Arbetter Doug, Gopalakrishnan Vancheswaran, Aksyuk Anastasia A, Ahani Bahar, Chang Yue, Dagan Ron, Esser Mark T, Hammitt Laura L, Mankad Vaishali S, Saez-Llorens Xavier, Shen David, Leach Amanda, Kelly Elizabeth J, Villafana Tonya, Wilkins Deidre
Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Boston, MA, USA.
Bioinformatics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Clin Infect Dis. 2024 Dec 4. doi: 10.1093/cid/ciae596.
Nirsevimab is an extended half-life, highly potent neutralizing monoclonal antibody against the respiratory syncytial virus (RSV) fusion protein, with efficacy in preventing RSV-associated medically attended (MA) lower respiratory tract infection (LRTI) in infants and medically vulnerable children (aged ≤24 months). This post-hoc exploratory analysis examined the incidence of LRTI from RSV and other respiratory pathogens during a 2:1 randomized, double-blind, placebo-controlled, phase 3 study of nirsevimab, in healthy-term and late-preterm (i.e. gestational age ≥35 weeks) infants entering their first RSV season (MELODY).
3012 participants were randomized to nirsevimab (n = 2009) or placebo (n = 1003). Nasopharyngeal swabs were collected from infants presenting with an LRTI and tested for 22 different respiratory pathogens using the BioFire® Respiratory 2.1 Panel. Incidence of RSV and non-RSV MA-LRTIs through Day 511 and LRTI severity per the ReSViNET scale were assessed.
852 nasopharyngeal swabs were collected from 561 participants through Day 511: 519 swabs from 337 nirsevimab participants and 333 swabs from 224 placebo participants. RSV and non-RSV infections were detected in 193/852 (22.7%) and 551/852 (64.7%) swabs, respectively. RSV infection rates were lower with nirsevimab compared with placebo, including RSV-rhinovirus/enterovirus coinfections. Rates of other viral infections were similar between study arms. Approximately 70% of single RSV infections and RSV coinfections were adjudicated as mild, and 26.2% of single RSV infections and 24.5% of RSV coinfections required hospitalization.
Nirsevimab protected against RSV single and coinfections, with no evidence of replacement of RSV with other respiratory viruses.
ClinicalTrials.gov NCT03979313.
尼塞韦单抗是一种半衰期延长、高效的抗呼吸道合胞病毒（RSV）融合蛋白的中和单克隆抗体，在预防婴儿和医学上易感染儿童（年龄≤24个月）的RSV相关的需要就医（MA）的下呼吸道感染（LRTI）方面具有疗效。这项事后探索性分析在一项针对进入首个RSV季节的足月儿和晚期早产儿（即胎龄≥35周）的尼塞韦单抗2:1随机、双盲、安慰剂对照3期研究（MELODY）中，考察了RSV和其他呼吸道病原体导致的LRTI发病率。
3012名参与者被随机分配至尼塞韦单抗组（n = 2009）或安慰剂组（n = 1003）。从出现LRTI的婴儿中采集鼻咽拭子，并使用BioFire® Respiratory 2.1 Panel检测22种不同的呼吸道病原体。评估至第511天RSV和非RSV MA-LRTI的发病率以及根据ReSViNET量表评估的LRTI严重程度。
至第511天，从561名参与者中采集了852份鼻咽拭子：337名尼塞韦单抗参与者的519份拭子和224名安慰剂参与者的333份拭子。在193/852（22.7%）和551/852（64.7%）份拭子中分别检测到RSV和非RSV感染。与安慰剂相比，尼塞韦单抗组的RSV感染率较低，包括RSV-鼻病毒/肠道病毒合并感染。研究组之间其他病毒感染率相似。约70%的单一RSV感染和RSV合并感染被判定为轻度，26.2%的单一RSV感染和24.5%的RSV合并感染需要住院治疗。
尼塞韦单抗可预防RSV单一感染和合并感染，没有证据表明RSV会被其他呼吸道病毒替代。
ClinicalTrials.gov NCT03979313。
