Inactivation of foot-and-mouth disease virus vaccine strains by activation of virus-associated endonuclease

Abstract

A new inactivation process for foot-and-mouth disease virus (FMDV) has been developed. This process is based on the activation of the FMDV endonuclease by incubation of unfractionated viral suspension or purified virions at 37 degrees C in the presence of high concentrations of monovalent cations such as K+, Cs+ or NH4+ at pH 8.5. This procedure completely inactivated several FMDV vaccine strains yielding preparations having similar amounts of 140S particles to untreated controls. The inactivation followed first-order kinetics and the rate of inactivation was faster than that achieved with other agents, e.g. binary ethyleneimine. Testing in suckling mice or tissue culture revealed no residual infectivity after inactivation. Virus particles purified from inactivated preparations showed (i) the same sedimentation coefficient as non-inactivated preparations, (ii) electrophoretic patterns of their viral capsid proteins identical to those derived from non-inactivated preparations, and (iii) extensive degradation of the 35S viral RNA. This method is safer than inactivation with aziridines because only innocuous chemicals are used in the process.