A Novel Bioassay for the Determination of Neutralizing Antibodies to IFNβ1b

Abstract

We have adapted the new MxA gene-induction bioassay to measure neutralizing antibodies to interferon-β1b (IFN-β1b, the active ingredient in Betaseron®) in sera from patients treated with Betaseron®. This antibody assay has been validated to quantify neutralizing titers of 1:20 and above, with a precision of ± 0.20 in log₁₀. We have used this MxA gene-induction antibody assay to reinvestigate serum samples from multiple sclerosis (MS) patients treated with Betaseron®. The titers measured were closely comparable to those obtained in antiviral assays. Data obtained by both methods show that neutralizing antibodies may appear and subsequently disappear over time in the sera of some patients treated with Betaseron®. Sera from some patients contain binding antibodies to IFN-β1b. It was shown that binding antibody titers do not correlate quantitatively or qualitatively with neutralizing antibody titers, and indeed, a number of patients develop high levels of binding antibodies but never form measurable levels of neutralizing antibodies.