Abstract
Synthetic dendrimer peptides are a promising strategy to develop new FMD vaccines. A dendrimer peptide, termed B2T-3A, which harbors two copies of the major FMDV antigenic B-cell site [VP1 (140–158)], covalently linked to a heterotypic T-cell from the non-structural protein 3A [3A (21–35)], has been shown to protect pigs against viral challenge. Interestingly, the modular design of this dendrimer peptide allows modifications aimed at improving its immunogenicity, such as the replacement of the T-cell epitope moiety. Here, we report that a dendrimer peptide, B2T-3D, harboring a T-cell epitope from FMDV 3D protein [3D (56–70)], when inoculated in pigs, elicited consistent levels of neutralizing antibodies and high frequencies of IFN-γ-producing cells upon in vitro recall with the homologous dendrimers, both responses being similar to those evoked by B2T-3A. Lymphocytes from B2T-3A-immunized pigs were in vitro-stimulated by T-3A peptide and to a lesser extent by B-peptide, while those from B2T-3D- immunized animals preferentially recognized the T-3D peptide, suggesting that this epitope is a potent inducer of IFN-γ producing-cells. These results extend the repertoire of T-cell epitopes efficiently recognized by swine lymphocytes and open the possibility of using T-3D to enhance the immunogenicity and the protection conferred by B2T-dendrimers.
Highlights
Foot-and-mouth disease (FMD) is a highly contagious disease affecting cloven-hoofed animals that is caused by a virus belonging to the Picornaviridae family: FMD virus (FMDV)
We show that a B2T-dendrimer including the porcine T-cell epitope identified in the 3D FMDV protein [3D [56–70]] previously shown to be promiscuous and heterotypic T-cell epitope [24] can elicit in pigs neutralizing antibodies (nAbs) titers and IFN-γ-producing cells at levels similar to those induced by the dendrimer peptide B2T-3A
Analysis of the Humoral Immune Response Elicited by B2T-3D FMDV Dendrimer in a Mouse Model
Summary
Foot-and-mouth disease (FMD) is a highly contagious disease affecting cloven-hoofed animals that is caused by a virus belonging to the Picornaviridae family: FMD virus (FMDV). The mortality rate is low, FMD is feared in farm industry and animal health because, in an outbreak, massive culling of infected or suspected animals is mandatory, with devastating economic impact. FMD control is costly in endemic countries in which current vaccines based on inactivated viruses are being used for disease control [1]. Several drawbacks associated with these vaccines have led FMD-free countries to follow non-vaccination policies, increasing the risk of disease reintroduction and severe outbreaks [2]. The development of safer and effective vaccines is a major priority for FMD control including those based on viral subunits [3,4,5].
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