ISPA cage-like particle adjuvant enhances protection induced by
A/Arg/2001 Foot and Mouth Disease Virus-Like Particles
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.