一种二价呼吸道合胞病毒预融合F疫苗在老年人中的疗效和安全性

Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults.

作者信息

Walsh Edward E, Pérez Marc Gonzalo, Zareba Agnieszka M, Falsey Ann R, Jiang Qin, Patton Michael, Polack Fernando P, Llapur Conrado, Doreski Pablo A, Ilangovan Kumar, Rämet Mika, Fukushima Yasushi, Hussen Nazreen, Bont Louis J, Cardona Jose, DeHaan Elliot, Castillo Villa Giselle, Ingilizova Marinela, Eiras Daniel, Mikati Tarek, Shah Rupal N, Schneider Katherine, Cooper David, Koury Kenneth, Lino Maria-Maddalena, Anderson Annaliesa S, Jansen Kathrin U, Swanson Kena A, Gurtman Alejandra, Gruber William C, Schmoele-Thoma Beate

机构信息

From the University of Rochester Medical Center, Rochester (E.E.W., A.R.F.), and Vaccine Research and Development (E.D., G.C.V., M.I., D.E., T.M., R.N.S., K.S., D.C., K.K., K.U.J., K.A.S., A.G., W.C.G.) and Worldwide Research, Development, and Medical (A.S.A.), Pfizer, Pearl River - both in New York; iTrials-Hospital Militar Central (G.P.M.), Fundación INFANT (F.P.P.), and Fundación Respirar Clinical Research Unit (P.A.D.), Buenos Aires, and Clinica Mayo de Urgencias Médicas Cruz Blanca, San Miguel de Tucumán (C.L.) - all in Argentina; Vaccine Research and Development, Pfizer, Collegeville, PA (A.M.Z., Q.J.); Vaccine Research and Development, Pfizer, Hurley, United Kingdom (M.P.); Vaccine Research and Development, Pfizer, Raleigh, NC (K.I.); Faculty of Medicine and Health Technology, Tampere University, and Finnish Vaccine Research - both in Tampere, Finland (M.R.); Fukuwa Clinic, Tokyo (Y.F.); Netcare Lakeview Hospital, Benoni, South Africa (N.H.); the Departments of Pediatrics and Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, and Respiratory Syncytial Virus Network Foundation, Zeist - both in the Netherlands (L.J.B.); Indago Research and Health Center, Hialeah, FL (J.C.); Worldwide Safety, Pfizer, Milan (M.-M.L.); and Vaccine Research and Development, Pfizer Pharma, Berlin (B.S.-T.).

出版信息

N Engl J Med. 2023 Apr 20;388(16):1465-1477. doi: 10.1056/NEJMoa2213836. Epub 2023 Apr 5.

DOI:10.1056/NEJMoa2213836

PMID:37018468

Abstract

BACKGROUND

Respiratory syncytial virus (RSV) infection causes considerable illness in older adults. The efficacy and safety of an investigational bivalent RSV prefusion F protein-based (RSVpreF) vaccine in this population are unknown.

METHODS

In this ongoing, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults (≥60 years of age) to receive a single intramuscular injection of RSVpreF vaccine at a dose of 120 μg (RSV subgroups A and B, 60 μg each) or placebo. The two primary end points were vaccine efficacy against seasonal RSV-associated lower respiratory tract illness with at least two or at least three signs or symptoms. The secondary end point was vaccine efficacy against RSV-associated acute respiratory illness.

RESULTS

At the interim analysis (data-cutoff date, July 14, 2022), 34,284 participants had received RSVpreF vaccine (17,215 participants) or placebo (17,069 participants). RSV-associated lower respiratory tract illness with at least two signs or symptoms occurred in 11 participants in the vaccine group (1.19 cases per 1000 person-years of observation) and 33 participants in the placebo group (3.58 cases per 1000 person-years of observation) (vaccine efficacy, 66.7%; 96.66% confidence interval [CI], 28.8 to 85.8); 2 cases (0.22 cases per 1000 person-years of observation) and 14 cases (1.52 cases per 1000 person-years of observation), respectively, occurred with at least three signs or symptoms (vaccine efficacy, 85.7%; 96.66% CI, 32.0 to 98.7). RSV-associated acute respiratory illness occurred in 22 participants in the vaccine group (2.38 cases per 1000 person-years of observation) and 58 participants in the placebo group (6.30 cases per 1000 person-years of observation) (vaccine efficacy, 62.1%; 95% CI, 37.1 to 77.9). The incidence of local reactions was higher with vaccine (12%) than with placebo (7%); the incidences of systemic events were similar (27% and 26%, respectively). Similar rates of adverse events through 1 month after injection were reported (vaccine, 9.0%; placebo, 8.5%), with 1.4% and 1.0%, respectively, considered by the investigators to be injection-related. Severe or life-threatening adverse events were reported in 0.5% of vaccine recipients and 0.4% of placebo recipients. Serious adverse events were reported in 2.3% of participants in each group through the data-cutoff date.

CONCLUSIONS

RSVpreF vaccine prevented RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness in adults (≥60 years of age), without evident safety concerns. (Funded by Pfizer; RENOIR ClinicalTrials.gov number, NCT05035212; EudraCT number, 2021-003693-31.).

摘要

背景

呼吸道合胞病毒（RSV）感染在老年人中可导致相当严重的疾病。一种基于RSV前融合F蛋白的二价研究性疫苗（RSVpreF）在该人群中的疗效和安全性尚不清楚。

方法

在这项正在进行的3期试验中，我们以1:1的比例将成年人（≥60岁）随机分配，分别接受一次剂量为120μg（A和B两个RSV亚组各60μg）的RSVpreF疫苗肌肉注射或安慰剂。两个主要终点是针对季节性RSV相关下呼吸道疾病且伴有至少两种或至少三种体征或症状的疫苗效力。次要终点是针对RSV相关急性呼吸道疾病的疫苗效力。

结果

在中期分析（数据截止日期为2022年7月14日）时，34284名参与者接受了RSVpreF疫苗（17215名参与者）或安慰剂（17069名参与者）。疫苗组有11名参与者发生了伴有至少两种体征或症状的RSV相关下呼吸道疾病（每1000人年观察期内1.19例），安慰剂组有33名参与者发生（每1000人年观察期内3.58例）（疫苗效力，66.7%；96.66%置信区间[CI]，28.8至85.8）；分别有2例（每1000人年观察期内0.22例）和14例（每1000人年观察期内1.52例）发生了伴有至少三种体征或症状的情况（疫苗效力，85.7%；96.66%CI，32.0至98.7）。疫苗组有22名参与者发生了RSV相关急性呼吸道疾病（每1000人年观察期内2.38例），安慰剂组有58名参与者发生（每1000人年观察期内6.30例）（疫苗效力，62.1%；95%CI，37.1至77.9）。疫苗组局部反应的发生率（12%）高于安慰剂组（7%）；全身事件的发生率相似（分别为27%和26%）。报告的注射后1个月内不良事件发生率相似（疫苗组为9.0%，安慰剂组为8.5%），研究者认为分别有1.4%和1.0%与注射相关。0.5%的疫苗接种者和0.4%的安慰剂接受者报告了严重或危及生命的不良事件。截至数据截止日期，每组2.3%的参与者报告了严重不良事件。