Inactivation of the hutchinson strain of non‐A, non‐B hepatitis virus by combined use of β‐propiolactone and ultraviolet irradiation

Abstract

A beta-propiolactone/ultraviolet irradiation procedure (beta PL/UV) has been evaluated for its ability to inactivate 30,000 chimpanzee infectious doses of the Hutchinson strain of non-A, non-B (NANB) virus. The chimpanzees were inoculated with plasma to which this dose of the titrated virus had been added prior to application of the beta PL/UV process in accordance with a procedure used for licensed blood derivatives in Germany. Neither animal developed hepatitis. When subsequently challenged with the same contaminated plasma, which had not been sterilized, both animals promptly developed typical NANB hepatitis. This study extends the high (approximately 10(7)-fold) process efficiency of the beta PL/UV procedure previously reported for hepatitis B virus to a blood-borne NANB virus.

Inactivation of the Hutchinson strain of hepatitis non‐A, non‐B virus in intravenous immunoglobulin by β‐propiolactone

“…A potential contribution of hepatitis non-A, non-B virus-neutralizing antibodies to the result of this study cannot be ruled out totally, as immunoglobulins are produced from pools of more than 1, OOO donations. However, the non-P-PL-treated, spiked immunoglobulin solution (control preparation) was fully infectious, and furthermore neutralizing antibodies against hepatitis non-A, non-B virus are estimated to be very rare and have not yet been detected despite extensive search in immunoglobulins, hyperimmunoglobulins, or reconvalescent sera [Prince et al, 1985b]. We therefore assume that the inactivation of hepatitis non-A, non-B virus in this study must be caused by the 0-PL treatment.…”

The Chimpanzee Model of Viral Hepatitis: Advances in Understanding the Immune Response and Treatment of Viral Hepatitis

“…The chimpanzee model was used to demonstrate that blood products were often contaminated with NANBH due to the use of large pools of plasma in manufacturing. Methods to inactivate the agent in blood products and render them safe for use in humans were based on infectivity studies in the chimpanzee, including UV light in the presence of beta-propiolactone ( Prince et al 1985 ) and solvent-detergent treatment ( Horowitz et al 1993 ; Prince et al 1984 , 1987 ). Long-term follow-up of chimpanzees and patients revealed that NANBH often induced chronic or persistent infections ( Bradley et al 1981 ), highlighting the need to develop methods to detect the virus and reduced transmission.…”

Intravenous Immunoglobulins: Evolution of Commercial IVIG Preparations

“…28,29 The emergence of HIV and reports of non-A, non-B hepatitis transmission by some IVIG products 30,31 caused manufacturers and regulatory agencies to examine existing IVIG manufacturing procedures for their capacity to eliminate viruses. [32][33][34][35][36][37][38][39][40][41] Development of dedicated virus inactivation procedures for IVIG production was also initiated. 42,43…”