Antibody recognition of a highly conserved influenza virus epitope: implications for universal prevention and therapy

By D. Ekiert, G. Bhabha, M. Elsliger, R. Friesen, M. Jongeneelen, M. Throsby, J. Goudsmit, Ian A. Wilson. 2009

1,369 citations recorded by the source corpus.

Influenza virus presents an important and persistent threat to public health worldwide, and current vaccines provide immunity to viral isolates similar to the vaccine strain. High-affinity antibodies against a conserved epitope could provide immunity to the diverse influenza subtypes and protection against future pandemic viruses. Cocrystal structures were determined at 2.2 and 2.7 angstrom resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with the major surface antigen (hemagglutinin, HA) from viruses responsible for the 1918 H1N1 influenza pandemic and a recent lethal case of H5N1 avian influenza. In contrast to other structurally characterized influenza antibodies, CR6261 recognizes a highly conserved helical region in the membrane-proximal stem of HA1 and HA2. The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion. The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.

Subfields: Epidemiology, Radiology, Nuclear Medicine and Imaging

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

In Radiology, Nuclear Medicine and Imaging

Citations in the corpus

Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen (2017, background): “Notably, the identification of stem-directed antibodies against influenza HA (35) represented a paradigm shift in the approach to develop a universal influenza vaccine, with recent studies demonstrating substantial promise (33, 34).”
Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers (2020, neutral): “cellular cytotoxicity (ADCC) responses [3, 7-9].”
A perspective on the structural and functional constraints for immune evasion: insights from the influenza virus (2017, background): “The problem of neutralizing group 2 influenza subtypes has been attributed to an N-glycosylation site at HA1 Asn38, which is immediately adjacent to the conserved epitope [99, 100] (Fig.”
Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin (2016, background): “To answer this question, we examined the inherent mutational tolerance of the largely overlapping epitopes of four broadly neutralizing anti-stalk antibodies: F10 [35], CR6261 [36], FI6v3 [37], and CR9114 [38].”
Next-Generation Influenza Vaccines. (2020, background): “Because the stem domain is largely conserved within given HA subtypes and to a lesser extent across subtypes, antibodies to this domain, particularly those targeting the hydrophobic groove surrounding the Trp21HA2 residue, exhibit neutralizing breadth against multiple subtype viruses within influenz”
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 ”