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Mol. Ther., October 23, 2025 | https://doi.org/10.1016/j.ymthe.2025.10.044 Recombinant Dabie Bandavirus as an effective bivalent vaccine platform inducing protective immunity against intracellular pathogen and cancer

Hyo‐Jin Ro^1,2,† ∙ Yebeen Lee^1,2,^† ∙ Kyeongseok Jeon^1,2 ∙ Yujin Kim³ ∙ Seung Ho Baek³ ∙ Green Kim³ ∙ Joowan Kim^1,2 ∙ Jun‐Gu Kang⁴ ∙ Na-Yoon Jang^1,2,5 ∙ Si-Hyeon Lee^1,2∙ Sun-Young Kim^1,2 ∙ Yu-Jin Kim^1,2,5 ∙ Na-Young Ha⁶ ∙ Yuri Kim⁷ ∙ Young Ki Choi⁸∙ Jae U. Jung⁹ ∙ Jung Joo Hong^3,10 ∙ Nam‐Hyuk Cho^1,2,5,11

¹Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea

²Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea

³National Primate Research Centre, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Chungcheongbuk-do 28116, Republic of Korea

⁴Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea

⁵Institute of Endemic Disease, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea

⁶Translational immunology institute, Chungnam National University, Daejeon 35015, Republic of Korea

⁷Department of Microbiology, Soon Chun Hyang University College of Medicine, Cheonan, Chungcheongnam-do 33151, Republic of Korea

⁸Center for Study of Emerging and Re-emerging Viruses, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, South Korea

⁹Department of Infection Biology, Global Center for Pathogen and Human Health Research, Cleveland Clinic, Ohio 44195, USA

¹⁰KRIBB School of Bioscience, Korea University of Science & Technology (UST), Daejeon 34141, Republic of Korea

¹¹Seoul National University Bundang Hospital, Seongnam, Gyeonggi‐do 13620 Republic of Korea

†These authors contributed equally to this work.

Corresponding author Nam-Hyuk Cho

Abstract

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 virus, which lacks the nonstructural (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 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

논문정보

형식Research article
게재일2025년 10월 (BRIC 등록일 2025-10-27)
연구진국내(교신)+국외 연구진
분야 의약학 > 감염의학

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