B epitope multiplicity and B/T epitope orientation influence immunogenicity of foot-and-mouth disease peptide vaccines

Synthetic peptides incorporating protective B- and T-cell epitopes are candidates for new safer foot-and-mouth disease (FMD) vaccines. We have reported that dendrimeric peptides including four copies of a B-cell epitope (VP1 136 to 154) linked to a T-cell epitope (3A 21 to 35) of FMD virus (FMDV) elicit potent B- and T-cell specific responses and confer protection to viral challenge, while juxtaposition of these epitopes in a linear peptide induces less efficient responses. To assess the relevance of B-cell epitope multivalency, dendrimers bearing two (B2T) or four (B4T) copies of the B-cell epitope from type O FMDV (a widespread circulating serotype) were tested in CD1 mice and showed that multivalency is advantageous over simple B-T-epitope juxtaposition, resulting in efficient induction of neutralizing antibodies and optimal release of IFN γ . Interestingly, the bivalent B2T construction elicited similar or even better B- and T-cell specific responses than tetravalent B4T. In addition, the presence of the T-cell epitope and its orientation were shown to be critical for the immunogenicity of the linear juxtaposed monovalent peptides analyzed in parallel. Taken together, our results provide useful insights for a more accurate design of FMD subunit vaccines.Research at CBMSO was funded by Spanish MINECO (BIO2011-24351), and by an institutional grant from Fundación Ramón Areces. Research at Universitat Pompeu Fabra was funded by the Spanish MINECO (SAF2011-24899) and by Generalitat de Catalunya (SGR2009-00492). Research at INIA was funded by the European Community’s Seventh Framework Programme (FP7, 2007-2013), Research Infrastructures action, under the grant agreement no. FP7-228394 (NADIR) and Spanish MINECO (AGL2010-22200-C02-02 and CC07-062). Noelia Moreno is a predoctoral (FPI) fellow from the Spanish MEC