呼吸道合胞病毒的遗传变异及其对单克隆抗体结合位点的影响：一项2023-2024年季节的全国横断面研究

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-09-24 DOI:10.1016/j.intimp.2025.115591

Antonio Piralla , Greta Romano , Carla Acciarri , Stefano Menzo , Sara Uceda Renteria , Annapaola Callegaro , Cristina Galli , Laura Pellegrinelli , Alessandra Pierangeli , Matteo Fracella , Federica Novazzi , Nicasio Mancini , Cristina Russo , Stefania Ranno , Elisa Vian , Donna Damian , Elisabetta Pagani , Elisa Masi , Elena Pomari , Concetta Castilletti , Elena Pariani

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引用次数: 0

摘要

背景：呼吸道合胞病毒是全球急性下呼吸道感染的主要原因。随着疫苗和单克隆抗体等预防工具开始进入临床使用，基线基因组数据对于评估其未来影响和检测潜在的耐药性相关突变至关重要。呼吸道病毒感染工作组（GLIViRe）开展了这项多中心研究，以表征2023-2024年季节在意大利传播的RSV的遗传谱，这是在引入免疫预防干预措施之前。该研究的重点是鉴定palivizumab、nirsevimab、RSM01、TNM-001和clesrovimab单抗结合位点F蛋白的突变。方法：选取意大利15个实验室在2023-2024年流感样疾病（ILI）或急性呼吸道感染（ARI）患者中采集的350份RSV阳性呼吸道样本进行序列分析。采用Sanger或下一代测序对287份RSV-A和63份RSV-B样本进行F基因测序。使用IQ-TREE进行系统发育分析，并通过NextStrain整合全球数据。使用ChimeraX和protein Data Bank模型将关键突变映射到F蛋白结构上。香农熵用于评估氨基酸变异。结果：RSV-A主要属于新兴的A.D、A.D 1和A.D 3支系，RSV-B主要聚集在B·D支系。在抗原性位点∅处检测到关键替换，特别是在nirsevimab和RSM01界面处。帕利珠单抗/TNM-001 II位点未发生变化。所有感兴趣的突变都暴露在F蛋白表面。结论：在引入疫苗和单克隆抗体之前，本研究提供了意大利RSV的关键基因组快照。持续监测对于监测病毒演变和支持未来免疫战略的长期有效性至关重要。

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Genetic variability of respiratory syncytial virus and its impact on monoclonal antibody binding sites: a national cross-sectional study during the 2023–2024 season

Background

Respiratory syncytial virus is a primary cause of acute lower respiratory tract infections globally. As preventive tools such as vaccines and monoclonal antibodies begin to enter clinical use, baseline genomic data are critical to evaluate their future impact and detect potential resistance-related mutations. The working group on respiratory viral infections (GLIViRe) conducted this multicenter study to characterize the genetic profile of RSV circulating in Italy during the 2023–2024 season, immediately prior to the introduction of immunoprophylactic interventions. The study focused on identifying mutations in the F protein at mAb binding sites for palivizumab, nirsevimab, RSM01, TNM-001, and clesrovimab.

Methods

A total of 350 respiratory samples positive for RSV collected from patients with influenza-like illness (ILI) or acute respiratory infection (ARI), during the 2023–2024 season from 15 Italian laboratories were selected for sequence analysis. The F gene sequencing was performed on 287 RSV-A and 63 RSV-B samples using Sanger or next-generation sequencing. Phylogenetic analysis was conducted using IQ-TREE, with the integration of global data via NextStrain. Key mutations were mapped onto the F protein structure using ChimeraX and Protein Data Bank models. Shannon entropy was used to assess amino acid variability.

Results

RSV-A samples predominantly belonged to the emerging A.D, A.D.1, and A.D.3 clades, while RSV-B samples mainly clustered in the B·D lineage. Key substitutions were detected at antigenic site ∅, particularly at the nirsevimab and RSM01 interfaces. No changes occurred at the palivizumab/TNM-001 site II. All mutations of interest were exposed to the F protein surface.

Conclusions

This study provides a critical genomic snapshot of RSV in Italy prior to the introduction of vaccines and mAbs. Continuous surveillance is essential for monitoring viral evolution and supporting the long-term effectiveness of future immunization strategies.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.