Short Running title: FMDV VLPs and ISPA enhance protection against FMD
Keywords: FMDV1, Virus-Like Particles2, protection3, ISPA4, vaccine5, adjuvant6,
Abstract
Foot and Mouth Disease Virus (FMDV) causes an acute disease with important economy losses worldwide. Currently available vaccines are based on inactivated FMDV and oil-adjuvants. The use of Virus-Like Particles (VLPs) for subunit vaccines has been reported to be promising since it avoids the biological hazard of using virus in vaccine production while conserving conformational viral epitopes. However, a more efficient and cost-effective adjuvant than those currently used is needed. Immunostimulant-Particle Adjuvant (ISPA) is an Immune Stimulating Complex (ISCOM) - type adjuvant formulated with dipalmitoyl-phosphatidylcholine, cholesterol, stearylamine, alpha tocopherol and QuilA. In the present work, we have evaluated the immune response against FMDV using VLPs and ISPA as adjuvant. VLPs (serotype A/Arg/01) were obtained by transient gene expression in mammalian cell cultures, and a previously developed murine model, able to predict the ability of a vaccine to induce protection in cattle, was used for vaccination experiments in a first approach. The VLPs-ISPA vaccine induced protection in mice against challenge and elicited a specific antibody response in sera. In a second approach, the VLPs-ISPA vaccine was tested in calves. Interestingly one vaccine dose was enough to induce total α-FMDV antibodies , as measured by ELISA, as well as neutralizing Abs. Antibody titers reached an Expected Percentage of Protection higher than 90%. The EPP index calculates the probability that livestock will be protected against a challenge of 10.000 bovine infectious doses after vaccination. Moreover, IFN-γ levels secreted in vitro by mononuclear cells of VLP-ISPA vaccinated animals were significantly higher (p <0.05) than in the non-adjuvanted VLPs group. Overall, the results demonstrate that VLPs and ISPA are a promising combination for the development of a novel FMD vaccine, since no infectious FMDV is used and a protective immune response can be induced in calves, comparable to that achieved with the commercial FMDV vaccine.