Freedom from Transmission of Hepatitis‐B of Gamma‐Globulin and Heat‐Inactivated Plasma Protein Fraction Prepared from Contaminated Human Plasma by Fractionation with Solid‐Phase Polyelectrolytes1

Abstract

Plasma contaminated with hepatitis B surface antigen (HBsAg) and infectious when injected in a dilution of 1:1,000,000 in chimpanzees was fractionated by a solid-phase polyelectrolyte (PE) procedure for its content of plasma protein fraction (PPF) and .gamma.-globulin (immune serum globulin; ISG). Quantitative Ausria II radioimmunoassays showed that nearly 1/2 the HBsAg was bound by the PE and could be eluted at low pH, while the rest was found in the heat-inactivated PPF. When the ISG was concentrated to 16%, the 13 mg/kg (comparable to a human dose) was injected i.m. in 6 chimpanzees or when the PPF was heated at 60.degree. C for 10 h and injected i.v. in 2 chimpanzees there was no clinical or laboratory evidence of hepatitis B infection after 12 mo., although 1 chimp of 2 who received the same material showed a borderline positive anti-HBsAg antibody result on 1 of 52 weekly serum samples. Since the new PE fractionation method is essentially nondenaturing and simpler than the classical ethanol procedures, it was important to establish the noninfectivity of the final products.