Coronavirus for mice
Chinese biologists have created a new strain of SARS-CoV-2 coronavirus capable of infecting rodents
Maria Azarova, Naked Science
A group of scientists from the Beijing Institute of Microbiology and Epidemiology has created a new strain of SARS-CoV-2 coronavirus (the causative agent of Covid-19 infection), which is able to effectively infect laboratory mice. As explained in a study published on the bioRxiv preprint website (Gu et al., Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy), the new version of SARS-CoV-2 will help to speed up the testing of vaccines easily and cheaply, which hundreds of scientists are currently working on to the whole world.
"To develop safe and effective vaccines, suitable animal-tested models should be created. We report on the rapid adaptation of SARS-CoV-2 in mice of the BALB/c inbred line (one of the most popular genetic lines of laboratory mice is albino and immunodeficient. – Ed.), on the basis of which a convenient, economical and effective system for testing [vaccines] on animals was developed. In particular, we found that the MACSp6 strain adapted to mice effectively infected both elderly and young individuals, which led to the development of moderate pneumonia in them, as well as inflammatory reactions," the biologists write.
Earlier studies, the scientists explain, have shown the possibility of breeding transgenic mice with the human ACE2 receptor and thus able to become infected with coronavirus, but on an "industrial scale" it takes a lot of time. In addition, the disease in the body of such rodents proceeds in an extremely weakened form: inflammatory reactions are weak, as well as lung damage. However, the new work found that ordinary laboratory mice infected with a new strain of MASCp6 showed acute and moderate inflammatory reactions with infiltration of macrophages in the lungs and an increased content of some inflammatory cytokines.
"Small model animals, such as mice, provide reliable and convenient approaches for in vivo evaluation of the effectiveness of antiviral countermeasures, including vaccines and preventive/therapeutic agents. However, ordinary mice, as a rule, are not susceptible to infection with human coronaviruses using their proteins as receptors. For example, MERS-CoV (the causative agent of the Middle East respiratory syndrome. – Ed.) It does not infect wild mice, but infects rodents expressing the membrane enzyme dipeptidyl peptidase-4 (DPP4). <...> At the same time, a small number of transgenic mice capable of contracting SARS-CoV-2, as well as associated costs, including maintenance, seriously hampered the development of a vaccine against Covid-19," the authors add.
The increased infectivity of MACSp6 – the property of a parasitic microorganism to survive in the host body – in mice participating in the study was explained by the replacement of a key residue (N501Y) in the receptor-binding domain (RBD) of S-protein, which covers the envelope of the viral particle (earlier another group of scientists found out that the RBD domain of viral proteins SARS-CoV-2 evolved so as to interact as effectively as possible with ACE2 on the surface of host cells). Thus, the coronavirus variation acquired the ability to infect laboratory animals in just six transitions between their generations.
Then, Chinese biologists, using their new model on laboratory animals, in vivo evaluated the effectiveness of an experimental subunit vaccine (an immunogenic drug that is chemical components that are removed from the structure of a microbial cell or virus; subunit vaccines may include nucleic acids (DNA or RNA) isolated from the structure of a microbial cell, ribosomes, proteins, lipopolysaccharides, glucidolipoprotein complexes) based on the RBD domain.
The results of the experiment showed that the drug caused potent neutralizing antibodies and provided full protection against infection with the MACSp6 version without detectable viral RNA in the lungs and trachea. As the biologists emphasized, their vaccine "based on RBD has great prospects for further development and prevention of the Covid-19 pandemic." However, it is worth recalling that this work has yet to be reviewed, so it is too early to draw far-reaching conclusions.
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