Determine the factors that influence the duration of antibody and memory B- and T-cell responses following coronavirus infection or vaccination, such as persistence of the germinal center.
Young children develop distinct immune memory characterized by different CD4+ T cell and B cell populations that are less durable, but more adaptive to variants.
Females consistently show greater antibody response and persistence than males.
Repeated antigen exposure improves antibody affinity and recognition of variants. Immune imprinting from original-strain vaccines affects responses to newer variants, limiting flexibility.
Localized in the lungs and other barrier sites. Provide rapid responses to reinfection.
Davis Porada 2024 found that vaccines that induce tissue-resident T- and B cell immunity are more protective.
Guo 2024 found that memory T cells provide more cross-reactivity to variants.
Ho 2024 found that greater numbers of antigen-specific IFNγ-secreting CD4+ T cells are associated with a stronger immune response.
Zhu 2025 found that greater numbers of antigen-specific CD8+ TRMs in the lungs are associated with better viral clearance and respiratory recovery.
Verheul 2023 found that memory B cells induced by boosters exhibit prolonged survival and a greater capacity for rapid antibody production.
He 2023 found that Tfh cells arising from natural infection offer more diverse antigen recognition due to the variety of viral epitopes encountered. Variability in cytokine secretion (e.g., IL-21, IL-4) and surface marker expression (e.g., PD-1, ICOS) between infection- and vaccination-induced Tfh cells can affect their ability to support germinal center activity and antibody affinity maturation.
The gut microbiome can influence antibody durability and T-cell differentiation. Microorganisms that produce butyrate and aromatic amino acids may be particularly beneficial.
Alexander 2023 found that lower gut microbiome diversity has been associated with diminished COVID-19 vaccine responses.
Tfh cells produce cytokines (such as IL-21) and express CD40L (aka TNFSF5) to stimulate B cell survival and differentiation. Dysregulated or dysfunctional Tfh subsets (eg TIGIT+ Tfh cells) are less capable of supporting B cell responses, leading to reduced antibody titers and impaired germinal center function.
Delayed generation of functional Tfh cells in severe COVID-19 correlates with weaker antibody responses and slower recovery.
The lack of cTfh1 activation compromises B cell support, leading to weaker humoral immunity. Patients on anti-TNF-ɑ immune suppression exhibit reduced antibody titers and impaired B cell support due to lower levels of cTfh1 cells.
Dhenni 2025 found that CD169+ subcapsular sinus macrophages interact with memory B cells in the subcapsular niche to promote GC re-entry, affinity maturation, and early bNAb generation. Prmt1 and Cr2 expression are associated with germinal center re-entry post-infection. Ipsilateral boosting is associated with more robust germinal center reactions and greater affinity maturation than contralateral boosting.
Ramirez 2024 found that older age is associated with fewer germinal center B cells.