Cattle and human organoids reveal 2.3.4.4b H5N1 cross-species transmission potential and neuraminidase-specific neutralizing antibodies in humans
Abstract
Abstract The unexpected circulation of clade 2.3.4.4b H5N1 influenza viruses in dairy cattle and the transmission to diverse mammalian species poses a pandemic risk. We sought to explore cattle and human respiratory susceptibility to the 2.3.4.4b H5N1 virus. We establish long-term expandable cattle airway and mammary organoids. The 2.3.4.4b H5N1 virus exhibits high replicative fitness in cattle mammary organoids, recapitulating its remarkable mammary tropism. The virus also replicates robustly in cattle airway organoids, suggesting an underrecognized respiratory component in ongoing outbreaks. Interestingly, human airway and nasal organoids are highly susceptible to the 2.3.4.4b H5N1 virus. Yet, a novel organoid-based neutralization assay reveals that N1 antibodies in human sera had cross-neutralizing activity against the 2.3.4.4b H5N1 and ancestral H5N1-VN1194 viruses. The cross-neutralization, exclusively manifested in the organoid-based assay, is enhanced after seasonal influenza vaccination and diminished after depleting N1-specific antibodies. Therefore, cross-neutralizing N1 antibodies are likely limiting zoonotic infection by H5N1 viruses in humans.
Article Details
Authors (31)
Cun Li
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Yifei Yu
Zhixin Wan
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Jian-Piao Cai
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Jingjing Huang
College of Life Sciences, South China Agricultural University
Xiaoxin Zhu
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Jiali Wu
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Wei Xue
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Engineering Technology Research Center of Drug Carrier of Guangdong, Department of Biomedical Engineering
Ying Zhou
Man Chun Chiu
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Qiaoshuai Lan
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Shuxin Zhang
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Zijun Zhao
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Yidong Yang
Yuhong Liu
State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter and College of Chemistry
Pui Wang
Shaofeng Deng
Ming Yue
Longchao Zhu
Keshan Zhang
Mengmeng Zhao
Jieshi Yu
Wenkang Wei
Xiang Gao
Lin Huang
Hin Chu
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Gang Wu
Honglin Chen
Department of Mechanical and Energy Engineering
Kwok Yung Yuen
Richard Webby
Jie Zhou