Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.690726
Title: Is the circulating UK Bordetella pertussis population evolving to evade vaccine-induced immunity?
Author: Sealey, Katie
ISNI:       0000 0004 5915 2375
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2015
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Abstract:
Bordetella pertussis is the causative agent of whooping cough (or pertussis) that has become 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 vaccination induced IgG binding to strains was identified, supporting the idea that strong immunological selection pressure is exerted on Prn and this is playing a role in the evolution of B. pertussis. The rapid evolution of vaccine-antigen encoding genes raises serious concerns regarding the ability of current vaccines to control pertussis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.690726  DOI: Not available
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