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Updated: Apr 13, 2026

Development and Validation of an Ultrasensitive Single Molecule Array Digital Enzyme-linked Immunosorbent Assay for Human Interferon-α
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Structural Insights into the Neutralization Properties of the Fully Human, Anti-interferon Monoclonal Antibody

Vaheh Oganesyan1, Li Peng2, Robert M Woods2

  • 1From the Department of Antibody Discovery and Protein Engineering, MedImmune LLC, Gaithersburg, Maryland 20878 oganesyanv@medimmune.com.

The Journal of Biological Chemistry
|May 1, 2015
PubMed

We report the three-dimensional structure of human interferon α-2A (IFN-α2A) bound to the Fab fragment of a therapeutic monoclonal antibody (sifalimumab; IgG1/κ). The structure of the corresponding complex was solved at a resolution of 3.0 Å using molecular replacement and constitutes the first reported structure of a human type I IFN bound to a therapeutic antibody. This study revealed the major contribution made by the first complementarity-determining region in each of sifalimumab light and heavy chains. These data also provided the molecular basis for sifalimumab mechanism of action. We propose that its interferon-neutralizing properties are the result of direct competition for IFN-α2A binding to the IFN receptor subunit 1 (IFNAR1) and do not involve inhibiting IFN-α2A binding to the IFN receptor subunit 2 (IFNAR2).

Keywords:
autoimmune disease, epitope mapping, interferon, monoclonal antibody, nuclear magnetic resonance (NMR), protein expression, sifalimumab, structural biology, systemic lupus erythematosus, x-ray crystallography

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