Interferon-α neutralizing antibodies in HIV and chronic HCV patients treated with natural-source human leukocyte-derived interferon-αn3

Human leukocyte-derived IFN-αn3 (Alferon® N Injection) was administered subcutaneously to treat 20 patients with asymptomatic human immunodeficiency virus type 1 (HIV-1) and 141 patients with chronic hepatitis C virus (HCV) infections. The treatment of HIV-1 and HCV patients, previously untreated with any IFN preparations, did not result in development of neutralizing antibodies to IFN-αn3. Among 69 HCV refractory patients who were unresponsive to previous treatment with rIFN-α2b, 2 had neutralizing antibodies to rIFN-α2b prior to IFN-αn3 therapy, with no or limited cross-reactivity to IFN-αn3. After retreatment with IFN-αn3, both patients had detectable neutralizing titers to IFN-αn3. Additionally, 2 other patients developed low and transient neutralizing titers to IFN-αn3. Interferon subtype specificity of these antibodies was tested against RP-HPLC purified fractions of IFN-αn3, as well as rIFN-α2b and rIFN-α8b. Sera from patients previously treated with rIFN-α2b with high antibody titers to rIFN-α2b strongly reacted with the natural IFN-α2b, and to a limited extent with other IFN-α subtypes. Neutralizing activity against IFN-α2b was significantly competed out by the presence of a small amount of other interferon subtypes present in IFN-αn3. One patient with prior presence of antibodies ta IFN-α2b developed a high antibody titer to IFN-α8b with limited reactivity to IFN-αn3. Two of the HCV refractory patients with prior neutralizing antibodies to rIFN-α2b responded to IFN-αn3 therapy. These data suggest that the presence of neutralizing antibodies to individual IFN-α species will not significantly diminish the biological activity and the clinical efficacy of multi-species IFN-αn3.