Abstract

For a better understanding of the maintenance of immune mechanisms to Bordetella pertussis (Bp) in relation to age, we investigated the dynamic range of specific B cell responses in various age-groups at different time points after a laboratory confirmed pertussis infection. Blood samples were obtained in a Dutch cross sectional observational study from symptomatic pertussis cases. Lymphocyte subpopulations were phenotyped by flowcytometry before and after culture. Memory B (Bmem) cells were differentiated into IgG antibody secreting cells (ASC) by polyclonal stimulation and detected by an ELISPOT assay specific for pertussis antigens pertussis toxin (Ptx), filamentous haemagglutinin (FHA) and pertactin (Prn). Bp antigen specific IgG concentrations in plasma were determined using multiplex technology. The majority of subjects having experienced a clinical pertussis episode demonstrated high levels of both Bp specific IgG and Bmem cell levels within the first 6 weeks after diagnosis. Significantly lower levels were observed thereafter. Waning of cellular and humoral immunity to maintenance levels occurred within 9 months after antigen encounter. Age was found to determine the maximum but not base-line frequencies of Bmem cell populations; higher levels of Bmem cells specific for Ptx and FHA were reached in adults and (pre-) elderly compared to under-fours and schoolchildren in the first 6 weeks after Bp exposure, whereas not in later phases. This age effect was less obvious for specific IgG levels. Nonetheless, subjects' levels of specific Bmem cells and specific IgG were weakly correlated. This is the first study to show that both age and closeness to last Bp encounter impacts the size of Bp specific Bmem cell and plasma IgG levels.

Highlights

  • Bordetella pertussis (Bp) causes the respiratory infectious disease ‘whooping cough’ which is especially hazardous for neonates

  • Age related differences in specific Bmem frequencies we studied whether age plays a role in the size range of the pertussis specific cellular compartment by comparing frequencies of pertussis toxin (Ptx), filamentous haemagglutinin (FHA), and Prn specific Bmem cells in the five age groups

  • In the present study dynamics of pertussis specific B cell responses were investigated for the first time in various age-groups comprising symptomatic pertussis patients

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Summary

Introduction

Bordetella pertussis (Bp) causes the respiratory infectious disease ‘whooping cough’ (pertussis) which is especially hazardous for neonates. The reduction of Bp circulation as a result of extensive vaccination coverage has led to less natural boostering of acquired immune mechanisms in vaccinees, leading to an increasing group of pertussis-susceptible adults. These have become a source of transmission to vulnerable groups such as elderly and infants too young to be (fully) vaccinated. The aim of the present study was to gain insight into the dynamic range of pertussis specific IgG and Bmem cell responses induced by symptomatic pertussis infection in various age-groups. Patterns observed in the Bmem cell compartment were analysed in relation to humoral responses

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