Neutralization of influenza A viruses by insertion of a single antibody loop into the receptor binding site
By D. Ekiert, A. Kashyap, J. Steel, Adam M. Rubrum, G. Bhabha, R. Khayat, J. H. Lee, Michael A. Dillon, Ryann O'Neil, Aleksandr M. Faynboym and 8 more. 2012
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Immune recognition of protein antigens relies on the combined interaction of multiple antibody loops, which provide a fairly large footprint and constrain the size and shape of protein surfaces that can be targeted. Single protein loops can mediate extremely high-affinity binding, but it is unclear whether such a mechanism is available to antibodies. Here we report the isolation and characterization of an antibody called C05, which neutralizes strains from multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and electron microscopy structures show that C05 recognizes conserved elements of the receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of the haemagglutinin receptor-binding site is dominated by a single heavy-chain complementarity-determining region 3 loop, with minor contacts from heavy-chain complementarity-determining region 1, and is sufficient to achieve nanomolar binding with a minimal footprint. Thus, binding predominantly with a single loop can allow antibodies to target small, conserved functional sites on otherwise hypervariable antigens.
Subfields: Epidemiology, Radiology, Nuclear Medicine and Imaging
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Citations in the corpus
- Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site (2015, unknown): “MAbs CH65 (Whittle et al., 2011), C05 (Ekiert et al., 2012), and some others neutralize influenza A viruses through the conserved sialic acid-binding site on a viral hemagglutinin.”
- Next-Generation Influenza Vaccines. (2020, background): “…are also regarded as improved vaccine targets, inspired by highly neutralizing human nAbs targeting the receptor-binding site (Whittle et al. 2011; Ekiert et al. 2012; Lee et al. 2014; Schmidt et al. 2015; Shen et al. 2017) and the lateral patch or the vestigial esterase domain of the head…”