Improving pertussis vaccines: a proteomics-based approach to identify novel vaccine candidates

Pertussis is a serious respiratory disease caused by Bordetella pertussis. Before childhood vaccination was introduced in the 1950s, it was a major cause of infant death throughout the world. Widespread vaccination of children has resulted in significantly reduced morbidity and mortality. However, in the 1990s a resurgence of pertussis was observed in many countries with highly vaccinated populations and pertussis has become the most prevalent vaccine-preventable disease in developed countries. In the Netherlands, the estimated incidence of infection was 6.6% per year for 3-79 year olds in 1995-1996. Similar percentages have been found in the USA. One of the hallmarks of the resurgence of pertussis is, that the largest increase in disease incidence is found in adolescents and adults. Contrary to common perceptions, complications of pertussis, including serious ones, are not uncommon in adolescents and adults. There is consensus that the resurgence of pertussis is mainly caused by the inability of current vaccines to induce long-lasting immunity. Further, antigenic divergence between vaccine strains and clinical isolates may have aggravated the effect of waning immunity. Current bacterial vaccines are based on planktonic cells while it has become apparent recently that conditions in biofilms are more representative of those during natural infection. Further, pertussis vaccines are derived from strains isolated in the 1950s, which have been shown to differ significantly from current strains. In this project, novel protein vaccine candidates will be identified using modern strains and a mass spectrometry-based approach. The focus will be on conserved, surface-exposed, proteins, which are expressed in biofilms and during infection. The ability of these proteins to confer long-term protection will be compared to antigens currently used in pertussis vaccines in experimental models. Trefwoorden: Bacterial_vaccines, pertussis, whooping_cough, proteomics, infectious_diseases,