Induction and maintenance of Bordetella pertussis specific immune responses

Abstract

Pertussis, also referred to as whooping cough, is a serious respiratory disease mainly caused by the gram-negative bacterium Bordetella pertussis. The disease is most severe in neonates and children under the age of 1. Before childhood vaccination was introduced in the 1950s, pertussis was an important cause of infant death throughout the world. Worldwide introduction of vaccination of children significantly reduced the number of pertussis cases but B. pertussis has remained endemic. Moreover, in countries with well-implemented infant vaccination programmes, including the Netherlands, a remarkable resurgence of pertussis has been observed in the last decades, leading to renewed interest in pertussis vaccine efficacy. In addition to changes in transmission patterns, the emergence of new variants of B. pertussis and improved diagnosis/reporting, waning immunity has been proposed as a major factor for the increasing incidence of whooping cough. In this thesis, we described studies with the principal aim to characterise key features, strengths and weaknesses, of early and late immune responses following B. pertussis infection or vaccination. In summary, using various techniques and different host models, we focussed on early innate events of immune responses and on the longevity and flavour of the adaptive immunity. We showed that both innate and adaptive immune responses are important for protection against pertussis and that vaccine induced immunological memory is not life-long. Several peculiarities in murine and human pertussis specific cellular responses were observed that shed new light on the flaws rather than the strengths of immunity to pertussis. Ultimately, by putting our findings in a wider context of immunological models, we propose measures how to adapt pertussis vaccines or vaccination practice such that one or more of three different phases of adaptive immune responses are modulated, resulting in higher maintenance levels of immunological protection needed to resist current B. pertussis strains