigen plus AS01 than subjects receiving F2 antigen alone. A third dose increased the immune response in subjects with baseline neutralization titers below the assay lower limit of quantitation. Conclusions The GSK C. difficile vaccine candidate was immunogenic, especially when given with AS01, and was well tolerated with an acceptable safety profile. Clinical Trial Registration NCT04026009.

中文翻译：

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健康成人艰难梭菌候选佐剂疫苗的安全性和免疫原性：一项随机安慰剂对照 1 期研究


背景 本研究调查了针对毒素 A 和 B 的艰难梭菌候选疫苗在有/没有佐剂的情况下在健康受试者中的安全性、反应原性和免疫原性。方法 在这项首次人体 1 期观察者盲法研究中，18-45 岁的受试者被随机分配接受 F2 抗原 （n = 10） 或安慰剂 （n = 10），50-70 岁的受试者接受 F2 抗原加 AS01 佐剂 （n = 45）， F2 抗原 （n = 45） 或安慰剂 （n = 30） 分 2 剂，间隔 1 个月。一个亚组 （n = 40） 在 15 个月后接受了第三剂。每次给药后 7 天记录主动不良事件 （AEs），记录主动不良事件 （AEs） 30 天。在基线和每次给药后评估免疫原性。结果 请求的 AE 是短暂的，在接受 F2 抗原加 AS01 的受试者中最为常见。没有严重的 AE 被认为与研究疫苗有关。接受 F2 抗原加 AS01 的受试者的免疫原性显著高于单独接受 F2 抗原的受试者。第三剂增加了基线中和滴度低于测定定量下限的受试者的免疫反应。结论 GSK 艰难拟梭菌候选疫苗具有免疫原性，尤其是与 AS01 一起接种时，耐受性良好，安全性可接受。临床试验注册 NCT04026009。