title: Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis.
abstract: Capturing the complexity and waning patterns of co-occurring immunoglobulin (Ig) responses after clinical B. pertussis infection may help understand how the human host gradually loses protection against whooping cough. We applied bi-exponential modelling to characterise and compare B. pertussis specific serological dynamics in a comprehensive database of IgG, IgG subclass and IgA responses to Ptx, FHA, Prn, Fim2/3 and OMV antigens of (ex-) symptomatic pertussis cases across all age groups. The decay model revealed that antigen type and age group were major factors determining differences in levels and kinetics of Ig (sub) classes. IgG-Ptx waned fastest in all age groups, while IgA to Ptx, FHA, Prn and Fim2/3 decreased fast in the younger but remained high in older (ex-) cases, indicating an age-effect. While IgG1 was the main IgG subclass in response to most antigens, IgG2 and IgG3 dominated the anti-OMV response. Moreover, vaccination history plays an important role in post-infection Ig responses, demonstrated by low responsiveness to Fim2/3 in unvaccinated elderly and by elevated IgG4 responses to multiple antigens only in children primed with acellular pertussis vaccine (aP). This work highlights the complexity of the immune response to this re-emerging pathogen and factors determining its Ig quantity and quality.
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: Inonge
authors.initials: I
authors.lastname: van Twillert
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: Axel A
authors.initials: AA
authors.lastname: Bonačić Marinović
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: Betsy
authors.initials: B
authors.lastname: Kuipers
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: Jacqueline A M
authors.initials: JA
authors.lastname: van Gaans-van den Brink
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.|Department of Immunology and Infectious Diseases, Wilhelmina Childrens Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: Cécile A C M
authors.initials: CA
authors.lastname: van Els
mesh_terms: D000367:Age Factors; D000942:Antigens, Bacterial / Q000276:immunology; D001886:Bordetella pertussis / Q000472:pathogenicity*; D002648:Child; D045142:Cross-Priming / Q000276:immunology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D013223:Statistics as Topic; D013997:Time Factors; D014611:Vaccination; D014917:Whooping Cough / Q000097:blood* / Q000276:immunology* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D007136:Immunoglobulins