Inclusion of a specific T cell epitope increases the protection conferred against foot-and-mouth disease virus in pigs by a linear peptide containing an immunodominant B cell site

Background: Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals. FMD control in endemic regions is implemented using chemically inactivated whole-virus vaccines. Currently, efforts are directed to the development of safe and marked vaccines. We have previously reported solid protection against FMDV conferred by branched structures (dendrimeric peptides) harbouring virus-specific B and T-cell epitopes. In order to gain insights into the factors determining a protective immune response against FMDV, in this report we sought to dissect the immunogenicity conferred by different peptide-based immunogens. Thus, we have assessed the immune response and protection elicited in pigs by linear peptides harbouring the same FMDV B-cell or B and T-cell epitopes (B and TB peptides, respectively). Results: Pigs were twice immunized with either the B-cell epitope (site A) peptide or with TB, a peptide where the B-cell epitope was in tandem with the T-cell epitope [3A (21-35)]. Both, B and TB peptides were able to induce specific humoral (including neutralizing antibodies) and cellular immune responses against FMDV, but did not afford full protection in pigs. The data obtained showed that the T-cell epitope used is capable to induce efficient T-cell priming that contributes to improve the protection against FMDV. However, the IgA titres and IFNγ release elicited by these linear peptides were lower than those detected previously with the dendrimeric peptides. Conclusions: We conclude that the incorporation of a FMDV specific T-cell epitope in the peptide formulation allows a significant reduction in virus excretion and clinical score after challenge. However, the linear TB peptide did not afford full protection in challenged pigs, as that previously reported using the dendrimeric construction indicating that, besides the inclusion of an adecuate T-cell epitope in the formulation, an efficient presentation of the B-cell epitope is crucial to elicit full protection by peptide vaccines.Work at CBMSO and INIA was supported by Spanish grants from CICYT (BIO2008-0447-C03-01 and AGL2010-22200-C02-02), MEC (PORCIVIR, CSD2006-0007), Fundación Ramón Areces and by EU Network of Excellence, EPIZONE (ContractNoFOODCT-2006-016236). Work at UPF was supported by the Spanish Ministry of Education and Science (grant BIO2002-04091-C03-01 and BIO2005-07592-CO2-02) and by Generalitat de Catalunya (SGR00494 and CIDEM-BAPP