GSK, Siena, Italy.
GSK, Rixensart, Belgium.
Respir Res. 2022 May 4;23(1):114. doi: 10.1186/s12931-022-02019-4.
Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) infections are frequently associated with exacerbations of chronic obstructive pulmonary disease (COPD). Results were reported with a two-dose (0-2 months) schedule of an investigational AS01-adjuvanted NTHi-Mcat vaccine containing three surface proteins from NTHi and one from Mcat. We evaluated the safety and immunogenicity of three NTHi-Mcat vaccine doses administered in two different schedules to adults with a smoking history (≥ 10 pack-years), immunologically representing the COPD population.
In this 18-month, randomised (1:1), observer-blind study with 6-month open follow-up, 200 healthy adults aged 40-80 years received NTHi-Mcat vaccine at 0-2-6 months and placebo at 12 months (0-2-6 group), or vaccine at 0-2-12 months and placebo at 6 months (0-2-12 group). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days, respectively, post-vaccination, and potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) throughout the study. Immune responses were assessed.
No safety concerns were identified with the third vaccine dose or overall. Most solicited AEs were mild/moderate. Unsolicited AEs were reported in 16%, 16.1% and 14.4% of participants in the 0-2-6 group post-dose 1, 2 and 3, respectively, and 20%, 20.4% and 9.7%, respectively, in the 0-2-12 group. In 24 months, SAEs were reported in 12 participants in the 0-2-6 group and 9 in the 0-2-12 group (18 events in each group). There were three deaths (unknown cause, 0-2-6 group; myocardial infarction, lung cancer in 0-2-12 group). pIMDs were reported in three participants in the 0-2-6 group (non-serious inflammatory bowel disease, gout, psoriasis) and three in the 0-2-12 group (serious ulcerative colitis, two with non-serious gout). The SAEs, deaths and pIMDs were considered not causally related to vaccination. Antigen-specific antibody concentrations were higher at 12 months post-dose 1 with the 0-2-6 schedule than with the 0-2-12 schedule and at 12 months post-dose 3 were similar between schedules, remaining higher than baseline.
No safety concerns were identified when the investigational NTHi-Mcat vaccine was administered via a 0-2-6 months or 0-2-12 months schedule to older adults with a smoking history. Persistent immune responses were observed after the third vaccine dose. Trial registration https://clinicaltrials.gov/ ; NCT03443427, registered February 23, 2018.
非分型流感嗜血杆菌（NTHi）和卡他莫拉菌（Mcat）感染常与慢性阻塞性肺疾病（COPD）加重有关。报道了一种含 NTHi 三种表面蛋白和 Mcat 一种表面蛋白的研究性 AS01 佐剂 NTHi-Mcat 疫苗的两剂（0-2 个月）方案的结果。我们评估了三剂 NTHi-Mcat 疫苗在两种不同方案下用于具有吸烟史（≥10 包年）的成年人群中的安全性和免疫原性，免疫上代表 COPD 人群。
在这项为期 18 个月、随机（1:1）、观察者盲法研究中，6 个月的开放性随访，200 名 40-80 岁的健康成年人在 0-2-6 个月时接受 NTHi-Mcat 疫苗和 12 个月时接受安慰剂（0-2-6 组），或在 0-2-12 个月时接受疫苗和 6 个月时接受安慰剂（0-2-12 组）。接种疫苗后分别在 7 天和 30 天内记录了疫苗接种后的不良反应（AE）和非预期性免疫介导疾病（pIMD）及严重不良事件（SAE）。评估了免疫反应。
未发现第三剂疫苗或总体安全性问题。大多数不良反应为轻度/中度。0-2-6 组中，分别有 16%、16.1%和 14.4%的参与者在接种第 1、2 和 3 剂后报告了非预期性不良反应，0-2-12 组中，分别有 20%、20.4%和 9.7%的参与者报告了非预期性不良反应。在 24 个月时，0-2-6 组中有 12 名参与者和 0-2-12 组中有 9 名参与者报告了 SAE（每组各有 18 例事件）。有 3 例死亡（0-2-6 组原因不明；0-2-12 组心肌梗死，肺癌）。0-2-6 组中有 3 名参与者报告了 pIMD（非严重炎症性肠病、痛风、银屑病），0-2-12 组中有 3 名参与者报告了 pIMD（严重溃疡性结肠炎，其中 2 例伴有非严重痛风）。SAE、死亡和 pIMD 被认为与疫苗接种无关。与 0-2-12 方案相比，0-2-6 方案接种第 1 剂后 12 个月时抗原特异性抗体浓度更高，接种第 3 剂后 12 个月时两种方案的浓度相似，且均高于基线。
对于具有吸烟史的老年患者，0-2-6 个月或 0-2-12 个月的研究性 NTHi-Mcat 疫苗接种方案未发现安全性问题。第三剂疫苗接种后可观察到持续的免疫反应。
