Mouse-Adapted SARS-CoV-2 Strain and RBD Subunit Vaccine Evaluation

Jul 7, 2026

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The work addresses the need for small-animal models that recapitulate SARS-CoV-2 infection and enable rapid assessment of countermeasures. It reports generation of a mouse-adapted SARS-CoV-2 strain capable of replicating in wild-type immunocompetent mice and producing interstitial pneumonia. The study also evaluates the protective efficacy of a newly developed recombinant subunit vaccine candidate based on SARS-CoV-2 RBD using the mouse challenge model. Key infection dynamics and target lung cells are analyzed.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages5

Reading Time13 min

Results

Rapid adaption of SARS-CoV-2 in BALB/c mice

Characterization of MASCp6 infection in BALB/c mice

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

RESEARCH CORONAVIRUS SARS-CoV-2, and the lung tissues were col- T he pandemic of coronavirus disease 2019 (COVID-19) caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health crisis (1–3) . In the ab- sence of protective immunity in the whole human population (4), SARS-CoV-2 has exhibitedan unprecedented human-to-human transmission capability. Although several vaccine candidates are being currently tested in clinical trials, no commercial COVID-19 vaccine is presently available. SARS-CoV-2 belongs to the Betacoronavirus genus of the Coronaviridae family, along with two other closely related highly pathogenic viruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) . SARSCoV-2 has a positive-sense, single-stranded RNAgenome of30 kbin length, which is coated by the inner nucleocapsid (N) proteins and an outer envelope made up of membrane(M) and envelope (E) proteins, as well as spike (S) proteins. Like SARS-CoV, the S protein of SARSCoV-2 mediates viral entry into host cells by binding to their shared receptor, angiotensin- 1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China. 2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. 3Institute of Military Cognition and Brain Sciences, Beijing 100850, China. 4Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. 5Laboratory Animal Center, Academy of Military Medical Sciences, Beijing 100071, China. 6Beijing JOINN Biologics Co. , Beijing 100176, China. 7Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. *These authors contributed equally to this work. †Corresponding author. Email: [shibojiang@fudan.edu.cn](shibojiang@fudan.edu.cn) (S.J.); [sunsh01@163.com](sunsh01@163.com) (S.S.); [qincf@bmi.ac.cn](qincf@bmi.ac.cn) (C.-F.Q.) ‡These authors contributed equally to this work. §Deceased. converting enzyme 2 (ACE2), through the receptor-binding domain (RBD) (1). Previously, we and others have demonstrated that the RBD of SARS-CoV and MERS-CoV contain major conformation-dependent neutralizing epitopes and are capable of eliciting potent neutralizing antibodies in immunized animals, thus representing promising targets for vaccine development (5–8). Small-animal models that recapitulate SARSCoV-2 infection are urgently needed. Because SARS-CoV-2 does not use mouse ACE2 as its receptor (1), wild-type mice are thought tobe less susceptible to SARS-CoV-2 . Transgenic mice expressing human ACE2 have been developed by means of different strategies. Such mice have been used previously to study SARSCoV-2 infection and pathogenesis and to evaluate countermeasures against COVID-19 (9–11). Here, we report the generation of a mouseadapted strain of SARS-CoV-2 that can productively replicate in the respiratory tract and cause interstitial pneumonia in wild-type immunocompetent mice. Additionally, the protective efficacy of a newly developed recombinant subunit vaccine candidate based on SARSCoV-2 RBD was assayed by using this mouse challenge model. Results Rapid adaption of SARS-CoV-2 in BALB/c mice To generate a SARS-CoV-2 mouse-adapted strain, the human clinical isolate of SARSCoV-2 (BetaCov/human/CHN/Beijing_IMEBJ05/2020, abbreviated as IME-BJ05) was serially passaged by means of intranasal inoculation in aged mice (Fig. 1A), as previously described for SARS-CoV (12). Briefly, 9-monthold BALB/c mice were intranasally inoculated with 7.2 × 105 plaque forming units (PFU) of 1C), with peak viral RNA loads of ~1010 copies/ g at 3 days after inoculation, which was comparable with the results from the human ACE2 transgenic

FAQs

Why is a small-animal model for SARS-CoV-2 infection urgently needed?

Because SARS-CoV-2 infection needs models that reproduce key aspects of disease and allow evaluation of countermeasures, while conventional mouse susceptibility is limited due to receptor differences.

How was the mouse-adapted SARS-CoV-2 strain generated?

A human clinical isolate was serially passaged in aged mice through intranasal inoculation until adaptation enabled productive replication in the respiratory tract.

Which vaccine strategy was tested in the mouse challenge model?

A recombinant subunit vaccine candidate based on the SARS-CoV-2 receptor-binding domain (RBD), with protective efficacy assessed using the adapted-virus challenge system.

Jul 7, 2026

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