Ad26.RSV.preF–RSV preF protein showed 80·0% vaccine efficacy against respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in older adults during one RSV season. No RSV vaccines have shown three-season efficacy. We aimed to evaluate efficacy of Ad26.RSV.preF–RSV preF protein over three RSV seasons. CYPRESS was a randomised, double-blind, placebo-controlled, phase 2b study done at 40 US clinical research centres wherein adults aged 65 years or older were centrally randomly assigned 1:1 by computer algorithm to receive Ad26.RSV.preF–RSV preF protein or placebo (one intramuscular injection) on day 1. Investigators, participants, site personnel, and the sponsor were masked to vaccine allocation, except for individuals involved in preparation of study vaccinations. The primary endpoint (first occurrence of RSV-mediated LRTD meeting one of three case definitions) was previously reported. Here, the predefined exploratory endpoint of vaccine efficacy against RSV-positive LRTD was assessed in the per-protocol efficacy set (all participants randomly assigned and vaccinated without protocol deviations affecting efficacy) through season 1 and from day 365 until the end of season 3. Humoral and cellular immunogenicity was assessed in a subset of randomly assigned and vaccinated participants. The secondary endpoint of safety through the first RSV season was previously reported; follow-up for selected safety outcomes (fatal adverse events, adverse events leading to study discontinuation, serious adverse events, and vaccine-related serious adverse events) until study completion is reported here in all randomly assigned and vaccinated participants. This trial is registered with , and is complete. Of 6672 adults screened, 5782 participants (2891 each receiving vaccine or placebo) were enrolled and vaccinated between Aug 5 and Nov 13, 2019. The season 2 per-protocol efficacy set included 2124 vaccine recipients and 2126 placebo recipients (season 3: 864 and 881; across three seasons: 2795 and 2803, respectively). Vaccine efficacy against RSV LRTD was 76·1% (95% CI 26·9–94·2) over seasons 2 and 3 and 78·7% (57·3–90·4) across three seasons. For those in the immunogenicity subset (vaccine n=97; placebo n=98), immune responses remained above baseline for at least 1 year. Serious adverse events occurred in 47 (2·1%) and 12 (1·3%) vaccine recipients and 45 (2·1%) and 10 (1·1%) placebo recipients during seasons 2 and 3, respectively. No treatment-related serious or fatal adverse events were reported. Ad26.RSV.preF–RSV preF protein maintained high efficacy against RSV LRTD in older adults across three RSV seasons. Janssen Vaccines & Prevention.

中文翻译：

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Ad26.RSV.preF–RSV preF 蛋白疫苗 (CYPRESS) 的长期功效和免疫原性：一项随机、双盲、安慰剂对照 2b 期研究


Ad26.RSV.preF–RSV preF 蛋白在一个 RSV 季节期间对老年人呼吸道合胞病毒 (RSV) 下呼吸道疾病 (LRTD) 表现出 80·0% 的疫苗效力。没有 RSV 疫苗显示出三个季节的功效。我们的目的是评估 Ad26.RSV.preF–RSV preF 蛋白在三个 RSV 季节中的功效。 CYPRESS 是一项在 40 个美国临床研究中心进行的随机、双盲、安慰剂对照 2b 期研究，其中 65 岁或以上的成年人通过计算机算法以 1:1 的比例集中随机分配接受 Ad26.RSV.preF–RSV preF第一天注射蛋白质或安慰剂（一次肌肉注射）。除参与准备研究疫苗接种的个人外，研究人员、参与者、现场工作人员和申办者均不了解疫苗分配情况。主要终点（RSV 介导的 LRTD 首次出现符合三个病例定义之一）先前已报告。在这里，在第 1 季以及从第 365 天到第 3 季结束期间，在符合方案的功效集中评估了针对 RSV 阳性 LRTD 的疫苗功效的预定义探索性终点（所有参与者随机分配并接种疫苗，没有影响功效的方案偏差）。在随机分配和接种疫苗的参与者子集中评估了体液和细胞免疫原性。先前报告了第一个 RSV 季节的次要安全终点；对选定的安全结果（致命不良事件、导致研究中止的不良事件、严重不良事件以及与疫苗相关的严重不良事件）进行随访，直到在所有随机分配和接种疫苗的参与者中报告研究完成。该试验已在 注册，并已完成。 在 6672 名接受筛查的成年人中，有 5782 名参与者（每人 2891 名接受疫苗或安慰剂）在 2019 年 8 月 5 日至 11 月 13 日期间登记并接种了疫苗。第二季每个方案的功效集包括 2124 名疫苗接受者和 2126 名安慰剂接受者（第三季：864 名和 2126 名安慰剂接受者）。 881；三个季节分别为 2795 和 2803）。针对 RSV LRTD 的疫苗功效在第 2 季和第 3 季为 76·1% (95% CI 26·9–94·2)，在三个季节中为 78·7% (57·3–90·4)。对于免疫原性子集（疫苗 n=97；安慰剂 n=98）中的患者，免疫反应在至少一年内保持在基线以上。在第 2 季和第 3 季期间，分别有 47 名 (2·1%) 和 12 名 (1·3%) 疫苗接受者以及 45 名 (2·1%) 和 10 名 (1·1%) 安慰剂接受者发生严重不良事件。没有报告与治疗相关的严重或致命不良事件。 Ad26.RSV.preF–RSV preF 蛋白在三个 RSV 季节中对老年人中的 RSV LRTD 保持高效。杨森疫苗和预防。