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A rationally designed cocktail of nanobodies elicited by heterologous vaccination confers protection against SFTSV in preclinical models
Wu, XL; Zhu, LJ; Liang, SJ; Chang, Z; Wang, YX; Zou, QC; Xu, ZL; Zhang, DD; Hu, JQ; Geng, SY; Li, ZF; Yu, WK; Hu, ZL; Chen, M; Cao, K; Jia, B; Wei, HX; Cai, RT; Long, JY; Yang, XM; Yang, QJ; Yu, ZJ; Shi, LE; Xu, BH; Zheng, YW; Meng, SR; Cai, JM; Zhou, GF; Zhu, KR; Dou, YB; Lou, ZY; Li, MH; Wu, Y; Wu, ZW
2025
发表期刊Sci. Transl. Med.
ISSN1946-6234
卷号17期号:825
摘要Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne phlebovirus, poses a growing public health threat, with no approved vaccines or targeted therapies. Its genetic diversity and rapid reassortment have hindered the development of broadly effective interventions. Here, we isolated and characterized broadly neutralizing camelid nanobodies generated by a heterologous immunization strategy. These nanobodies exhibited cross-subtype neutralization and conferred protection against disease in humanized and lethal murine models of SFTSV infection. Structural analysis revealed binding to distinct, nonoverlapping epitopes on the viral glycoprotein complex. A rationally designed cocktail leveraging this epitope diversity achieved complete viral inhibition through synergistic mechanisms. In both murine and immunocompetent ferret models, the cocktail enabled efficient viral clearance and full protection against lethal challenge. These results demonstrate the therapeutic potential of nanobody cocktails for SFTSV infection and establish a generalizable framework for nanobody-based countermeasures against genetically variable emerging viruses, including other members of the Bunyavirales order.
收录类别SCIE
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/15212
专题其他
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GB/T 7714
Wu, XL,Zhu, LJ,Liang, SJ,et al. A rationally designed cocktail of nanobodies elicited by heterologous vaccination confers protection against SFTSV in preclinical models[J]. Sci. Transl. Med.,2025,17(825).
APA Wu, XL.,Zhu, LJ.,Liang, SJ.,Chang, Z.,Wang, YX.,...&Wu, ZW.(2025).A rationally designed cocktail of nanobodies elicited by heterologous vaccination confers protection against SFTSV in preclinical models.Sci. Transl. Med.,17(825).
MLA Wu, XL,et al."A rationally designed cocktail of nanobodies elicited by heterologous vaccination confers protection against SFTSV in preclinical models".Sci. Transl. Med. 17.825(2025).
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