United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
Division of Biomedical Sciences, University of California Riverside, Riverside, CA, USA.
Nat Commun. 2024 Feb 26;15(1):1722. doi: 10.1038/s41467-024-46110-4.
Crimean-Congo hemorrhagic fever virus (CCHFV) is a WHO priority pathogen. Antibody-based medical countermeasures offer an important strategy to mitigate severe disease caused by CCHFV. Most efforts have focused on targeting the viral glycoproteins. However, glycoproteins are poorly conserved among viral strains. The CCHFV nucleocapsid protein (NP) is highly conserved between CCHFV strains. Here, we investigate the protective efficacy of a CCHFV monoclonal antibody targeting the NP. We find that an anti-NP monoclonal antibody (mAb-9D5) protected female mice against lethal CCHFV infection or resulted in a significant delay in mean time-to-death in mice that succumbed to disease compared to isotype control animals. Antibody protection is independent of Fc-receptor functionality and complement activity. The antibody bound NP from several CCHFV strains and exhibited robust cross-protection against the heterologous CCHFV strain Afg09-2990. Our work demonstrates that the NP is a viable target for antibody-based therapeutics, providing another direction for developing immunotherapeutics against CCHFV.
克里米亚-刚果出血热病毒（CCHFV）是世界卫生组织的优先病原体。基于抗体的医疗对策提供了减轻 CCHFV 引起的严重疾病的重要策略。大多数努力都集中在针对病毒糖蛋白上。然而，糖蛋白在病毒株之间的保守性较差。CCHFV 的核衣壳蛋白（NP）在 CCHFV 株之间高度保守。在这里，我们研究了针对 NP 的 CCHFV 单克隆抗体的保护效力。我们发现，针对 NP 的单克隆抗体（mAb-9D5）可保护雌性小鼠免受致死性 CCHFV 感染，或与同种型对照动物相比，导致患病小鼠的平均死亡时间显著延迟。抗体的保护作用独立于 Fc 受体功能和补体活性。该抗体结合了来自几种 CCHFV 株的 NP，并对异源 CCHFV 株 Afg09-2990 表现出强大的交叉保护作用。我们的工作表明，NP 是抗体治疗的可行靶标，为开发针对 CCHFV 的免疫疗法提供了另一个方向。
