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

Abstract

The generation of a specific long-term immune response to SARS-CoV-2 is considered important for protection against COVID-19 infection and disease. Memory B cells, responsible for the generation of antibody-producing plasmablasts upon a new antigen encounter, play an important role in this process. Therefore, the induction of memory B cell responses after primary and booster SARS-CoV-2 immunizations was investigated in the general population with an emphasis on older adults. Participants, 20–99 years of age, due to receive the mRNA-1273 or BNT162b2 SARS-CoV-2 vaccine were included in the current study. Specific memory B cells were determined by ex vivo ELISpot assays. In a subset of participants, antibody levels, avidity, and virus neutralization capacity were compared to memory B cell responses. Memory B cells specific for both Spike S1 and receptor-binding domain (RBD) were detected in the majority of participants following the primary immunization series. However, a proportion of predominantly older adults showed low frequencies of specific memory B cells. Booster vaccination resulted in a large increase in the frequencies of S1- and RBD-specific memory B cells also for those in which low memory B cell frequencies were detected after the primary series. These data show that booster immunization is important for the generation of a memory B cell response, as a subset of older adults shows a suboptimal response to the primary SARS-CoV-2 immunization series. It is anticipated that these memory B cells will play a significant role in the immune response following viral re-exposure.

Contribution of SARS-CoV-2 infection preceding COVID-19 mRNA vaccination to generation of cellular and humoral immune responses in children

“…Part of the antibody data measured for 12–17-year-old participants has previously been published in a study showing that the antibody levels in younger individuals are generally higher, compared to those in (older) adults ( 12 ). Interestingly, the numbers of memory B cells in children are lower compared to those we previously determined in adults (18-50 years of age) after two vaccine doses without a previous infection ( 18 ) (median = 1.25/1*10 5 PBMC for children (n = 7) and 10.5/1*10 5 PBMC for adults (n = 32). This potentially indicates that B cells in children are more likely to become antibody-producing plasmablasts after COVID-19 mRNA vaccination, while B cells in adults may be more likely to differentiate into memory B cells.…”

“…Once received by the laboratory at the National Institute for Public Health and the Environment (RIVM), the Netherlands, serum from microtubes and from blood sample tubes were spun down and frozen at -80°C as previously described ( 12 ). Heparin tubes were used to collect PBMCs (subgroup only), which were isolated with Lymphoprep as described previously ( 18 ).…”

“…SARS-CoV-2 B cell ELISpots were carried out as described previously ( 18 ). In short, PBMC samples were cultured for 5 days in AIM-V medium with 10% heat-inactivated FBS, 50uM β mercaptoethanol, 3µg/ml CpG, 10ng/ml recombinant Interleukin 2 and 10ng/ml recombinant interleukin 10.…”

Risk of severe COVID-19 in unvaccinated patients during the period from wild-type to Omicron variant: real-world evidence from Japan

“…A large national cohort study [ 20 ] assessed age-specific estimates of the risk of severe outcomes for Omicron relative to Delta, and reported that the adjusted hazard ratio of death was approximately three times higher for unvaccinated patients aged at least 80 years compared with those aged 30–39. A recent study [ 21 ] reported that older people tended to have lower frequencies of specific memory B cell responses after the primary vaccination series than younger people, but that the booster vaccination produced a great increase in the frequencies of memory B cells for older people with low frequencies after the primary series. These previous studies [ 19 – 21 ] support our findings that among older people aged 80 and older, it is more difficult to reduce the risk of severe COVID-19, but that booster vaccination is more effective, compared to younger people.…”

“…A recent study [ 21 ] reported that older people tended to have lower frequencies of specific memory B cell responses after the primary vaccination series than younger people, but that the booster vaccination produced a great increase in the frequencies of memory B cells for older people with low frequencies after the primary series. These previous studies [ 19 – 21 ] support our findings that among older people aged 80 and older, it is more difficult to reduce the risk of severe COVID-19, but that booster vaccination is more effective, compared to younger people.…”