Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin

Science. 2018 Nov 2;362(6414):598-602. doi: 10.1126/science.aaq0620.

Abstract

Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / ultrastructure
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / ultrastructure
  • Camelids, New World / immunology*
  • Crystallography, X-Ray
  • Dogs
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / genetics
  • Immunodominant Epitopes / immunology
  • Influenza A virus / immunology*
  • Influenza B virus / immunology*
  • Influenza Vaccines / immunology*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Orthomyxoviridae Infections / prevention & control*
  • Peptide Library
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Single-Domain Antibodies

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunodominant Epitopes
  • Influenza Vaccines
  • Peptide Library
  • Recombinant Proteins
  • Single-Domain Antibodies