# Serial Cell-Culture Passage of Severe Fever with Thrombocytopenia Syndrome Virus Attenuates Virulence and Confers Protective Immunity in Mice

## TL;DR

Researchers developed a weakened version of the SFTSV virus through cell culture passage, which protected mice from lethal infection and could serve as a vaccine candidate.

## Contribution

A novel live-attenuated SFTSV vaccine candidate was developed and shown to confer cross-protective immunity in mice.

## Key findings

- Attenuated SFTSV strains showed reduced virulence and viral loads in mice.
- The vaccine induced strong antibody and cellular immune responses.
- It provided complete protection against lethal challenge with different SFTSV genotypes.

## Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease with high case–fatality rates in East Asia, yet no licensed vaccines are currently available. Here, we generated attenuated severe fever with thrombocytopenia syndrome virus (SFTSV) strains through serial passage in Huh-7 cells and evaluated their pathogenicity, immunogenicity, and protective efficacy. Attenuation candidates were selected based on reduced pathogenicity, estimated based on the median lethal dose (LD50), and genetic sequencing was performed to identify mutations associated with attenuation. In C57BL/6 IFNAR−/− mice, the attenuated strain exhibited markedly reduced virulence and viral loads while inducing robust virus-specific IgG, neutralizing antibody, and cellular immune responses. Notably, immunization with the attenuated strain conferred complete protection against lethal challenge with heterologous SFTSV genotypes. Genomic analysis revealed nonsynonymous mutations in the RNA-dependent RNA polymerase (RdRp), glycoprotein, and NSs genes, implicating alterations in viral replication, entry, and immune evasion. Collectively, these findings demonstrate that serial cell-culture passage can generate attenuated SFTSV strains that retain strong immunogenicity and cross-protective efficacy, supporting their potential as live-attenuated vaccine candidates for SFTS.