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
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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
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
Editor(s)
Diemert, David J
Date Issued
2025-07-01
Date Acceptance
2025-04-25
Citation
PLoS One, 2025, 20 (7)
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS One
Volume
20
Issue
7
Copyright Statement
© 2025 Brito-Mutunayagam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
10.1186/ISRCTN12036902
Subjects
Humans
Streptococcus pneumoniae
Respiratory Syncytial Viruses
Respiratory Syncytial Virus, Human
Pneumococcal Infections
Respiratory Tract Infections
Respiratory Syncytial Virus Infections
Pilot Projects
Infant
Female
Male
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Coinfection
Publication Status
Published
Article Number
e0325149
Date Publish Online
2025-07-01