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Neutralization of Human IFN-Alpha Subtypes with Monoclonal Antibodies

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A number of antibodies raised against human interferon alpha (IFN-α) have been reported. We have characterized the binding to a panel of interferon alpha subtypes and some of their alleles by direct binding ELISA. Additionally, the binding to these subtypes in a pairwise manner has also been determined. For these antibody pairs, the correlation between direct- and solution-binding characteristics is good. We have also determined the ability of these monoclonals to bind to IFN which is prebound to the interferon receptor chain 2 (IFNAR2). Most of the neutralizing antibodies will bind to blockade of IFNAR2. When the ability of the MAbs to neutralize the various subtypes of IFN-α is examined we found that the MAbs do not neutralize subtypes to which they bind poorly. Although a particular MAb appears to bind well to several subtypes, it does not neutralize all of those subtypes. This discrepancy might be explained by kinetics of binding or due to the ability of the different subtypes to interact differentially with the receptor complex on cells.

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Binding and Neutralization of MAbs to Human IFN-Alpha Subtypes



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