Dr Khandaker Shadia MBBS, MPhil, PhD

Streptococcus pneumoniae (the pneumococcus) and Respiratory Syncytial Virus (RSV) are two major pathogens commonly found to coexist in respiratory secretions in patients with acute upper respiratory tract infections. Though there is increasing evidence of a synergistic interplay between these pathobionts, the exact mechanisms remain obscure. To date, most RSV-pneumococci coinfection models aimed to study the secondary pneumococcal infection after a primary RSV exposure, even though the most likely scenario is that pneumococcal colonisation occurs at a younger age prior to any exposure to viral pathogens. Therefore, my project adopted an infection protocol where S. pneumoniae pre-exposed mice are superinfected with RSV to understand how the virus facilitates pneumococcal carriage and invasive disease. Along with the animal model, this project exploits in vitro respiratory epithelial cell culture model and global proteomic analysis approach to understand the coinfection dynamics.

Research in the past decade has convincingly shown that the bacterial communities found in the nasopharynx have an important contributory effect on upper respiratory tract infections (URTIs). However, it remains unclear how exactly the nasopharyngeal bacterial microbiota might influence the course of viral illnesses, and vice versa. This project brings the focus on Respiratory syncytial virus (RSV) and Human Rhinovirus (HRV) – the two most common global causes of acute respiratory tract infections (ARIs) in paediatric patients. This project involves the analysis of nasopharyngeal aspirates samples collected from infants younger than 6 months of age. High-throughput species-level metagenomic sequencing of these samples will allow us to identify differences in bacterial population diversity at the species level. Additionally, comprehensive immune profiling using highly sensitive multiplex immunoassays will guide us to find specific immune biomarkers.

Group B Streptococcus (GBS) is one of the global leading causes of neonatal and infant mortality, which is more serious in some low- and middle-income countries (LMICs). Interestingly, LMICs situated in South-East Asia report a low GBS disease burden while high GBS disease rates are documented on the African continent and in Europe. Amongst several possible causes, one may be the differences in immune protection. This project aims to understand the immune-mediated heterogeneity, if there is any, in the context of high- vs low- GBS prevalence countries. The project encompasses the analysis of physicochemical and functional properties of anti-GBS IgG antibodies by using Luminex platform, surface plasmon resonance (Biacore), glycosylation profiling and opsonophagocytic killing assay. Placental transfer and protective efficacy are assessed in a novel humanised mouse model. Altogether this project will significantly help towards the design of more efficient vaccines and to find the correlates of protection to fight against life-threatening GBS disease.