A Refined Guinea Pig Model of Foot-and-Mouth Disease Virus Infection for Assessing the Efficacy of Antiviral Compounds

Abstract

An antiviral containment strategy for foot-and-mouth disease (FMD) outbreaks could support or replace current contingency plans in case of an outbreak in Europe and could spare many healthy animals from being pre-emptively culled. Recently, substantial progress has been made towards the development of small molecule drugs that inhibit FMD virus (FMDV) replication in vitro. For the initial in vivo evaluation of antiviral lead molecules, a refined FMDV-infection model in guinea pigs (GP) is herewith described. This GP model was validated by demonstrating the antiviral effect of T-1105 (an influenza virus inhibitor with reported activity against FMDV). Sixteen animals were orally administered with T-1105 twice daily (400 mg/kg/day) for five consecutive days and inoculated intraplantarly with 100 GPID50 of the GP-adapted FMDV strain O1 Manisa 1 h after the first administration. The efficacy of T-1105 was compared with that of prophylactic vaccination with a highly potent double-oil emulsion-inactivated O1 Manisa vaccine. Ten animals received a single, full (2 ml) cattle vaccine dose and were inoculated 3 weeks later. Fourteen T-1105-treated and all vaccinated GP were completely protected from generalization of vesicular lesions. At 2 dpi, viral RNA was detected in serum of 9/16 T-1105-treated and of 6/10 vaccinated animals. At 4 dpi, viral RNA was detected in serum, organs and oral swabs of half of the T-1105-treated animals and only in the serum of 1/10 of the vaccinated animals. Mean viral RNA levels in serum and organs of T-1105-treated and vaccinated animals were reduced compared to untreated controls (P < 0.01). T-1105 conferred a substantial clinical and virological protection against infection with O1 Manisa, similar to the protection afforded by vaccination. These results validate the suitability of the enhanced GP model for the purpose of initial evaluation of inhibitors of FMDV replication and illustrate the potential of selective inhibitors of viral replication to control FMD outbreaks.

In vitro Adaptation, Molecular Characterization and Tissue Tropism of Foot-and-mouth Disease Virus in Guinea Pigs

“…GPID 50 of the virus was recorded as 10 5.3 /ml. The results are in agreement with the findings of De Vleeschauwer et al, (2016) who used guinea pigs to access antiviral compound activity against FMD.…”

Favipiravir and Its Structural Analogs: Antiviral Activity and Synthesis Methods

“…The efficacy of 3-hydroxypyrazine-2-carboxamide and the prophylactic O1 Manisa vaccine against the foot-and-mouth disease virus was also compared in a guinea pig model. The efficacy of prophylactic therapy with T-1105 (guinea pigs, 400 mg/kg/day orally for 5 days) was shown to be comparable to that of animal vaccination [ 57 ].…”

Global Foot-and-Mouth Disease Research Update and Gap Analysis: 5 - Biotherapeutics and Disinfectants

“…In another study, the nucleoside analogue 2 0 -C-methylcytidine (2 0 CMC) prevented the establishment of FMDV infection in severe combined immunodeficient mice (Lefebvre et al, 2014a). Seeking improved models for in vivo assessment of candidate molecules, the same group have developed a refined approach in guinea pigs for assessing anti-FMDV biotherapeutics and shown promising preliminary results (De Vleeschauwer et al, 2016).…”