Long-Term Effectiveness of BNT162b2 Pfizer-BioNTech mRNA-Based Vaccine on B Cell Compartment: Efficient Recall of SARS-CoV-2-Specific Memory B Cells.

At present, there is a lack of clinical evidence about the impact and long-term durability of the immune response induced by the third dose of mRNA vaccines. In this study, we followed up the B cell compartment behavior in a cohort of immunocompetent individuals three and six months after the third dose of vaccine. During this period, some subjects contracted the virus. In uninfected vaccinated subjects, we did not report any changes in serum spike-specific IgG levels, with a significant reduction in IgA. Instead, subjects recovered from natural infection showed a significant increase in both specific IgG and IgA. Moreover, we showed a time-related decrease in IgG neutralizing potential to all SARS-CoV-2 variants of concern (VOC) in uninfected compared to recovered subjects, who displayed an increased neutralizing ability, particularly against the omicron variant. Finally, we underlined the presence of a pool of SARS-CoV-2-specific B cells in both groups that are prone to respond to restimulation, as demonstrated by their ability to differentiate into plasma cells and to produce anti-SARS-CoV-2-specific immunoglobulins. These data lead us to assert the long-term effectiveness of the BNT162b2 vaccine in contrasting the severe form of the pathology and prevent COVID-19-associated hospitalization.

Young but not older adults exhibit an expansion of CD45RA+CCR7+CD95+ T follicular helper cells in response to tetanus vaccine.

A subset of CD4+ T cells, known as T follicular helper (Tfh), provides co-stimulating signals required to establish long-term humoral immunity. Recent studies have shown a reduced frequency and functionality of this population in older adults in comparison to young adults, in response to vaccination. To evaluate whether memory generation of circulating Tfh (cTfh) cells contributes to this phenomenon, the memory subpopulations of cTfh, and their activation degree, were evaluated both ex-vivo and in-vitro, in response to the model antigen tetanus toxoid (TT) after the first dose of tetanus vaccine. Here, we report a lower frequency of cTfh after vaccination in older adults compared to young adults. Moreover, whereas cTfh from older adults preferably expanded with an effector memory phenotype, young adults experienced a temporal increase of CCR7+CD45RA+ cTfh cells, which also displayed higher levels of CD95, CD40L, CXCR3, and Bcl-6 upon antigen re-encounter. This phenotype was confirmed using automatized algorithm. In conclusion, our results suggest that an age-related loss of heterogeneity and an expansion of more differentiated memory cells within the cTfh compartment could affect the responsiveness of older individuals to vaccines, making this phenotype a characteristic feature of immunosenescence.