使用人体激发模型了解上呼吸道感染与呼吸道合胞病毒和肺炎链球菌的相互作用：一项多中心、随机对照研究方案。
Understanding the interaction of upper respiratory tract infection with respiratory syncytial virus and Streptococcus pneumoniae using a human challenge model: a multicenter, randomized controlled study protocol.
作者信息
Brito-Mutunayagam Sanjita, Hamilton David O, Mitsi Elena, Solórzano Carla, Li Grace, Rocha De Macedo Bruno, Elterish Filora, Liu Xinxue, Tanha Kiarash, White Rachel, Hyder-Wright Angela, Patel Bhumika, Urban Britta C, Whelan Conor, Trari Belhadef Hanane, Robinson Hannah, Plested Emma, Thompson Amber, Lahuerta Maria, Kanevsky Isis, Swanson Kena, Aliabadi Negar, Catusse Julie, Theilacker Christian, Gessner Bradford D, Mazur Natalie I, Chiu Christopher, Collins Andrea M, Morton Ben, Ramasamy Maheshi N, Ferreira Daniela M
机构信息
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
出版信息
PLoS One. 2025 Jul 1;20(7):e0325149. doi: 10.1371/journal.pone.0325149. eCollection 2025.
BACKGROUND
Streptococcus pneumoniae (pneumococcus) and respiratory syncytial virus (RSV) are major causes of respiratory infections globally. Viral and bacterial co-infections are commonly observed in respiratory infections and there is evidence that these pathogens interact synergistically to evade host responses and lead to more severe disease. Notably, RSV seasonal outbreaks are associated with increased hospitalization and a subsequent peak in invasive pneumococcal disease cases, particularly in pediatric populations. Here, we summarize a protocol for a controlled human infection model aiming to evaluate pathogen interaction dynamics and immune responses in a combined pneumococcus and RSV model. The primary objective is to determine whether primary RSV challenge increases the risk of secondary pneumococcal colonization.
METHODS
This is an open-label, multi-center, randomized controlled human co-infection study, inclusive of a pilot phase. Individuals will be randomized to primary inoculation with either pneumococcus (serotype 6B) or RSV (subtype RSV-A) intra-nasally on day 0 followed by a reciprocal challenge on day 7. During pilot phase A up to 10 participants will be monitored in an in-patient facility for 7-10 days following RSV-A challenge. If there are no safety concerns, we will then progress to an outpatient phase where participants will self-isolate at home. Clinical samples to be taken from participants include nasal swabs and washes for pathogen detection; and nasal cells, nasal lining fluid, and blood samples to examine mucosal and systemic immune responses.
DISCUSSION
This work will lead to important scientific knowledge on the interaction and dynamics between pneumococcus and RSV. This knowledge could help inform pneumococcal and RSV vaccination strategies, particularly for groups at risk of developing severe pneumococcal and RSV disease.
TRIAL REGISTRATION
The study is registered on ISRCTN (The UKs Clinical Study Registry). DOI https://doi.org/10.1186/ISRCTN12036902.
背景
肺炎链球菌（肺炎球菌）和呼吸道合胞病毒（RSV）是全球呼吸道感染的主要病因。病毒和细菌合并感染在呼吸道感染中很常见，并且有证据表明这些病原体相互协同作用以逃避宿主反应并导致更严重的疾病。值得注意的是，RSV季节性暴发与住院率增加以及随后侵袭性肺炎球菌病病例的峰值相关，尤其是在儿童人群中。在此，我们总结了一种受控人类感染模型的方案，旨在评估肺炎球菌和RSV联合模型中的病原体相互作用动态和免疫反应。主要目标是确定初次RSV攻击是否会增加继发性肺炎球菌定植的风险。
方法
这是一项开放标签、多中心、随机对照的人类合并感染研究，包括一个试点阶段。个体将在第0天随机接受鼻内接种肺炎球菌（6B血清型）或RSV（RSV-A亚型），然后在第7天进行交叉攻击。在试点阶段A，多达10名参与者将在RSV-A攻击后在住院设施中监测7至10天。如果没有安全问题，我们将进入门诊阶段，参与者将在家中自我隔离。从参与者采集的临床样本包括用于病原体检测的鼻拭子和冲洗液；以及用于检查黏膜和全身免疫反应的鼻细胞、鼻黏膜液和血液样本。
讨论
这项工作将产生关于肺炎球菌和RSV之间相互作用和动态的重要科学知识。这些知识有助于为肺炎球菌和RSV疫苗接种策略提供信息，特别是对于有发生严重肺炎球菌和RSV疾病风险的人群。
试验注册
该研究已在ISRCTN（英国临床研究注册中心）注册。DOI：https://doi.org/10.1186/ISRCTN12036902 。
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