Foot-and-mouth disease virus-derived dendrimer peptides induce germinal center-dependent antibody responses and IgG1 plasma cell differentiation in mice

Our previous findings demonstrated that the B₂T dendrimer peptide, harboring B- and T-cell foot-and-mouth disease virus (FMDV) epitopes, confers protection in swine and elicits in mice significant levels of neutralizing antibodies, a key correlate of protection against FMDV. Here, we use a mouse model to study the germinal center (GC) B-cell response in B₂T-immunized mice, as this peptide is aimed to enhance antigen-specific immune responses, relying on T-cell help to potentiate B-cell activation and maturation. Flow cytometry revealed that immunization with B₂T enhanced GC formation and increased the proportion of IgG1-positive GC B-cells in draining lymph nodes. Additionally, elevated levels of IgG1-secreting B-cells in bone marrow are consistent with the initiation of GC-derived plasma cell differentiation, highlighting B₂T's ability to potentiate antigen-specific immunity through coordinated B- and T-cell activation. The study demonstrated that only B₂T, but not the version lacking T-cell epitope (B₂), triggered neutralizing antibody production and a robust T-cell response in the spleen, underscoring the critical role of CD4⁺ T-cell help mediated by the T-cell epitope in eliciting protective immunity. Even though these studies need to be extended to natural hosts such as swine, our results highlight the role of the B₂T dendrimer in inducing IgG1-secreting long-lived plasma cells in the bone marrow, providing insights into the mechanisms underlying the durable immunity elicited by epitope-linked dendrimer vaccines.