A UNIVERSAL VIRUS INACTIVANT FOR DECONTAMINATING BLOOD AND BIOPHARMACEUTICAL PRODUCTS

Removal of virus infectivity from blood and biopharmaceutical products prepared from blood is an issue of considerable importance. For bioph armaceutical products, removal can usually be achieved by a series of fractionation steps or by inactivation with a suitable reagent. Irresp ective 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 inact ivation of the genome is the key step in the preparation of killed vir us vaccines. Viruses belonging to ail the recognised families can be i nactivated by imines. In this paper it is shown that the biological pr operties of several proteins, including the cell growth-promoting fact ors in calf serum, are not impaired using conditions which ensure the inactivation of >10(15) infectious units of poliovirus and foot-and-mo uth disease virus (FMDV). Also shown is that both viruses can be inact ivated by imines at 4 degrees C, thus providing a method for removing infectivity from protein preparations which are unstable at higher tem peratures. The RNA extracted from FMDV inactivated at 4 degrees C was not degraded and contained no hidden breaks but nevertheless was non-i nfectious. However, it could be amplified by PCR using primers corresp onding to the gene coding for a portion of the viral RNA polymerase, b ut not from that coding for VP1, one of the structural proteins, showi ng that alteration oi a base or bases had occurred in that region. Sur prisingly, it could be translated in the rabbit reticulocyte system al though some of the products were different from those obtained with un modified RNA. (C) 1998 The International Association of Biological Sta ndardization.