Identification of a candidate standard strain of severe fever with thrombocytopenia syndrome virus for vaccine quality control in China using a cross-neutralization assay

Biologicals. 2017 Mar:46:92-98. doi: 10.1016/j.biologicals.2017.01.005. Epub 2017 Feb 4.

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is caused by a phlebovirus of the Bunyaviridae family, which is designated as SFTS virus (SFTSV). To our knowledge, no efficient SFTSV vaccine exists. Here, we report the identification of a standard virus strain for the eight major SFTSV strains circulating in China for use in evaluating the SFTSV vaccine. Rabbits were immunized with the SFTSV strains and the cross-neutralization capacities of SFTSV anti-sera were determined in microculture cytopathic effect (CPE)-inhibition assays. The mean cross-neutralization capacity of the eight SFTSV anti-sera ranged from 62.4 to 142.6%, compared to autologous strains. The HB29 strain demonstrated strong cross-reactivity with heterologous antibodies, and 33 serum samples from SFTS patients efficiently neutralized HB29, suggesting its broad cross-reactivity. In addition, HB29 demonstrated good replication in Vero and MRC-5 cells (8.0 and 6.0 lg 50% cell culture-infectious dose/mL, respectively) and significant CPE, which satisfied the requirements for a standard virus strain. The HB29 isolate was proven identical to the reported HB29 strain by DNA sequencing, and showed high homology in the S segments with other SFTSV strains (94.8-99.7%). Our results suggest that HB29 may be the best candidate standard strain for use in SFTS vaccine development in China.

Keywords: CPE; NTAbs; Neutralizing antibodies; SFTS; SFTS virus; SFTSV; Severe fever with thrombocytopenia syndrome virus; Standard viral strain; Vaccine; cytopathic effect; neutralizing antibodies; severe fever with thrombocytopenia syndrome.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Asian People
  • Bunyaviridae Infections / ethnology
  • Bunyaviridae Infections / immunology*
  • Bunyaviridae Infections / virology
  • Cell Line
  • China
  • Chlorocebus aethiops
  • Cross Reactions / immunology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Neutralization Tests / methods*
  • Phlebovirus / genetics
  • Phlebovirus / immunology*
  • Phlebovirus / physiology
  • Phylogeny
  • Quality Control
  • Rabbits
  • Reference Standards
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Vero Cells
  • Viral Envelope Proteins / classification
  • Viral Envelope Proteins / genetics
  • Viral Vaccines / immunology*
  • Viral Vaccines / standards

Substances

  • Viral Envelope Proteins
  • Viral Vaccines