Enhancement in the Safety of Immune Globulins Prepared from High-Risk Plasma

Hyperimmune γ-globulins have proven efficacious in the prevention and treatment of viral infections, including those caused by hepatitis A and B viruses, cytomegalovirus, parvovirus. Interest in the prevention and/or treatment of infections caused by human immunodeficiency virus (HIV) has led to clinical trials with anti-HIV immune plasma and purified immune globulin prepared from donors who are actively infected with HIV. The handling and fractionation of this or other infectious plasma requires the construction and operation of virus containment facilities designed to protect fractionation employees and the immediate environment. This requirement would be reduced substantially by applying virucidal procedures prior to or during plasma pooling. We have shown that heating plasma at 56°C for 1 h followed by treatment with 1% tri(n-butyl) phophate (TNBP) and 1% Triton X-100 for 4 h at 30°C resulted in the inactivation of ≥ 10^12.1 tissue culture infectious doses (TCID₅₀) of HIV. With this treatment, the recovery of IgG was 87±3%. Fractionation of treated plasma by cold ethanol precipitation proceeded normally, and overall recovery, purity, and potency against selected viral markers were unaffected. The additional treatment of plasma with 15 g/l Aerosil for 4 h at 45 °C removed 10^4.5 TCID₅₀ of HIV but resulted in substantial IgG losses both prior to and following fractionation. We conclude that potentially infectious plasma can be treated at 56°C for 1 h and by TNBP/Triton X-100 at 30°C for 4 h prior to fractionation. These steps appear sufficient to assure safety and to permit routine fractionation of plasma. Aerosil treatment, under the condition evaluated, was less satisfactory, although lower concentrations or temperatures than those evaluated may prove advantageous.