Immunogenicity of foot-and-mouth disease virus dendrimer peptides: need for a T-cell epitope and ability to elicit heterotypic responses

An approach based on a dendrimer display of B- and T-cell epitopes relevant for antibody induction has been shown to be effective as a foot-and-mouth disease (FMD) vaccine. B2T dendrimers combining two copies of the major FMD virus (FMDV) type O B-cell epitope (capsid proteinVP1 (140-158)) covalently linked to a heterotypic T-cell epitope from non-structural protein 3A (21-35), henceforth B2T-3A, has previously been shown to elicit high neutralizing antibody (nAb) titers and IFN-γ-producing cells in both mice and pigs. Here, we provide evidence that the B- and T-cell epitopes need to be tethered to a single molecular platform for successful T-cell help, leading to efficient nAb induction in mice. In addition, mice immunized with a non-covalent mixture of B2T-3A dendrimers containing the B-cell epitopes of FMDV types O and C induced similarly high nAb levels against both serotypes, opening the way for a multivalent vaccine platform against a variety of serologically different FMDVs. These findings are relevant for the design of vaccine strategies based on B- and T-cell epitope combinations. ; This research was funded by the Spanish Ministry of Science, Innovation and Universities (grants AGL2014-48923-C2 and AGL2017-84097-C2-2-R (to D.A. and F.S), and PID2019-107145RB-100 (to E.B.)), as well as by Comunidad de Madrid co-financed ECFEDER funds (S2013/ABI-350 2906-PLATESA and P2018/BAA-4370 to F.S. and E.B.), and by Generalitat de Catalunya (2009SGR492 to D.A.). Work at Centro de Biología Molecular “Severo Ochoa” and at UPF was supported by the Fundación Ramón Areces and by the Maria de Maeztu Program of the Spanish Ministry of Science, Innovation and Universities, respectively. M.F. and R.C.-A. were holders of a PhD fellowship from the Spanish Ministry of Science, Innovation and Universities.