Virucidal Treatment of Blood Protein Products with UVC Radiation

Abstract

The virus safety of blood derivatives continues to be of concern, especially with respect to nonenveloped and/or heat-stable viruses. Previously, we demonstrated that treatment of whole plasma, AHF concentrate or fibrinogen with short wavelength ultraviolet light (UVC) results in the inactivation of > or = 10(6) infectious doses (ID) of encephalomyocarditis virus (EMCV), hepatitis A virus (HAV) and porcine parvovirus (PPV), each of which is nonenveloped. Protein recovery was enhanced greatly by inclusion of the flavonoid, rutin, added prior to UVC exposure to quench reactive oxygen species. We now report on the treatment of albumin and intravenous immune globulin (IVIG) isolated by a previously described, integrated chromatographic method. Albumin was treated with either 0.1 or 0.2 J/cm2 UVC in the presence of 0.8 or 1.6 mM rutin; IVIG was treated with either 0.05 or 0.1 J/cm2 UVC in the presence of 0.5 or 1.0 mM rutin. Our results show that > or = 10(6.9) ID of EMCV and PPV were inactivated under each of the conditions studied except the treatment of albumin with 0.1 J/cm2 UVC in the presence of 1.6 mM rutin where 10(4.3) ID of EMCV and > or = 10(6.9) ID of PPV were killed. It appears that the sensitivity of PPV to UVC exceeds that of EMCV and that virus kill with UVC is higher in IVIG than in albumin. In the absence of rutin, UVC increased the extent of aggregation of both albumin and IVIG by two- to three-fold. With rutin present, the increase in albumin aggregation was reduced, and it was virtually eliminated by subsequent processing on Sephacryl S-200, a step in the existing procedure designed to remove aggregates. The increase in aggregation of IVIG appeared to be eliminated on inclusion of either 0.5 mM or 1 mM rutin. We conclude that both albumin and IVIG can be treated with UVC to inactivate > or = 10(6) ID of nonenveloped viruses. The inclusion of rutin during treatment helps protect against protein aggregation.

Proteomic analysis of UVC irradiation‐induced damage of plasma proteins: Serum amyloid P component as a major target of photolysis

“…Therefore, procedures for inactivating pathogenic viruses in these products are mandatory. Recently, however, it has received renewed attention for its capability to inactivate physically resistant non-enveloped singlestranded viruses such as Hepatitis A and parvovirus B19 [5,6]. Ultraviolet irradiation was one of the first methods investigated in the pioneering years of biopharmaceutical plasma fractionation, but soon proved ineffective at preventing transmission of ''serum hepatitis'' [4].…”

Pyrimidine Dimer Formation and Oxidative Damage in M13 Bacteriophage Inactivation by Ultraviolet C Irradiation¶

“…nonenveloped and thermoresistant viruses (2,3). Several studies have reported that the use of UV-C radiation is a promising approach to the inactivation of nonenveloped viruses in plasma-fractionated products (4)(5)(6). UV-C has been known to produce lesions in DNA, predominantly cyclobutane pyrimidine dimers (CPD) and pyrimidine pyrimidone photoproducts ((6-4)PP), which are responsible for cell death (7,8), mutations (9,10) and carcinogenesis (11,12).…”

Protective effect of nicotinic acid on human albumin during UV-C irradiation

“…In particular, continuous-flow UV-C devices operating at 254 nm have been designed and their ability to eliminate viruses accurately tested [6][7][8]. The virucidal effect of UV-C radiations (100-280 nm) is due to their inherent capacity to induce the dimerization of adjacent pyrimidines in DNA and RNA, preventing subsequent replication and transcription.…”