An ultrapotent neutralizing antibody protected non-human primates from severe fever with thrombocytopenia syndrome virus infection 2895

Abstract Description Background Severe fever with thrombocytopenia syndrome virus (SFTSV) is tick-borne bunyavirus with a fatality rate up to 30%, posing a severe public health threat. There is currently no therapeutics for SFTSV infection. Results Here, from SFTSV convalescent donors, we discovered an ultrapotent NAb ZS004-1C5 with subnanomolar neutralization titers (IC50=0.3 ng/mL). Cyro-EM structure revealed that ZS004-1C5 has a super long HCDR3 (23aa) to reach a unique “groove epitope” on SFTSV Gn. Next, mouse protection studies demonstrated that delayed (up to 48 hrs) therapeutic treatment of ZS004-1C5 100% protected STAT1-/- mice from lethal SFTSV challenge. In a non-human primate model, therapeutic administration of ZS004-1C5 significantly protected rhesus macaques from SFTSV-induced synptoms, viremia and inflammation. Lastly, using AI-guided algorithms, we identified ZS004-1C5-like NAbs from human BCR repertoire and discovered a germline IgM that can neutralize SFTSV. Our study is the first antibody protection study against SFTSV in monkeys. Conclusion Our findings provided proof-of-concept data to support clinical development of this antibody for SFTSV therapy, and discovered a novel neutralizing epitope that could benefit future vaccine design works. Funding Sources This work was supported by the Education Foundation of Westlake University and the HRHI program of Westlake Laboratory of Life Sciences and Biomedicine 1010060220B1. Topic Categories Vaccines and Immunotherapy (VAC)