Monoclonal antibody against H1N1 influenza virus hemagglutinin cross reacts with hnRNPA1 and hnRNPA2/B1

Mol Med Rep. 2020 Nov;22(5):3969-3975. doi: 10.3892/mmr.2020.11494. Epub 2020 Sep 7.

Abstract

Following influenza A vaccination, certain individuals exhibit adverse reactions in the nervous system, which causes a problem with the safety of the influenza A vaccine. However, to the best of our knowledge, the underlying mechanism of this is unknown. The present study revealed that a monoclonal antibody (H1‑84mAb) against the H1N1 influenza virus hemagglutinin (HA) protein cross‑reacted with an antigen from brain tissue. Total brain tissue protein was immunoprecipitated with this cross‑reactive antibody, and mass spectrometry revealed that the bound antigens were heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and hnRNPA2/B1. Subsequently, the two proteins were expressed in bacteria and it was demonstrated that H1‑84mAb bound to hnRNPA1 and hnRNPA2/B1. These two proteins were expressed in three segments and the cross‑reactivity of H1‑84mAb with the glycine (Gly)‑rich domains of hnRNPA1 (195aa‑320aa) and hnRNPA2/B1 (202aa‑349aa) was determined using ELISA blocking experiments. It was concluded that the Gly‑rich domains of these two proteins are heterophilic antigens that cross‑react with influenza virus HA. The association between the heterophilic antigen Gly‑rich domains and the safety of influenza A vaccines remains to be investigated.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism*
  • Brain / metabolism
  • Hemagglutinins / immunology
  • Heterogeneous Nuclear Ribonucleoprotein A1 / chemistry
  • Heterogeneous Nuclear Ribonucleoprotein A1 / metabolism*
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / chemistry
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / metabolism
  • Male
  • Protein Domains
  • Rats

Substances

  • Antibodies, Monoclonal
  • Hemagglutinins
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Hnrnpa1 protein, rat
  • Influenza Vaccines
  • hnRNP A2