A universal virus inactivant for decontaminating blood and biopharmaceutical products.

Abstract

Removal of virus infectivity from blood and biopharmaceutical products prepared from blood is an issue of considerable importance. Irrespective of the methods that are chosen it is vital that the biological activity of the product is not impaired. For blood and unfractionated plasma or serum, the problem is even more challenging. Selective inactivation of the genome is the key step in the preparation of killed virus vaccines. Imines have been used for more than 30 years for the preparation of inactivated foot-and-mouth disease virus vaccines without any evidence of survival of virus infectivity. Moreover, the immunogenicity of the virus is unimpaired. Viruses belonging to all the recognised families can be inactivated by imines. The biological properties of several proteins, including the cell growth-promoting factors in calf serum, are not impaired using conditions which ensure the inactivation of > 10(15) infectious units of poliovirus and foot-and-mouth disease virus (FMDV). Moreover, both viruses can be inactivated by imines at 4 degrees C, thus providing a method for removing infectivity from protein preparations which are unstable at higher temperatures. The mechanism by which FMDV is inactivated has been studied. We found that the RNA extracted from the virus after inactivation at 4 degrees C was not degraded and contained no hidden breaks but nevertheless was non-infectious. However, it could be amplified by PCR using primers corresponding to the gene coding for a portion of the viral RNA polymerase, but not from that coding for VP1, one of the structural proteins, showing that alteration of a base or bases had occurred in that region.