A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses

By D. Ekiert, R. Friesen, G. Bhabha, Ted H. J. Kwaks, M. Jongeneelen, Wenli Yu, C. Ophorst, F. Cox, Hans J. W. M. Korse, Boerries Brandenburg and 10 more. 2011

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An antibody against a conserved epitope broadly neutralizes group 2 influenza viruses. Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of VH1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the VH1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.

Subfields: Epidemiology, Molecular Biology, Radiology, Nuclear Medicine and Imaging

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Citations in the corpus

Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes (2016, background): “In contrast, the group 2-neutralizing antibodies CR8020 and CR8043 (Ekiert et al., 2011; Friesen et al., 2014) recognize a different region of the fusion peptide and a small b sheet below it in the fusion domain (Figure 7B, red box).”
Next-Generation Influenza Vaccines. (2020, background): “…subtype viruses within influenza A group 1 subtypes (Okuno et al. 1993; Throsby et al. 2008; Ekiert et al. 2009; Sui et al. 2009), group 2 subtypes (Ekiert et al. 2011; Friesen et al. 2014), or across both group 1 and group 2 subtypes (Corti et al. 2011; Nakamura et al. 2013; Joyce et al. 2016;…”
Multistate design of influenza antibodies improves affinity and breadth against seasonal viruses (2019, background): “One such antibody, C05, has remarkable breadth of recognition of HAs from certain strains within both group 1 and group 2 viruses, and interacts with the HA molecule by using a single antibody hypervariable loop (8).”
Conserved Neutralizing Epitope at Globular Head of Hemagglutinin in H3N2 Influenza Viruses (2014, methodology): “Preparation of MAbs.”
Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers (2020, methodology): “HA ectodomain trimers were expressed as shown schematically in Fig 1A with a C-terminal foldon trimerization domain, 13-residue SpyTag [20], and a 6x-His (modified from HA constructs in [22] to include a SpyTag).”
Quantifying B cells capable of producing broadly neutralizing antibodies against influenza serves as a metric to guide the development of a universal influenza vaccine (2016, positive): “Neutralization breadth and potency for this set of immunoglobulins were similar to that of antibody CR9114 (Figure S4; Table S4), neutralizing all common human-infecting subtypes of influenza A except H2 and exceeding substantially the breadth of group 1-specific or group 2-specific stem antibodies ”