Diverse antigenic site targeting of influenza hemagglutinin in the murine antibody recall response to A(H1N1)pdm09 virus

Virology. 2015 Nov:485:252-62. doi: 10.1016/j.virol.2015.08.004. Epub 2015 Aug 27.

Abstract

Here we define the epitopes on HA that are targeted by a group of 9 recombinant monoclonal antibodies (rmAbs) isolated from memory B cells of mice, immunized by infection with A(H1N1)pdm09 virus followed by a seasonal TIV boost. These rmAbs were all reactive against the HA1 region of HA, but display 7 distinct binding footprints, targeting each of the 4 known antigenic sites. Although the rmAbs were not broadly cross-reactive, a group showed subtype-specific cross-reactivity with the HA of A/South Carolina/1/18. Screening these rmAbs with a panel of human A(H1N1)pdm09 virus isolates indicated that naturally-occurring changes in HA could reduce rmAb binding, HI activity, and/or virus neutralization activity by rmAb, without showing changes in recognition by polyclonal antiserum. In some instances, virus neutralization was lost while both ELISA binding and HI activity were retained, demonstrating a discordance between the two serological assays traditionally used to detect antigenic drift.

Keywords: A/H1N1/pdm09; Antigenic drift; Antigenic site; Epitope mapping; Influenza; Monoclonal antibody; Virus neutralization.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Viral / immunology*
  • Antigenic Variation / genetics
  • Antigenic Variation / immunology*
  • Antigens, Viral / chemistry
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Binding Sites
  • Cross Reactions / immunology
  • Epitope Mapping
  • Epitopes / chemistry
  • Epitopes / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immunologic Memory*
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / virology
  • Mice
  • Models, Molecular
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / virology
  • Protein Binding
  • Protein Conformation
  • Recombinant Proteins

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Antigens, Viral
  • Epitopes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Recombinant Proteins