An Adenovirus Vector Expressing FMDV RNA Polymerase Combined with a Chimeric VLP Harboring a Neutralizing Epitope as a Prime Boost Strategy to Induce FMDV-Specific Humoral and Cellular Responses

Abstract

Foot and mouth disease is a highly contagious disease affecting cattle, sheep, and swine among other cloven-hoofed animals that imposes serious economic burden by its direct effects on farm productivity as well as on commerce of farmed produce. Vaccination using inactivated viral strains of the different serotypes is an effective protective measure, but has several drawbacks including a lack of cross protection and the perils associated with the large-scale growth of infectious virus. We have previously developed chimeric virus-like particles (VLPs) bearing an FMDV epitope which induced strong specific humoral responses in vaccinated pigs but conferred only partial protection against homologous challenge. While this and other FMD vaccines under development mostly rely on the induction of neutralizing responses, it is thought that induction of specific T-cell responses might improve both cross protective efficacy as well as duration of immunity. Therefore, we here describe the development of a recombinant adenovirus expressing the highly conserved nonstructural FMDV 3D protein as well as its capacity to induce specific T-cell responses in a murine model. We further describe the generation of an FMDV serotype C-specific chimeric VLP and analyze the immunogenicity of two different prime-boost strategies combining both elements in mice. This combination can effectively induce both humoral and cellular FMDV-specific responses eliciting high titers of ELISA and neutralizing antibodies anti-FMDV as well as a high frequency of IFNγ-secreting cells. These results provide the basis for further testing of this anti FMD vaccination strategy in cattle or pig, two of the most relevant natural host of this pathogen.