Interferon-alpha neutralizing antibodies in HIV and chronic HCV patients treated with natural-source human leukocyte-derived interferon-alpha n3.
Human leukocyte-derived IFN-alpha n3 (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-alpha n3. Among 69 HCV refractory patients who were unresponsive to previous treatment with rIFN-alpha 2b, 2 had neutralizing antibodies to rIFN-alpha 2b prior to IFN-alpha n3 therapy, with no or limited cross-reactivity to IFN-alpha n3. After retreatment with IFN-alpha n3, both patients had detectable neutralizing titers to IFN-alpha n3. Additionally, 2 other patients developed low and transient neutralizing titers to IFN-alpha n3. Interferon subtype specificity of these antibodies was tested against RP-HPLC purified fractions of IFN-alpha n3, as well as rIFN-alpha 2b and rIFN-alpha 8b. Sera from patients previously treated with rIFN-alpha 2b with high antibody titers to rIFN-alpha 2b strongly reacted with the natural IFN-alpha 2b, and to a limited extent with other iFN-alpha subtypes. Neutralizing activity against IFN-alpha 2b was significantly competed out by the presence of a small amount of other interferon subtypes present in IFN-alpha n3. One patient with prior presence of antibodies to IFN-alpha 2b developed a high antibody titer to IFN-alpha 8b with limited reactivity to IFN-alpha n3. Two of the HCV refractory patients with prior neutralizing antibodies to rIFN-alpha 2b responded to IFN-alpha n3 therapy. These data suggest that the presence of neutralizing antibodies to individual IFN-alpha species will not significantly diminish the biological activity and the clinical efficacy of multi-species IFN-alpha n3.
Zhao
X X
XX
Interferon Sciences, New Brunswick, NJ 08901-3605, USA.
Hua
J
J
Smith
T
T
Ferencz-Biro
K
K
Liao
M J
MJ
Rashidbaigi
A
A
D000906:Antibodies / Q000097:blood; D000918:Antibody Specificity; D002908:Chronic Disease; D003429:Cross Reactions; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D006526:Hepatitis C / Q000276:immunology* / Q000628:therapy; D006801:Humans; D016898:Interferon-alpha / Q000145:classification / Q000276:immunology* / Q000627:therapeutic use*; D009500:Neutralization Tests
D000906:Antibodies; D016898:Interferon-alpha