Abstract
Pertussis, a human-specific respiratory infectious disease caused by the Gram-negative bacterium Bordetella pertussis (Bp), remains endemic with epidemic years despite high vaccination coverage. Whereas pertussis vaccines and natural infection with Bp confer immune protection, the duration of protection varies and is not lifelong. Recent evidence indicates a considerable underestimation of the pertussis burden among older adults. Whereas the impact of increasing age on Bp-specific humoral immunity has been demonstrated, little is known on immunosenescence of CD4+ T-cell responses in the context of Bp. Here, we aimed to address whether increasing age impacts responsiveness of the Bp-specific CD4+ T-cells in the memory pool following a clinically symptomatic pertussis infection in whole cell vaccine-primed pediatric and adult cases. Cytokine and proliferative responses and phenotypical profiles of CD4+ T cells specific for Bp antigens at an early and late convalescent timepoint were compared. Responses of various Th cytokines, including IFNγ, were significantly lower in older adults at early and late timepoints post diagnosis. In addition, we found lower frequencies of Bp-specific proliferated CD4+ T cells in older adults, in the absence of differences in replication profile. Phenotyping of Bp-specific CD4+ T cells suggested reduced expression of activation markers rather than increased expression of co-inhibitory markers. Altogether, our findings show that the magnitude and functionality of the Bp-specific memory CD4+ T-cell pool decrease at older age. Declined CD4+ T-cell responsiveness to Bp is suggested to contribute to the burden of pertussis in older adults.
Highlights
Pertussis is an acute and severe disease of the respiratory tract and is caused by the highly infectious and human-specific Gram-negative coccobacillus Bordetella pertussis (Bp)
To determine the impact of age on functionality of Bp-specific responses, we studied IFNγ responses in early and late phase post-infection Peripheral blood mononuclear cells (PBMCs) samples from youngsters and adult pertussis patients of the SKI cohort with a similar whole cell pertussis vaccine priming background
Production of IFNγ of 5day cultured PBMCs stimulated with protein antigens Pertussis Toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) were determined by ELISpot
Summary
Pertussis is an acute and severe disease of the respiratory tract and is caused by the highly infectious and human-specific Gram-negative coccobacillus Bordetella pertussis (Bp). Pertussis can cause serious illness in people of all ages (Hewlett and Edwards, 2005) and can even lead to fatality in newborns and young infants without protective (maternal) antibody levels (Paddock et al, 2008). It is a vaccine preventable disease, but despite high vaccine coverage, it remains endemic with outbreaks every three to 5 years (van der Maas et al, 2013; Tan et al, 2015). A large burden of disease may occur in older (vulnerable) adults and elderly, facilitating ongoing Bp transmission
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