Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have reported (Cubillos et al., 2008) that a synthetic dendrimeric peptide consisting of four copies of a B-cell epitope [VP1(136-154)] linked through thioether bonds to a T-cell epitope [3A(21-35)] of FMDV [B 4 T(thi)] elicits potent B- and T-cell specific responses and confers solid protection in pigs to type C FMDV challenge. Herein we show that downsized versions of this peptide bearing two copies of a B-cell epitope from a type O isolate and using thioether [B 2 T(thi)] or maleimide [B 2 T(mal)] conjugation chemistries for their synthesis elicited in swine similar or higher B and T-cell specific responses than tetravalent B 4 T(thi). Moreover, while partial protection was observed in animals immunized with B 4 T(thi) (60%) and B 2 T(thi) (80%), B 2 T(mal) conferred full (100%) protection against FMDV challenge, associated to high levels of circulating IgG2 and mucosal IgGA, and entirely prevented virus shedding. Interestingly, B 2 T(mal) is also the most advantageous option in terms of synthetic practicality. Taken together, the results reported here point out to B 2 T(mal) as a highly valuable, cost-effective FMDV candidate vaccine.