A hTfR1 Receptor-Specific VHH Antibody Neutralizes Pseudoviruses Expressing Glycoproteins from Junín and Machupo Viruses

• Published in: Viruses 2024-12, Vol.16 (12), p.1951
• Main Authors: Kang, Qinglin, Li, Gege, Wu, Yan, Wang, Shaoyan, Chen, Zhengshan, Zai, Xiaodong, Pan, Xiaoyan, Wang, Rong, Lu, Jiansheng, Du, Peng, Yang, Zhixin, Chi, Xiangyang, Xiao, Gengfu, Xu, Junjie
• Format: Article
• Language: English
• Subjects: Adjuvants; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, CD - metabolism; Arenaviruses; Arenaviruses, New World - genetics; Arenaviruses, New World - immunology; Camelids; Epitopes; Epitopes - immunology; Fever; Glycoproteins; Glycoproteins - genetics; Glycoproteins - immunology; Glycoproteins - metabolism; Health aspects; HEK293 Cells; Hemorrhagic fever; HIV; Human immunodeficiency virus; Humans; Immunization; Infections; Infectious diseases; Junin virus - genetics; Junin virus - immunology; Junín viruses; Libraries; Machupo viruses; Medical research; Pathogenesis; Physiological aspects; Plasma; R&D; Receptors, Transferrin - immunology; Receptors, Transferrin - metabolism; Receptors, Virus - immunology; Receptors, Virus - metabolism; Research & development; Single-Domain Antibodies - genetics; Single-Domain Antibodies - immunology; Single-Domain Antibodies - metabolism; Stomatitis; transferrin receptor 1; Vaccines; VHH antibody; Viral antibodies; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Envelope Proteins - metabolism; Viral infections; Virus Internalization; Viruses
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v16121951

The Junín virus (JUNV) is one of the New World arenaviruses that cause severe hemorrhagic fever. Human transferrin receptor 1 (hTfR1) has been identified as the main receptor for JUNV for virus entry into host cells. To date, no treatment has been approved for JUNV. Herein, we investigated 12 anti-hTfR1 VHH (variable domain of the heavy chain of heavy-chain antibody) antibodies and confirmed their interaction with hTfR1. Most of them could bind to the hTfR1 apical domain, which is the glycoprotein 1 (GP1) binding domain of JUNV. Among them, 18N18 exhibited neutralizing activity against both the human immunodeficiency virus (HIV)-vectored lentiviral Junín pseudoviruses and the recombinant vesicular stomatitis virus (VSV)-vectored Junín pseudoviruses. We also verified that 18N18 blocked the interaction between hTfR1 and JUNV GP1. In addition, 18N18 could neutralize another New World arenavirus, the Machupo virus. Using AlphaFold 3-based simulation of 18N18-hTfR1 docking, we determined that 18N18's binding epitope was located at the JUNV GP1 binding epitope. 18N18 represents a candidate for JUNV treatment and provides a potential approach that could be applied to New World arenaviruses.