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

Abstract

Our previous findings demonstrated that the BT 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 BT-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 BT 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 BT's ability to potentiate antigen-specific immunity through coordinated B- and T-cell activation. The study demonstrated that only BT, but not the version lacking T-cell epitope (B), triggered neutralizing antibody production and a robust T-cell response in the spleen, underscoring the critical role of CD4T-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 BT 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.