孕期接种二价融合前F疫苗预防婴儿呼吸道合胞病毒疾病
Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.
作者信息
Kampmann Beate, Madhi Shabir A, Munjal Iona, Simões Eric A F, Pahud Barbara A, Llapur Conrado, Baker Jeffrey, Pérez Marc Gonzalo, Radley David, Shittu Emma, Glanternik Julia, Snaggs Hasra, Baber James, Zachariah Philip, Barnabas Shaun L, Fausett Merlin, Adam Tyler, Perreras Nicole, Van Houten Marlies A, Kantele Anu, Huang Li-Min, Bont Louis J, Otsuki Takeo, Vargas Sergio L, Gullam Joanna, Tapiero Bruce, Stein Renato T, Polack Fernando P, Zar Heather J, Staerke Nina B, Duron Padilla María, Richmond Peter C, Koury Kenneth, Schneider Katherine, Kalinina Elena V, Cooper David, Jansen Kathrin U, Anderson Annaliesa S, Swanson Kena A, Gruber William C, Gurtman Alejandra
机构信息
From the Medical Research Council Unit the Gambia, London School of Hygiene and Tropical Medicine, Fajara, Gambia (B.K.); the Institute for International Health Charité, Universitätsmedizin, Berlin (B.K.); the South African Medical Research Council (MRC) Vaccines and Infectious Diseases Analytics Research Unit, Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg (S.A.M.), and Family Centre for Research with Ubuntu, Department of Paediatrics and Child Health, University of Stellenbosch (S.L.B.), and the Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, South African MRC Unit on Child and Adolescent Health, University of Cape Town (H.J.Z.), Cape Town - all in South Africa; Vaccine Research and Development, Pfizer, Pearl River, NY (I.M., B.A.P., D.R., J. Glanternik, H.S., P.Z., K.K., K.S., E.V.K., D.C., K.U.J., A.S.A., K.A.S., W.C.G., A.G.); Children's Hospital Colorado, Aurora (E.A.F.S.); Instituto de Maternidad y Ginecología Nuestra Señora de Las Mercedes, San Miguel de Tucumán (C.L.), and iTrials-Hospital Militar Central (G.P.M., F.P.P.) and iTrials (S.L.V.), Buenos Aires - all in Argentina; Clinical Research Prime, Idaho Falls, ID (J. Baker); Vaccine Research and Development, Pfizer, Hurley, United Kingdom (E.S.); Vaccine Clinical Research, Pfizer, Sydney, NSW (J. Baber), and the University of Western Australia School of Medicine, Vaccine Trials Group, Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, and Perth Children's Hospital, Nedlands, WA (P.C.R.) - all in Australia; Boeson Research, Missoula, MT (M.F.); Meridian Clinical Research, Hastings, NE (T.A.); Asian Hospital and Medical Center, Manila, Philippines (N.P.); the Department of Pediatrics, Spaarne Gasthuis, Haarlem and Hoofddorp (M.A.V.H.), and the Departments of Pediatrics and Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, and Respiratory Syncytial Virus Network Foundation, Zeist (L.J.B.) - all in the Netherlands; Meilahti Vaccine Research Center, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki (A.K.); National Taiwan University Hospital, Taipei (L.-M.H.); the Department of Obstetrics and Gynecology, Sendai City Hospital, Sendai, Japan (T.O.); the Institute of Biomedical Sciences, University of Chile School of Medicine, Santiago, Chile (S.L.V.); University of Otago and New Zealand Clinical Research - both in Christchurch, New Zealand (J. Gullam); Centre Hospitalier Universitaire Sainte-Justine, Montreal (B.T.); Hospital Moinhos de Vento and Pontifícia Universidade Católica do Rio Grande do Sul - both in Porto Alegre, Brazil (R.T.S.); the Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark (N.B.S.); and Arké Study Management Organization, Mexico City (M.D.P.).
出版信息
N Engl J Med. 2023 Apr 20;388(16):1451-1464. doi: 10.1056/NEJMoa2216480. Epub 2023 Apr 5.
BACKGROUND
Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain.
METHODS
In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points.
RESULTS
At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively).
CONCLUSIONS
RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).
背景
孕期接种疫苗能否减轻新生儿和婴儿呼吸道合胞病毒（RSV）相关下呼吸道疾病的负担尚不确定。
方法
在这项在18个国家开展的3期双盲试验中，我们将妊娠24至36周的孕妇按1:1比例随机分配，分别接受一次肌肉注射120μg基于RSV前融合F蛋白的二价RSV疫苗（RSVpreF）或安慰剂。两个主要疗效终点为出生后90、120、150和180天内就医的严重RSV相关下呼吸道疾病以及就医的RSV相关下呼吸道疾病。疫苗效力置信区间的下限（90天时为99.5%置信区间[CI]；之后各时间点为97.58%CI）大于20%被认为符合主要终点的疫苗效力成功标准。
结果
在本次预先设定的中期分析中，一个主要终点符合疫苗效力成功标准。总体而言，3682名孕产妇参与者接受了疫苗，3676名接受了安慰剂；分别对3570名和3558名婴儿进行了评估。疫苗组妇女所生婴儿中有6名在出生后90天内发生了就医的严重下呼吸道疾病，安慰剂组妇女所生婴儿中有33名发生了此类疾病（疫苗效力，81.8%；99.5%CI，40.6至96.3）；出生后180天内分别发生了19例和62例（疫苗效力，69.4%；97.58%CI，44.3至84.1）。疫苗组妇女所生婴儿中有24名在出生后90天内发生了就医的RSV相关下呼吸道疾病，安慰剂组妇女所生婴儿中有56名发生了此类疾病（疫苗效力，57.1%；99.5%CI，14.7至79.8）；这些结果未达到统计学成功标准。在孕产妇参与者以及24个月龄及以下的婴幼儿中未检测到安全信号。疫苗组（13.8%的妇女和37.1%的婴儿）和安慰剂组（分别为13.1%和34.5%）在注射后1个月内或出生后1个月内报告的不良事件发生率相似。
结论
孕期接种RSVpreF疫苗对婴儿就医的严重RSV相关下呼吸道疾病有效，且未发现安全问题。（由辉瑞公司资助；MATISSE临床试验注册号，NCT04424316。）
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