An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus

PLoS Pathog. 2019 Feb 1;15(2):e1007375. doi: 10.1371/journal.ppat.1007375. eCollection 2019 Feb.

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies, Neutralizing / metabolism*
  • Antibodies, Neutralizing / physiology
  • Antibodies, Viral / metabolism
  • Bunyaviridae Infections / therapy
  • Epitopes / immunology
  • Female
  • Fever
  • Glutamine / immunology
  • Glutamine / metabolism
  • Glycoproteins / immunology
  • HEK293 Cells
  • Humans
  • Leukopenia
  • Male
  • Mice
  • Mice, Knockout
  • Neutralization Tests
  • Phlebovirus / immunology*
  • Phlebovirus / pathogenicity
  • Republic of Korea
  • Thrombocytopenia / immunology
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Glycoproteins
  • Viral Envelope Proteins
  • Glutamine

Supplementary concepts

  • SFTS phlebovirus

Grants and funding

This research was supported by the Commercialization Promotion Agency for Research and Development outcomes (COMPA), the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT (MSIT), Republic of Korea (grant number: 2017K000459, 2017M3A9G6068245). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.