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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Understanding the interaction of upper respiratory tract infection with respiratory syncytial virus and Streptococcus
Sanjita Brito-Mutunayagam1, David O Hamilton2, Elena Mitsi1,2
1Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
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.
Insights
This study investigates how respiratory syncytial virus (RSV) affects the risk of secondary Streptococcus pneumoniae (pneumococcus) infection. Understanding these interactions can improve vaccination strategies for respiratory infections.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Streptococcus pneumoniae (pneumococcus) and respiratory syncytial virus (RSV) are leading global causes of respiratory infections.
- Co-infections with these pathogens can synergistically increase disease severity and evade host immune responses.
- RSV outbreaks are linked to increased invasive pneumococcal disease, especially in children.
Purpose of the Study:
- To evaluate pathogen interaction dynamics and immune responses in a controlled human co-infection model of pneumococcus and RSV.
- To determine if primary RSV challenge increases the risk of secondary pneumococcal colonization.
Main Methods:
- An open-label, multi-center, randomized controlled human co-infection study with a pilot phase.
- Participants receive intra-nasal inoculation with either pneumococcus (serotype 6B) or RSV (subtype RSV-A) on day 0, followed by reciprocal challenge on day 7.
- Collection of nasal swabs/washes for pathogen detection and samples (nasal cells, lining fluid, blood) for immune response analysis.
Main Results:
- Pilot phase A involves in-patient monitoring of up to 10 participants for 7-10 days post-RSV-A challenge.
- Progression to an outpatient phase with self-isolation is contingent on safety findings from the pilot phase.
- Detailed analysis of pathogen dynamics and host immune responses will be conducted.
Conclusions:
- This research will generate critical knowledge on pneumococcus and RSV interactions.
- Findings may inform improved vaccination strategies for both pneumococcal and RSV diseases.
- Particular focus on at-risk populations susceptible to severe co-infection outcomes.
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