| Project Detail |
Pneumonia is the number one infectious cause of death in children worldwide. Many of the viruses and bacteria that cause pneumonia regularly infect, or colonize, the upper respiratory tract (URT) without causing disease. This drives community transmission but is also an important source of immunity. The processes and key host immune and microbiota factors that determine the infection kinetics, transmission and development of immunity during such infections need elucidation.
I have recently optimized minimally-invasive nasal sampling analysis methods using Synthetic Absorptive Matrix (SAM) strips that now allow me to address these knowledge gaps. Through the daily collection of such well-tolerated nasal samples in children, I will study non-pathological, naturally-acquired URT infections, but also controlled infections in an ethical and safe manner using the live attenuated influenza vaccine. In addition, I will perform high frequency nasal sampling in groups of schoolchildren to precisely measure transmission events over time and even infer exposure. Incoming bacteria, viruses and the resident URT microbiome as well as mucosal host innate and adaptive immune responses will be quantified in parallel throughout infections using existing and new high-throughput assays, including an antigen array and microfluidic qPCR for 32 pathogens. Multi-omics integrative time-series analyses and mathematical modelling will be used to identify parameters that are central and predictive for pathogen acquisition, replication and clearance; as well as for transmission and immune boosting. Key novel markers and concepts will be validated using state-of-the-art in vitro mucosal models.
The comprehensive and detailed understanding of URT infections obtained in this project can lead to better diagnostics, mucosal targeted therapies and vaccines, and provide a basis for the improved predictions of pathogen spread and public health effects of interventions at the population level. |
