Science: Detailed explanation of our scientists have developed a SARS-CoV-2 strain adapted to mice that can be used to test vaccine efficacy.

!--:page title"----- the 2019 coronavirus pandemic caused by the new SARS-CoV-2 has become a global health crisis.
SARS-CoV-2 has shown unprecedented human-to-human transmission in the absence of protective immunity to all humans.
Although several candidate vaccines are currently undergoing clinical trials, there is currently no commercialIZED COVID-19 vaccine.
SARS-CoV-2 and two other highly pathogenic viruses closely related to SARS-CoV and MERS-CoV belong to the co-genus of the coronavirus family.
SARS-CoV-2 has a 30kb size of a justice, single-stranded RNA genome.
its nucleoshell protein (N) and an outer membrane consisting of membrane protein (M), endomesine protein (E) and a hedgehog protein (S) are encased in its genome.
, like SARS-CoV, the SARS-CoV-2 S protein binds to their common receptor angiotensin conversion enzyme 2 (ACE2) through a receptor binding domain (RBD) to mediate the virus into the host cell.
before, scientists have confirmed that THE RBD of SARS-CoV and MERS-CoV contain the main conformational dependence neutraland epithelial, and are able to cause strong neutralizing antibodies in immune animals, making it a promising target for vaccine development.
there is an urgent need to develop small animal models that reproduce SARS-CoV-2 infection.
Given that SARS-CoV-2 does not use mice ACE2 as its receptor, wild mice are considered less susceptible to SARS-CoV-2 infection.
have developed genetically modified mice that express human ACE2 through different strategies.
such mice have previously been used to study SARS-CoV-2 infection and pathogenesis and to evaluate coping strategies for COVID-19. In a new study
, Shihui Sun, Cheng-Feng Qin and Yusen Zhou, the late, and Shibo Jiang of Fudan University's Institute of Pathogen Microbiology developed a SARS-CoV-2 strain adapted to mice that can replicate efficiently in the respiratory tract and cause interstitial pneumonia in immune-active wild types. In addition, they tested the protective effect of a newly developed recombinant subunit candidate vaccine in a mouse model that challenged the SARS-CoV-2 strain.

related findings were published online July 30, 2020 in the journal Science, under the title "Right of SARS-CoV-2 in BALB/mice for testing vaccineacy".
picture from Pixabay/CC0 Public Domain.
In stead at the new study, instead of genetically modifying mice to express human ACE2, the researchers took a new strategy: They improved a clinically observed strain of SARS-CoV-2 to adapt to the respiratory tract of mice.
the SARS-CoV-2 mutation they built, called MASCp6, which can be replicated in both young and elderly mice, and both groups developed pneumonia and inflammatory reactions after being infected with maSCp6 in the nose, a clinical feature observed in human patients.
the researchers, deep sequencing of the MASCp6 genome compared to SARS-CoV-2 showed that mutations in the receptor-binding domain (RBD) of the virus's stingprotein may have contributed to MASCp6's ability to enter mice with ACE2-positive cells.
to show the usefulness of their new model in testing the candidate vaccine, the researchers immunized female mice with two doses of recombinant subunit candidate vaccine and then infected them with MASCp6 virus.
they found that the vaccinated mice had a lower viral load and found no significant clinical symptoms compared to the unvaccinated control group mice.
the SARS-CoV-2 strain developed by these researchers in mice and the corresponding mouse infection model increased the number of animal models studied for SARS-CoV-2 transmission.
this is important because there is currently no animal model infected with SARS-CoV-2 that reproduces all aspects of human disease.
an ideal COVID-19 animal model should re-emphasis on viral replication and clinical outcomes observed in patients with COVID-19.
in this study, the researchers reported the rapid adaptability of SARS-CoV-2 in BALB/c mice, producing MASCp6 strains that not only replicate efficiently in the trachea and lungs, but also cause interstitial pneumonia and inflammatory reactions, reproducing many of the clinical features observed in patients with COVID-19.
after MASCp6 vaccination, SARS-CoV-2 was mainly replicated in the respiratory tract of mice, and the viral RNA in the lungs peaked after 3 days of vaccination, then declined after 5 and 7 days of inoculation.
these results are consistent with other genetically modified mice or humanized mouse models.
of particular note is that older mice experienced more severe lung damage after MASCp6 vaccination than young mice, reflecting the fact that COVID-19 mortality and fatality rates were strongly biased in favour of older people.
mortality rate was only reported by Jiang et al. in ACE2 genetically modified mice infected with SARS-CoV-2 (Cell, 2020, doi: 10.1016/j.cell.2020.05.027).
in the SARS-CoV and MERS-CoV studies, a challenging model based on adaptive strains in mice has been developed.
virus in the continuous transmission of the virus in the lungs of mice lead to adaptive mutations, which increase the ability of viral infections.
MASCp6 genome contains five mutations, which cause changes in the four amino acid residues of the ORF1ab, S and N genes, compared with its parent strain IME-BJ05.
N501Y mutation appears to make the viral protrusion protein and mouse ACE2 more beneficial interaction, allowing it to attach and enter the mouse host cell, resulting in an increase in the virulation phenotype of the mouse.
In addition to N501Y, whether the other three amino acid changes also regulate viral infection is still to be determined.
further reverse genetics research will solve this problem and may also allow people to quickly synthesize recombinant SARS-CoV-2 with enhanced toxicity.
in addition, immunostaining results showed that lung rod cells and AT2 cells were the main target cells of MASCp6, in line with previous studies from animal models and PATIENTs with COVID-19.
!--/ewebeditor:!--webeditor: "page title" - compared to the previously described ACE2 genetically modified mice or humanized mice, the researchers developed a challenge model based on MASCp6 using immune-capable wild-type mice and applied them directly to the evaluation of the efficacy of various candidate vaccines.
immunize these mice with recombinant subunit candidate vaccine (RBD-Fc) to induce high levels (up to 1:320) of anti-SARS-CoV-2 neutralizing antibodies, virtually eliminating viral RNA replication in the lungs of mice after being challenged by MASCp6.
the potential correlation between serum and antibody titer and protective efficacy in vaccinated mice, highlighting the versatility of this convenient and economical animal model.
recently, non-human primates closest to humans on the system evolution tree have also been used to reproduce SARS-CoV-2 infection, and several candidate vaccines have been proven in them for good protection.
hamsters, ferrets and cats are also susceptible to SARS-CoV-2, and clinical outcomes after SARS-CoV-2 infection range from asymptomatic infection to severe pathological lung lesions.
there is currently no animal model of SARS-CoV-2 infection that reproduces all aspects of human disease.
therefore, the establishment of different animal models should greatly expand our understanding of SARS-CoV-2 transmission and pathogenesis, and accelerate the development of COVID-19 correspondence strategy.
(bioon.com) References: 1. Hongjing Gu et al. The Right of SARS-CoV-2 in BALB/c mice for testing effic. Science, 2020, doi: 10.1126/science.abc4730. a SARS-CoV-2 mouse model to study viral and candidates.