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Cross-reactivity00:42

Cross-reactivity

Overview

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Related Experiment Video

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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
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Allosteric Neutralization by Human H7N9 Antibodies.

Manxue Jia1, Hanjun Zhao2,3, Nicholas C Morano4,5

  • 1Aaron Diamond AIDS Research Center, Affiliate of Rockefeller University, New York, NY 10016, USA.

Research Square
|November 21, 2023
PubMed
Summary

New monoclonal antibodies (mAbs) targeting the H7 hemagglutinin (HA) show promise for treating H7N9 avian influenza. Combining HA1- and HA2-directed mAbs provides enhanced protection against lethal H7N9 infection.

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Area of Science:

  • Virology
  • Immunology
  • Structural Biology

Background:

  • Avian influenza A virus H7N9 causes severe human infections with high fatality rates.
  • Current treatments for H7N9 are limited, with no specific human prevention or therapies available.

Approach:

  • Isolated four H7 hemagglutinin (HA)-reactive monoclonal antibodies (mAbs) from a convalescent H7N9 case.
  • Utilized cryo-electron microscopy (cryo-EM) to determine the structures of mAb-HA interactions.
  • Engineered an HA2-directed mAb for enhanced Fc effector function.

Key Points:

  • Two HA1-directed mAbs (H7.HK1, H7.HK2) potently neutralized H7N9 and protected mice from lethal challenge by disrupting viral entry.
  • H7.HK2 demonstrated sustained efficacy against later H7N9 isolates, indicating a conserved epitope.
  • An HA2-directed mAb (H7.HK4), while lacking neutralizing activity, conferred protection when engineered for Fc effector function and augmented protection when combined with H7.HK2.

Conclusions:

  • Monoclonal antibodies targeting distinct regions of H7 HA offer therapeutic potential against H7N9 avian influenza.
  • A combination strategy using neutralizing HA1-directed and Fc-enhanced HA2-directed mAbs provides augmented protection via an allosteric neutralization mechanism.