Understanding immunity differences induced by whole cell and acellular pertussis vaccines in a paediatric population

Bordetella pertussis causes whooping cough, a life-threatening disease in infants. Both whole cell (wP) and acellular (aP) vaccines are used for infant immunisation with aP providing less robust long-term population protection. To further understand differences between wP and aP, this thesis aims: to characterise the immune response to an aP-booster in a UK cohort by age and priming backgrounds (wP/aP) using a broad variety of assays of humoral immunity; to investigate effect of HLA-DRB1-233Thr previously associated with pertussis toxin (PT) IgG antibody levels in wP-primed infants and protection from disease; to evaluate the use of continuous temperature monitoring as an objective method of evaluating reactogenicity. An aP booster gave the best responses in adolescents (aP-primed) and adults (wP-primed) in terms of antibody (highest for pertactin (Prn) and filamentous haemagglutinin (FHA) IgG), memory B-cells and novel functional assays (SBA, OPA, CDA). Prn-IgG was the antigen most closely correlated with novel functional antibody assays (SBA, OPA, CDA). For all antigens, IgA baseline and booster response increased with age, unlike IgG, suggesting a role of continued antigen exposure in generating this response. The association of HLA-DRB1-233Thr variant with PT-IgG antibody levels was replicated in wP-primed Asian infants and European adolescents. There was no indication of an additional association with any functional antibody assays assessed. However, an association with PT-IgG avidity and PT-IgA, suggested a role of this variant in enhancing immunological memory in addition to initial antibody production. Continuous temperature monitoring identified a higher number of fever episodes, characterising more accurately fever, a marker of innate immune response, post-vaccination. This thesis provides data supporting the introduction of Prn-containing aP in adolescents and adults. Investigation of the mechanisms associated to HLA-DRB1-233Thr and protection in wP-primed individuals may give further insight into differences between aP and wP vaccine responses associated with protection.