Potent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains

• DOI: 10.1038/s41467-024-47213-8
• Publication Date: 2024-04-06T14:01:59Z
• Authors: Li Chen; Mengmeng Sun; Huajun Zhang; Xinghai Zhang; Yanfeng Yao; Ming Li; Kangyin Li; Pengfei Fan; Haiwei Zhang; Ye Qin; Zhe Zhang; Entao Li; Zhen Chen; Wuxiang Guan; Shanshan Li; Changming Yu; Kaiming Zhang; Rui Gong; Sandra Chiu
• Keywords: Hendra Virus

Abstract Nipah virus (NiV) is a World Health Organization priority pathogen and there are currently no approved drugs for clinical immunotherapy. Through the use of naïve human phage-displayed Fab library, two neutralizing antibodies (NiV41 NiV42) targeting NiV receptor binding protein (RBP) were identified. Following affinity maturation, derived from NiV41 display cross-reactivity against both Hendra (HeV), whereas antibody based on NiV42 only specific to NiV. Results immunogenetic analysis reveal correlation between maturation their antiviral activity. In vivo testing its mature form (41-6) show protective efficacy lethal challenge in hamsters. Furthermore, 2.88 Å Cryo-EM structure tetrameric RBP complex demonstrates that 41-6 blocks interface. These findings can be beneficial development design vaccines with broad spectrum henipaviruses.