Efficacy, safety, and immunogenicity of the AS01E-adjuvanted respiratory syncytial virus prefusion F protein vaccine (RSVPreF3 OA) in older adults over three respiratory syncytial virus seasons (AReSVi-006): a multicentre, randomised, observer-blinded, placebo-controlled, phase 3 trial

IF 38.7 1区医学 Q1 CRITICAL CARE MEDICINE

Lancet Respiratory Medicine Pub Date : 2025-04-14 DOI:10.1016/s2213-2600(25)00048-7

Michael G Ison, Alberto Papi, Eugene Athan, Robert G Feldman, Joanne M Langley, Dong-Gun Lee, Isabel Leroux-Roels, Federico Martinon-Torres, Tino F Schwarz, Richard N van Zyl-Smit, Susanna Cuadripani, Quentin Deraedt, Nancy Dezutter, Catherine Gerard, Laurence Fissette, Stebin Xavier, Marie-Pierre David, Aurélie Olivier, Marie Van der Wielen, Dominique Descamps, Manuel Zocco

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引用次数: 0

Abstract

Background

Duration of protection after respiratory syncytial virus (RSV) vaccination is unknown. This study aimed to evaluate efficacy and safety over three RSV seasons of the AS01_E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) against RSV-related lower respiratory tract disease (RSV-LRTD) in older adults.

Methods

In this randomised, observer-blind, placebo-controlled, phase 3 trial (AReSVi-006), participants aged 60 years or older in 275 centres (ie, GP practices and clinical research sites) across 17 countries in Africa, Asia, Oceania, Europe, and North America were randomly assigned (1:1) to receive RSVPreF3 OA or placebo before RSV season one. RSVPreF3 OA recipients were re-randomly assigned (1:1) before RSV season two to receive a second RSVPreF3 OA dose (RSV revaccination group) or placebo (RSV single-dose group). Recipients of placebo before RSV season one also received placebo before season two (placebo group). The primary objective (efficacy against first occurrence of RSV-LRTD over one RSV season) was reported previously. Confirmatory secondary objectives were to demonstrate efficacy over three RSV seasons of a single RSVPreF3 OA dose and of a first dose followed by revaccination 1 year later, against RSV-LRTD, overall and by RSV subtype (success criteria: lower limits of two-sided CIs around efficacy estimates >20% [RSV-LRTD] and >0% [RSV-LRTD by RSV subtype]). This study is registered with ClinicalTrials.gov, NCT04886596, and is complete.

Findings

Participants were enrolled between May 25, 2021, and Jan 31, 2022. Efficacy analyses included 12 468 RSVPreF3 OA recipients and 12 498 placebo recipients. Cumulative efficacy over three seasons of one RSVPreF3 OA dose was 62·9% (97·5% CI 46·7–74·8) against RSV-LRTD, 69·8% (42·2–85·7) against RSV A-related LRTD, and 58·6% (35·9–74·1) against RSV B-related LRTD (median follow-up from day 15 post-dose one 30·6 months [IQR 26·2–32·0]). Efficacy was observed over three seasons among participants aged 60–69 years, participants aged 70–79 years, pre-frail participants (ie, those with a walking speed of 0·4–0·99 m/s in a gait speed test), and participants with pre-existing conditions that increase the RSV-LRTD risk. Efficacy against RSV-LRTD decreased over time. A first RSVPreF3 OA dose followed by revaccination 1 year later had an efficacy that was within the same range as that of one dose. RSVPreF3 OA showed a clinically acceptable safety profile. Between dose one and trial end, eight (<1%) participants in the RSV single-dose group, 12 (<1%) in the RSV revaccination group, and 12 (<1%) in the placebo group had a serious adverse event considered to be related to the trial intervention by the investigator. Five deaths were assessed as related to the trial intervention by the investigator: three in the vaccine groups (cardiopulmonary failure, cardiac arrest, and left ventricular failure) and two in the placebo group (death of unknown cause and pulmonary embolism).

Interpretation

A single RSVPreF3 OA dose was efficacious against RSV-LRTD over three RSV seasons in people aged 60 years or older, despite a decrease in efficacy over time. Further research is needed to establish the optimal revaccination strategy. These results support the favourable benefit–risk profile of RSVPreF3 OA to help protect against RSV-LRTD for at least three RSV seasons.

Funding

GSK.

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as01e佐剂呼吸道合胞病毒预融合F蛋白疫苗（rsvpref3oa）在老年人三个呼吸道合胞病毒季节（AReSVi-006）中的有效性、安全性和免疫原性：一项多中心、随机、观察者盲、安慰剂对照的3期试验

背景：呼吸道合胞病毒（RSV）疫苗接种后保护的持续时间尚不清楚。本研究旨在评估as01e佐剂RSV预融合F蛋白疫苗（RSVPreF3 OA）在三个RSV季节对老年人RSV相关下呼吸道疾病（RSV- lrtd）的有效性和安全性。在这项随机、观察者盲、安慰剂对照的3期试验（AReSVi-006）中，来自非洲、亚洲、大洋洲、欧洲和北美17个国家的275个中心（即全科医生诊所和临床研究站点）的60岁或以上的参与者被随机分配（1:1）接受RSV第一季前的RSVPreF3 OA或安慰剂治疗。在RSV第二季之前，RSVPreF3 OA接受者被重新随机分配（1:1），接受第二剂RSVPreF3 OA （RSV再接种组）或安慰剂（RSV单剂组）。RSV第一季前接受安慰剂治疗的患者也在第二季前接受安慰剂治疗（安慰剂组）。主要目标（在一个RSV季节内对首次发生RSV- lrtd的疗效）先前有报道。验证性次要目标是证明单剂RSVPreF3 OA和首次接种1年后再次接种的RSV- lrtd在三个RSV季节的有效性，针对RSV- lrtd，总体和RSV亚型（成功标准：双侧ci的下限，有效性估计为20% [RSV- lrtd]和0% [RSV- lrtd按RSV亚型]）。本研究已在ClinicalTrials.gov注册，编号NCT04886596，并且已经完成。研究人员在2021年5月25日至2022年1月31日期间招募了参与者。疗效分析包括12468名RSVPreF3 OA接受者和12498名安慰剂接受者。一剂RSVPreF3 OA三季累积疗效分别为抗RSV-LRTD的62.9% （97.5% CI 46.7 - 78.4）、抗RSV- a相关LRTD的69.8%（42.2 - 85.7）和抗RSV- b相关LRTD的58.6%(35.9 - 74.1)（中位随访时间为1剂后第15天30.6个月[IQR 26.2 - 32.6]）。在60-69岁、70-79岁、体弱前期（即在步态速度测试中行走速度为0.4 - 0.99 m/s）和存在RSV-LRTD风险增加的既往疾病参与者中，观察了三个季度的疗效。抗RSV-LRTD的疗效随着时间的推移而下降。首次接种RSVPreF3 OA疫苗，1年后再次接种，其疗效与一次接种相同。RSVPreF3 OA具有临床可接受的安全性。在剂量1至试验结束之间，RSV单剂量组有8名（<1%）参与者，RSV再接种组有12名（<1%）参与者，安慰剂组有12名（<1%）参与者发生了研究者认为与试验干预有关的严重不良事件。研究者评估了5例与试验干预相关的死亡：3例发生在疫苗组（心肺衰竭、心脏骤停和左心室衰竭），2例发生在安慰剂组（死因不明和肺栓塞）。在60岁或以上的人群中，单剂RSVPreF3 OA在三个RSV季节对RSV- lrtd有效，尽管随着时间的推移有效性会降低。需要进一步研究以确定最佳的再接种策略。这些结果支持了RSVPreF3 OA有利的收益-风险特征，有助于在至少三个RSV季节预防RSV- lrtd。

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来源期刊

Lancet Respiratory Medicine RESPIRATORY SYSTEM-RESPIRATORY SYSTEM

CiteScore

87.10

自引率

0.70%

发文量

572

期刊介绍： The Lancet Respiratory Medicine is a renowned journal specializing in respiratory medicine and critical care. Our publication features original research that aims to advocate for change or shed light on clinical practices in the field. Additionally, we provide informative reviews on various topics related to respiratory medicine and critical care, ensuring a comprehensive coverage of the subject. The journal covers a wide range of topics including but not limited to asthma, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), tobacco control, intensive care medicine, lung cancer, cystic fibrosis, pneumonia, sarcoidosis, sepsis, mesothelioma, sleep medicine, thoracic and reconstructive surgery, tuberculosis, palliative medicine, influenza, pulmonary hypertension, pulmonary vascular disease, and respiratory infections. By encompassing such a broad spectrum of subjects, we strive to address the diverse needs and interests of our readership.