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.
<h4>Background</h4>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 syne...
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2025-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0325149 |
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| author | Sanjita Brito-Mutunayagam David O Hamilton Elena Mitsi Carla Solórzano Grace Li Bruno Rocha De Macedo Filora Elterish Xinxue Liu Kiarash Tanha Rachel White Angela Hyder-Wright Bhumika Patel Britta C Urban Conor Whelan Hanane Trari Belhadef Hannah Robinson Emma Plested Amber Thompson Maria Lahuerta Isis Kanevsky Kena Swanson Negar Aliabadi Julie Catusse Christian Theilacker Bradford D Gessner Natalie I Mazur Christopher Chiu Andrea M Collins Ben Morton Maheshi N Ramasamy Daniela M Ferreira |
| author_facet | Sanjita Brito-Mutunayagam David O Hamilton Elena Mitsi Carla Solórzano Grace Li Bruno Rocha De Macedo Filora Elterish Xinxue Liu Kiarash Tanha Rachel White Angela Hyder-Wright Bhumika Patel Britta C Urban Conor Whelan Hanane Trari Belhadef Hannah Robinson Emma Plested Amber Thompson Maria Lahuerta Isis Kanevsky Kena Swanson Negar Aliabadi Julie Catusse Christian Theilacker Bradford D Gessner Natalie I Mazur Christopher Chiu Andrea M Collins Ben Morton Maheshi N Ramasamy Daniela M Ferreira |
| author_sort | Sanjita Brito-Mutunayagam |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.<h4>Trial registration</h4>The study is registered on ISRCTN (The UKs Clinical Study Registry). DOI https://doi.org/10.1186/ISRCTN12036902. |
| format | Article |
| id | doaj-art-56a13d508b9f4c29ab60d16cf1576e06 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-56a13d508b9f4c29ab60d16cf1576e062025-08-20T02:36:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01207e032514910.1371/journal.pone.0325149Understanding 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.Sanjita Brito-MutunayagamDavid O HamiltonElena MitsiCarla SolórzanoGrace LiBruno Rocha De MacedoFilora ElterishXinxue LiuKiarash TanhaRachel WhiteAngela Hyder-WrightBhumika PatelBritta C UrbanConor WhelanHanane Trari BelhadefHannah RobinsonEmma PlestedAmber ThompsonMaria LahuertaIsis KanevskyKena SwansonNegar AliabadiJulie CatusseChristian TheilackerBradford D GessnerNatalie I MazurChristopher ChiuAndrea M CollinsBen MortonMaheshi N RamasamyDaniela M Ferreira<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.<h4>Trial registration</h4>The study is registered on ISRCTN (The UKs Clinical Study Registry). DOI https://doi.org/10.1186/ISRCTN12036902.https://doi.org/10.1371/journal.pone.0325149 |
| spellingShingle | Sanjita Brito-Mutunayagam David O Hamilton Elena Mitsi Carla Solórzano Grace Li Bruno Rocha De Macedo Filora Elterish Xinxue Liu Kiarash Tanha Rachel White Angela Hyder-Wright Bhumika Patel Britta C Urban Conor Whelan Hanane Trari Belhadef Hannah Robinson Emma Plested Amber Thompson Maria Lahuerta Isis Kanevsky Kena Swanson Negar Aliabadi Julie Catusse Christian Theilacker Bradford D Gessner Natalie I Mazur Christopher Chiu Andrea M Collins Ben Morton Maheshi N Ramasamy Daniela M Ferreira 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. PLoS ONE |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| url | https://doi.org/10.1371/journal.pone.0325149 |
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