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Related Concept Videos

Influenza01:27

Influenza

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Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...
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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
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A common solution to group 2 influenza virus neutralization.

Robert H E Friesen1, Peter S Lee, Esther J M Stoop

  • 1Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 2333 CN, Leiden, The Netherlands.

Proceedings of the National Academy of Sciences of the United States of America
|December 17, 2013
PubMed
Summary

Researchers discovered a new broadly neutralizing antibody (bnAb), CR8043, targeting group 2 influenza A viruses. This finding advances monoclonal antibody (mAb) immunotherapy and universal influenza vaccine development.

Keywords:
X-ray crystallographyantibody recognitionelectron microscopy

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Area of Science:

  • Immunology
  • Virology
  • Structural Biology

Background:

  • Broadly neutralizing antibodies (bnAbs) are crucial for developing universal influenza vaccines and monoclonal antibody (mAb)-based immunotherapies.
  • A previously identified human bnAb, CR8020, targets group 2 influenza A viruses by binding to a conserved epitope on the hemagglutinin (HA) stem.
  • This epitope is associated with neutralizing activity against H3, H7, and H10 influenza virus subtypes.

Purpose of the Study:

  • To report the discovery and characterization of a second human bnAb, CR8043, targeting group 2 influenza A viruses.
  • To investigate the binding site and neutralizing capabilities of CR8043 against influenza viruses.
  • To explore the potential of the conserved HA stem epitope for therapeutic and vaccine design.

Main Methods:

  • Isolation and characterization of a novel broadly neutralizing antibody (bnAb), CR8043.
  • In vitro neutralization assays against influenza virus strains.
  • Protection studies in mice challenged with lethal influenza virus doses.
  • Determination of the crystal structure and cryo-electron microscopy (cryo-EM) reconstructions of the CR8043-hemagglutinin (HA) complex.

Main Results:

  • CR8043, derived from a distinct germ-line gene, exhibits neutralizing activity against H3 and H10 influenza viruses in vitro.
  • CR8043 provides protection in mice against lethal H3N2 and H7N7 influenza virus challenge.
  • Structural analysis revealed that CR8043 binds to the HA stem epitope, similar to CR8020, but via an alternative binding mode and distinct interactions.

Conclusions:

  • The identification of CR8043 confirms the HA stem as a conserved site of vulnerability on group 2 influenza A viruses.
  • This conserved epitope holds significant potential for the rational design of universal influenza vaccines and novel mAb-based therapeutics.
  • The distinct binding characteristics of CR8043 offer new insights for antibody-based influenza strategies.