Abstract
The success of most vaccines relies on the generation of antibodies to provide protection against subsequent infection; this in turn depends on a robust germinal centre (GC) response that culminates in the production of long-lived antibody-secreting plasma cells. The size and quality of the GC response are directed by a specialised subset of CD4 + T cells: T follicular helper (Tfh) cells. Tfh cells provide growth and differentiation signals to GC B cells and mediate positive selection of high-affinity B cell clones in the GC, thereby determining which B cells exit the GC as plasma cells and memory B cells. Because of their central role in the production of long-lasting humoral immunity, Tfh cells represent an interesting target for rational vaccine design.
Highlights
Vaccination is one of the most successful, cost-effective interventions for combating infectious disease, thereby reducing infectionrelated disease, disability and death worldwide[1]
Concluding remarks The germinal centre (GC) is critical for the production of long-lived antibodysecreting plasma cells after vaccination, making it a promising cellular response to improve vaccine efficacy
There are many players in the GC response; T follicular helper (Tfh) and T follicular regulatory (Tfr) cells tightly control its size and output and make them key targets to manipulate in vaccine design
Summary
Vaccination is one of the most successful, cost-effective interventions for combating infectious disease, thereby reducing infectionrelated disease, disability and death worldwide[1]. TLR signalling in DCs and B cells could be directed to enhance vaccine antibody and Tfh cell responses Another potential strategy to enhance Tfh cell numbers is to use adjuvants to modulate the cytokines produced by antigen-presenting cells to promote Tfh cell differentiation. CTLA-4 is a suppressive mechanism by which Treg and Tfr cells can control GC response to vaccination through limiting CD28 signalling that is important for Tfh maintenance[17,113,114] Inhibiting this receptor in mice increases the number of antigen-specific Tfh cells, plasma and memory B cells following immunisation. Recent research into next-generation adjuvants demonstrates that adjuvants that support enhanced antibody production associate with increased numbers of Tfh cell in experimental animals To determine whether this can translate into enhanced Tfh responses in humans, cTfh cells will be a useful biomarker of GC Tfh responses in preliminary clinical trials.
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