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Literature detail

Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy.

Hongjing Gu1 Qi Chen1 Guan Yang2 Lei He1 Hang Fan1 Yong-Qiang Deng1 Yanxiao Wang2 Yue Teng1 Zhongpeng Zhao1 Yujun Cui1 Yuchang Li1 Xiao-Feng Li1 Jiangfan Li1 Na-Na Zhang1 Xiaolan Yang1 Shaolong Chen1 Yan Guo1 Guangyu Zhao1 Xiliang Wang1 De-Yan Luo1 Hui Wang1 Xiao Yang2 Yan Li3 Gencheng Han3 Yuxian He4 Xiaojun Zhou5 Shusheng Geng6 Xiaoli Sheng6 Shibo Jiang7 Shihui Sun8 Cheng-Feng Qin8 Yusen Zhou1
Affiliations 8 institutions
  1. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
  2. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
  3. Institute of Military Cognition and Brain Sciences, Beijing 100850, China.
  4. Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
  5. Laboratory Animal Center, Academy of Military Medical Sciences, Beijing 100071, China.
  6. Beijing JOINN Biologics Co., Beijing 100176, China.
  7. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. [email protected] [email protected] [email protected].
  8. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China. [email protected] [email protected] [email protected].
PMID 32732280 2020 Science eng ppublish
PubMed DOI Browse context

Article

Publication summary

The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.

Disease Models, Animal Mice Administration, Intranasal Angiotensin-Converting Enzyme 2 Animals Betacoronavirus Coronavirus Infections COVID-19 COVID-19 Vaccines Female High-Throughput Nucleotide Sequencing Humans Immunogenicity, Vaccine Lung Lung Diseases, Interstitial Mice, Inbred BALB C Mice, Transgenic Mutation

Structured evidence records

Evidence records

3 total
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.95
Key finding

SARS-CoV-2 was experimentally adapted to infect and replicate in BALB/c mice, producing a mouse-adapted strain (MASCp6) that caused pneumonia upon intranasal inoculation.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation.

Method
serial passaging; experimental infection; intranasal inoculation
Sample type
respiratory tract; lung
Experimental system
in vivo animal experiment
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 1.00
Key finding

The mouse-adapted SARS-CoV-2 strain MASCp6 acquired the N501Y mutation in the spike receptor binding domain, associated with increased virulence in mice.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein.

Genes or proteins
spike
Mutations
N501Y
Mechanism types
receptor_binding; pathogenicity
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.80
Key finding

Mouse-adapted SARS-CoV-2 acquired N501Y in the spike receptor-binding domain, indicating adaptation affecting ACE2 receptor usage and facilitating infection in BALB/c mice.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein.

Method
deep sequencing
Receptors
Angiotensin-Converting Enzyme 2