epidemics persist as transmission remains unabated despite high acellular pertussis vaccination rates. BPZE1, a live attenuated intranasal pertussis vaccine, was designed to prevent infection and disease. We aimed to assess the immunogenicity and safety of BPZE1 compared with the tetanus–diphtheria–acellular pertussis vaccine (Tdap). In this double-blind, phase 2b trial at three research centres in the USA, healthy adults aged 18–50 years were randomly assigned (2:2:1:1) via a permuted block randomisation schedule to receive BPZE1 vaccination followed by BPZE1 attenuated challenge, BPZE1 vaccination followed by placebo challenge, Tdap followed by BPZE1 attenuated challenge, or Tdap followed by placebo challenge. On day 1, lyophilised BPZE1 was reconstituted with sterile water and given intranasally (0·4 mL delivered to each nostril), whereas Tdap was given intramuscularly. To maintain masking, participants in the BPZE1 groups received an intramuscular saline injection, and those in the Tdap groups received intranasal lyophilised placebo buffer. The attenuated challenge took place on day 85. The primary immunogenicity endpoint was the proportion of participants achieving nasal secretory IgA seroconversion against at least one antigen on day 29 or day 113. Reactogenicity was assessed up to 7 days after vaccination and challenge, and adverse events were recorded for 28 days after vaccination and challenge. Serious adverse events were monitored throughout the study. This trial is registered with , . Between June 17 and Oct 3, 2019, 458 participants were screened and 280 were randomly assigned to the main cohort: 92 to the BPZE1–BPZE1 group, 92 to the BPZE1–placebo group, 46 to the Tdap–BPZE1 group, and 50 to the Tdap–placebo group. Seroconversion of at least one specific nasal secretory IgA was recorded in 79 (94% [95% CI 87–98]) of 84 participants in the BPZE1–BPZE1 group, 89 (95% [88–98]) of 94 in the BPZE1–placebo group, 38 (90% [77–97]) of 42 in the Tdap–BPZE1 group, and 42 (93% [82–99]) of 45 in the Tdap–placebo group. BPZE1 induced broad and consistent -specific mucosal secretory IgA responses, whereas Tdap did not induce consistent mucosal secretory IgA responses. Both vaccines were well tolerated, with mild reactogenicity and no serious adverse events related to study vaccination. BPZE1 induced nasal mucosal immunity and produced functional serum responses. BPZE1 has the potential to avert infections, which ultimately could lead to reduced transmission and diminished epidemic cycles. These results should be confirmed in large phase 3 trials. ILiAD Biotechnologies.

中文翻译：

---

BPZE1（一种鼻内减毒百日咳活疫苗）与破伤风-白喉-无细胞百日咳疫苗的免疫原性和安全性：一项随机、双盲、2b 期试验

尽管无细胞百日咳疫苗接种率很高，但传播仍然有增无减，流行病持续存在。BPZE1 是一种鼻内百日咳减毒活疫苗，旨在预防感染和疾病。我们的目的是评估 BPZE1 与破伤风白喉无细胞百日咳疫苗 (Tdap) 相比的免疫原性和安全性。在美国三个研究中心进行的这项双盲 2b 期试验中，18-50 岁的健康成年人通过置换分组随机化时间表被随机分配 (2:2:1:1) 接受 BPZE1 疫苗接种，然后接种 BPZE1 减毒疫苗攻击，BPZE1 疫苗接种后进行安慰剂攻击，Tdap 后进行 BPZE1 弱毒攻击，或 Tdap 后进行安慰剂攻击。第1天，用无菌水重构冻干的BPZE1并鼻内给药（0·4mL递送至每个鼻孔），而Tdap则肌内给药。为了维持掩蔽，BPZE1 组的参与者接受了肌内盐水注射，Tdap 组的参与者接受了鼻内冻干安慰剂缓冲液。减毒攻击发生在第 85 天。主要免疫原性终点是在第 29 天或第 113 天实现针对至少一种抗原的鼻分泌型 IgA 血清转化的参与者的比例。在疫苗接种和攻击后 7 天评估反应原性以及不良事件在接种疫苗和攻击后记录28天。在整个研究过程中对严重不良事件进行监测。该试验已在 , 注册。2019 年 6 月 17 日至 10 月 3 日期间，对 458 名参与者进行了筛查，其中 280 名被随机分配到主要队列：92 名被分配到 BPZE1-BPZE1 组，92 名被分配到 BPZE1-安慰剂组，46 名被分配到 Tdap-BPZE1 组，50 名被分配到 Tdap-BPZE1 组。 Tdap-安慰剂组。BPZE1-BPZE1 组 84 名参与者中有 79 名（94% [95% CI 87-98]）记录到至少一种特定鼻分泌性 IgA 的血清转化，BPZE1 组 94 名参与者中有 89 名（95% [88-98]） –安慰剂组，Tdap-BPZE1 组 42 人中有 38 人（90% [77-97]），Tdap-安慰剂组 45 人中有 42 人（93% [82-99]）。BPZE1诱导广泛且一致的特异性粘膜分泌性IgA反应，而Tdap不诱导一致的粘膜分泌性IgA反应。两种疫苗均具有良好的耐受性，具有轻微的反应原性，并且没有与研究疫苗接种相关的严重不良事件。BPZE1 诱导鼻粘膜免疫并产生功能性血清反应。BPZE1 有可能避免感染，最终可能导致传播减少和流行周期缩短。这些结果应该在大型 3 期试验中得到证实。ILiAD 生物技术。