SFTSV Gn-Head mRNA vaccine confers efficient protection against lethal viral challenge

J Med Virol. 2023 Nov;95(11):e29203. doi: 10.1002/jmv.29203.

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus, causing thrombocytopenia and hemorrhagic fever, with a fatality rate ranging from 12% to 30%. SFTSV possesses Gn and Gc glycoproteins, which are responsible for host cell receptor attachment and membrane fusion, respectively, to infect host cells. We have previously reported a protein subunit vaccine candidate (sGn-H-FT) of the SFTSV soluble Gn head region (sGn-H) fused with self-assembling ferritin (FT) nanoparticles, displaying strong protective immunogenicity. In this study, we present messenger RNA (mRNA) vaccine candidates encoding sGn-H or sGn-H-FT, both of which exhibit potent in vivo immunogenicity and protection capacity. Mice immunized with either sGn-H or sGn-H-FT mRNA lipid nanoparticle (LNP) vaccine produced strong total antibodies and neutralizing antibodies (NAbs) against sGn-H. Importantly, NAb titers remained high for an extended period. Finally, mice immunized with sGn-H or sGn-H-FT mRNA LNP vaccine were fully protected from a lethal dose of SFTSV challenge, showing no fatality. These findings underscore the promise of sGn-H and sGn-H-FT as vaccine antigen candidates capable of providing protective immunity against SFTSV infection.

Keywords: Gn-H; ferritin nanoparticle; mRNA vaccine; severe fever with thrombocytopenia syndrome virus; tick-borne virus.

Publication types

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

MeSH terms

  • Animals
  • Mice
  • Phlebovirus* / genetics
  • RNA, Messenger / genetics
  • Vaccines, Synthetic
  • Viral Envelope Proteins* / genetics
  • mRNA Vaccines

Substances

  • Viral Envelope Proteins
  • Vaccines, Synthetic
  • RNA, Messenger