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.