A rabies virus vectored severe fever with thrombocytopenia syndrome (SFTS) bivalent candidate vaccine confers protective immune responses in mice

Abstract The Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic zoonotic disease, which is potentially fatal in human with mortality rates ranging from 16.2% to 32%. The rabies virus (RABV) LBNSE vector expressing foreign antigens have shown considerable promise as vaccines against viral diseases, which is effective and safe. In the present study, we generated a recombinant RABV rLBNSE-Gn expressing a SFTSV glycoprotein Gn by reverse genetic technology to control rabies and SFTS in animals. An extra insertion of Gn gene did not impact replication of the recombinant virus rLBNSE-Gn in NA and BHK-21 cells compared to the parent rLBNSE strain. The SFTSV Gn gene together with RABV N and G genes were efficiently expressed in rLBNSE-infected Vero cells by immunostaining and immune blots. A single dose of 107 FFU of the rLBNSE-Gn intramuscularly inoculated in BALB/c mice induced rapid and robust humoral responses against both RABV and SFTSV without any signs of disease or weight loss. Compared to the rLBNSE and DMEM groups, the extra Gn expression contributed to the recruitments and/or activations of the dendritic cells and B cells from inguinal lymph nodes of BALB/c mice vaccinated with rLBNSE-Gn. The protective efficacy of rLBNSE-Gn against SFTSV in C57BL/6 mice was evaluated, and the virus loading in the spleens reduced to 10 TCID50/mg at 7 days post SFTSV infections, which indicated that the rLBNSE-Gn conferred efficacious protective immune responses from SFTSV in C57BL/6 mice. All the mice immunization with rLBNSE-Gn and rLBNSE survived after a lethal RABV challenge, suggesting a 100% protection from RABV. Therefore, the rLBNSE-Gn would be a promising bivalent candidate vaccine against SFTS and rabies in animals.