Bordetella pertussis is the causative agent of whooping cough (or pertussis) that hasbecome resurgent worldwide. Resurgence has been linked to the introduction of acellular pertussis vaccines (ACVs) and the evolution of B. pertussis away from vaccine-induced immunity. In 2012, the United Kingdom suffered a major pertussis outbreak. I conducted whole genome sequencing and genomic analysis of 95 strains including those isolated from the UK outbreak and demonstrated that although large-scale genetic changes in B. pertussis were not the cause of this outbreak, vaccine-antigen encoding genes are evolving at higher rates than other surface protein-encoding genes, this difference becoming more pronounced since the introduction of the ACV in the UK. The dramatic increase in the frequency of pertactin (Prn)-deficient strains worldwide is possibly in response to vaccine-mediated selection pressure. However, just one Prn deficient strain was identified among the UK outbreak strains. Prn expression and IgG binding to B. pertussis obtained with post-vaccine sera was determined by flow cytometry and compared between pre-outbreak and outbreak strains, but no significant differences were observed. However, a positive correlation between Prn expression and post vaccinationinduced IgG binding to strains was identified, supporting the idea that strongimmunological selection pressure is exerted on Prn and this is playing a role in theevolution of B. pertussis. The rapid evolution of vaccine-antigen encoding genes raisesserious concerns regarding the ability of current vaccines to control pertussis.
|Date of Award||29 Jun 2016|
|Supervisor||Andrew Preston (Supervisor), Andrew R Gorringe (Supervisor) & Norman K Fry (Supervisor)|