Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries

Abstract

BackgroundImmunogenicity of acellular pertussis (aP) vaccines is conventionally assessed by measuring antibody responses but antibody concentrations wane quickly after vaccination. Memory B cells, however, are critical in sustaining long-term protection and therefore may be an important factor when assessing pertussis immunity after vaccination.AimWe studied pertussis specific memory B cell (re)activation induced by an aP booster vaccination in four different age groups within three countries.Materials and methodsFrom a phase IV longitudinal interventional study, 268 participants across Finland, the Netherlands and the United Kingdom were included and received a 3-component pertussis booster vaccine: children (7-10y, n=53), adolescents (11-15y, n=66), young adults (20-34y, n=74), and older adults (60-70y, n=75). Memory B cells at baseline, day 28, and 1 year post-vaccination were measured by a pertussis toxin (Ptx), filamentous haemagglutinin (FHA), and pertactin (Prn) specific ELISpot assay. Antibody results measured previously were available for comparison. Furthermore, study participants were distributed into groups based on their baseline memory B cell frequencies, vaccine responses were monitored between these groups.ResultsGeometric mean (GM) memory B cell frequencies for pertussis antigens at baseline were low. At 28 days post-vaccination, these frequencies increased within each age group and were still elevated one year post-booster compared to baseline. Highest frequencies at day 28 were found within adolescents (GM: 5, 21, and 13, for Ptx, FHA and Prn, respectively) and lowest within older adults (GM: 2, 9, and 3, respectively). Moderate to strong correlations between memory B cell frequencies at day 28 and antibody concentrations at day 28 and 1 year were observed for Prn. Memory B cell frequencies > 1 per 100,000 PBMCs at baseline were associated with significantly higher memory responses after 28 days and 1 year.ConclusionsAn aP booster vaccine (re)activated memory B cells in all age groups. Still elevated memory B cell frequencies after one year indicates enhanced immunological memory. However, antigen specific memory B cell activation seems weaker in older adults, which might reflect immunosenescence. Furthermore, the presence of circulating memory B cells at baseline positively affects memory B cell responses. This study was registered at www.clinicaltrialsregister.eu: No. 2016-003678-42.

Booster Immunization Improves Memory B Cell Responses in Older Adults Unresponsive to Primary SARS-CoV-2 Immunization

“…A low memory B cell response to immunization has previously described in older adults for several pathogens, such as influenza and Bordetella pertussis [ 16 , 33 ]. In contrast to the current study, the majority of immunizations in older adults induce a recall response.…”

“…Generally, the age-related decline in immune function, referred to as immunosenescence, contributes to reduced vaccine efficacy in older adults, as documented for influenzavirus, for example. In addition, the antigen-specific memory B cell recall response is lower in older adults as aged memory B cells are less capable of differentiating into antibody-producing plasma cells upon boosting [ 14 , 15 , 16 ]. Responsiveness to a new antigen will be dependent on the availability and function of naïve B and T cells, which are influenced by genetics, age, and several environmental factors, among others [ 17 , 18 ].…”

Revaccination of children with acute lymphoblastic leukemia following completion of chemotherapy

“…The high percentage of children with positive serology against polio that was found in our study may be related to the oral polio vaccine that is given in Israel as part of the national immunization program and results in prolong exposure and, therefore, in better immunity. The low percentage positive serology that we found for pertussis may reflect the fact that this is the case also for healthy people with the acellular pertussis vaccine 17,18 …”

“…The low percentage positive serology that we found for pertussis may reflect the fact that this is the case also for healthy people with the acellular pertussis vaccine. 17,18 Some reports found that the younger age was significantly different in terms of losing protective antibody levels, 2 possibly related to ineffective vaccination or an incomplete national vaccination program at younger ages. 14 Toret et al 2 and Keskin Yildirim et al 19 found a negative correlation between the patient's age and losing protective antibody levels for any vaccine-preventable disease.…”

The whole-cell pertussis vaccine imposes a broad effector B cell response in mouse heterologous prime-boost settings

“…However, such a protective role provided by memory B cells was not confirmed in another mouse model of pertussis vaccination in which the authors showed poor maintenance and reactivation of the memory B cell pool ( 20 ). A more recent publication showed instead efficient memory B cell reactivation upon aP boost by comparing groups of people of different ages, from different countries, and injected with different prime vaccine types; moreover, the authors reported in this work a positive correlation between memory B cells and serum IgG concentrations ( 21 ).…”