Recombinant Dabie bandavirus as a bivalent vaccine platform inducing protective immunity against intracellular pathogens and cancer.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen endemic to East Asia, associated with high mortality and lacking approved vaccines or therapies. We developed a live-attenuated vaccine platform based on a recombinant SFTSV, which lacks the nonstructural protein on the S segment (NSs) gene, a key virulence factor that suppresses type I interferon responses. The resulting ΔNSs viruses, reassorted with the prevalent genotype B, showed attenuated replication in interferon-competent cells while retaining the ability to infect and activate antigen-presenting cells (APCs). Immunization with the ΔNSs virus elicited robust SFTSV-specific humoral and cellular immune responses in mice and non-human primates, conferring complete protection against lethal challenge across multiple SFTSV genotypes, with immunity lasting up to 12 months. Additionally, recombinant ΔNSs viruses encoding heterologous antigens, such as ovalbumin (OVA) or type-specific antigen 56 (TSA56) from Orientia tsutsugamushi, induced strong antigen-specific T cell responses and conferred protection against OVA-expressing melanoma or scrub typhus, respectively. Mechanistically, ΔNSs viruses enhanced APC activation, improved antigen presentation, and reduced apoptosis in infected cells, supporting effective T cell priming. These findings establish SFTSV ΔNSs as an immunogenic and broadly protective vaccine candidate and a versatile bivalent vector platform for targeting viral, intracellular bacterial, and tumor-associated antigens.