Biology subjects

Wijburg, O.

Publications and source records attributed to Wijburg, O..

3 recordsLinked to original sources

bioRxiv2025

Nasopharyngeal colonisation by Streptococcus pneumoniae enhances host anti-viral responses to respiratory virus infection

Viral-bacterial interactions during co-infection are often synergistic and can increase disease severity. However, emerging evidence indicates that some bacteria can antagonise viral infection, although the host responses driving this process remains unclear. Using infant mice co-infected with the nasopharyngeal inhabitant and pathogen Streptococcus pneumoniae and pneumonia virus of mice (PVM) to model antagonistic interactions, we found that prior bacterial colonisation enhances and prolongs anti-viral immune responses during co-infection, compared with viral infection alone. Transcriptomic, immunological, and histological analyses showed that pneumococcal colonisation prior to PVM infection enhanced and prolonged interferon signalling, increased anti-viral cytokine and chemokine protein levels and CD8+ cell responses. Notably, over 50% of differentially expressed host genes during co-infection were not differentially expressed in either infection alone. Our work shows that bacterial colonisation can modulate host immunity, shaping how the immune system responds to incoming viral infections, which has the potential to open novel therapeutic applications. HighlightsO_LIPneumococcal mono-infection in infant mice resulted in a delayed host transcriptomic response that was not detectable until 12 days post-infection. C_LIO_LIHost transcriptomic and immune responses to PVM were minimal except at the peak of viral replication and rapidly returned to baseline levels. C_LIO_LIPrior pneumococcal colonisation enhanced anti-viral immune responses to PVM infection, with more than half of the differentially expressed genes unique to co-infection. C_LIO_LIPneumococcal nasopharyngeal colonisation shapes the immune response, changing how the host responds to incoming viral infections with multiple anti-viral responses that were only transiently activated during PVM mono-infection being active for a longer duration during co-infection C_LI

microbiology↗

bioRxiv2023

Therapeutic immunization with a whole cell vaccine reduces pneumococcal nasopharyngeal density, shedding, and middle ear infection in mice

Pneumococcal Conjugate Vaccines (PCVs) have substantially reduced the burden of disease caused by Streptococcus pneumoniae (the pneumococcus). However, protection is limited to vaccine serotypes, and when administered to children who are colonized with pneumococci at the time of vaccination, immune responses to the vaccine are blunted. Here, we investigate the potential of a killed whole cell pneumococcal vaccine (WCV) to reduce existing pneumococcal carriage and mucosal disease when given therapeutically to infant mice colonized with pneumococci. We show that a single dose of WCV reduced pneumococcal carriage density in an antibody-dependent manner. Therapeutic vaccination induced robust immune responses to pneumococcal surface antigens CbpA, PspA (family 1) and PiaA. In a co-infection model of otitis media, a single dose of WCV reduced pneumococcal middle ear infection. Lastly, in a two-dose model, therapeutic administration of WCV reduced nasal shedding of pneumococci. Taken together, our data demonstrate that WCV administered in colonized mice reduced pneumococcal density in the nasopharynx and the middle ear, and decreased shedding. A vaccine with similar properties in children would be beneficial in low and middle-income settings where pneumococcal carriage is high. ImportanceAlthough typically asymptomatic, pneumococcal carriage plays an essential role in transmission and the development of disease. Pneumococcal Conjugate Vaccines (PCVs) have reduced the burden of pneumococcal disease worldwide. However, their use has increased carriage and disease caused by non-vaccine serotypes, prompting investigations into serotype-independent pneumococcal vaccines. An additional limitation of PCVs is immune hypo-responsiveness to vaccines in children carrying pneumococci at the time of vaccination. Therefore, there is great interest in next generation vaccines such as whole cell vaccines. In this study we investigate a pneumococcal whole cell vaccine (WCV) for it effect on carriage in mice that are already colonized at the time of vaccination. We show that this therapeutic vaccination of mice can reduce pneumococcal carriage density, shedding and infection of the middle ear. Our study suggests that WCV could be beneficial in high burden settings where carriage at the time of vaccination is more common.

microbiology↗

bioRxiv2020

Synergism and antagonism of bacterial-viral co-infection in the upper respiratory tract

Streptococcus pneumoniae (the pneumococcus) is a leading cause of pneumonia in children under five years old. Co-infection by pneumococci and respiratory viruses enhances disease severity. Little is known about pneumococcal co-infections with Respiratory Syncytial Virus (RSV). Here, we developed a novel infant mouse model of co-infection using Pneumonia Virus of Mice (PVM), a murine analogue of RSV, to examine the dynamics of co-infection in the upper respiratory tract, an anatomical niche that is essential for host-to-host transmission and progression to disease. Coinfection increased damage to the nasal tissue and increased production of the chemokine CCL3. Pneumococcal nasopharyngeal density and shedding in nasal secretions were increased by co-infection. In contrast, co-infection reduced PVM loads in the nasopharynx, an effect that was independent of pneumococcal strain and the order of infection. We showed this antagonistic effect was abrogated using a pneumococcal mutant deficient in capsule production and incapable of nasopharyngeal carriage. The pneumococcal-mediated reduction in PVM loads was caused by accelerated viral clearance from the nasopharynx. Although these synergistic and antagonistic effects occurred with both wild-type pneumococcal strains used in this study, the magnitude of the effects was strain dependent. Lastly, we showed that pneumococci can also antagonize influenza virus. Taken together, our study has uncovered multiple novel facets of bacterial-viral co-infection. Our findings have important public health implications, including for bacterial and viral vaccination strategies in young children.

microbiology↗