A cross-reactive mouse monoclonal antibody against rhinovirus mediates phagocytosis in vitro

Sci Rep. 2020 Jun 16;10(1):9750. doi: 10.1038/s41598-020-66600-x.

Abstract

Rhinoviruses (RVs) are the main cause of the common cold worldwide. To date, more than 160 types of the virus have been recognized, categorized into three major species - A, B, and C. There are currently no approved vaccines available to prevent infection with RVs. To elicit antibodies against conserved regions located on capsid proteins of RV A viruses, mice were sequentially vaccinated with DNA plasmids encoding capsid proteins of different RV A types. After a final boost with whole virus, antibody-expressing hybridomas were generated. After isotyping, 11 monoclonal antibodies (mAbs) expressing an IgG subtype Fc-domain were selected for further expansion and purification. Three mAbs showed cross-reactivity against multiple strains of RV A viruses by ELISA, including strains A1A, A1B, A15, A16 and A49. Other mAbs had strain-specific binding patterns, with the majority of mAbs showing reactivity to RV-A15, the strain used for the final vaccination. We found that the RV-A15-specific mAbs, but not the cross-reactive mAbs, had neutralizing activity against RV-A15. An antibody dependent cellular phagocytosis (ADCP) assay revealed substantial ADCP activity for one of the cross-reactive mAbs. Epitope mapping of the neutralizing mAbs via escape mutant virus generation revealed a shared binding epitope on VP1 of RV-A15 for several neutralizing mAbs. The epitope of the ADCP-active, non-neutralizing mAb was determined by microarray analysis of peptides generated from the VP1 capsid protein. VP1-specific, cross-reactive antibodies, especially those with ADCP activity, could contribute to protection against RV infections.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Capsid Proteins / immunology
  • Common Cold / immunology*
  • Cross Reactions / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Epitope Mapping
  • Humans
  • Hybridomas / immunology
  • Mice
  • Phagocytosis / immunology
  • Phagocytosis / physiology
  • Rhinovirus / genetics
  • Rhinovirus / immunology*
  • Viral Proteins / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Capsid Proteins
  • Viral Proteins