The study sheds light on a recombinant vaccine against SARS-CoV-2 in mice

Researchers can further modify the vaccination vaccine, the modified vaccine virus Ankara (MVA), into a recombinant form to express the SARS-CoV-2 virus peplomer, once or twice with recombinant MVA. I found that I was protected by the injection of. Transgenic mice from lethal infections. Vaccination also prevents the detection of infectious SARS-CoV-2 in the lungs of mice.

The authors of this study were Ruikang Liu, Jeffrey L. Americo, Catherine A. Cotter, Patricia L. Earl, Noam Erez, Chen Peng and others. The results of this study were published in the journal PNAS.

Vaccines are needed to control Covid-19 during, and perhaps after, the current pandemic. Recombinant nucleic acids, proteins, and viral vectors that stimulate the immune response to the SARS-CoV-2 S protein provided protection in laboratory animal and human clinical trials, but with respect to their ability to prevent spread and duration of immunity. The question remains.

This study focuses on the replication-restricted modified vaccinia virus ancara (MVA), which has been shown to be a safe, immunogenic, stable smallpox vaccine and a promising vaccine vector for other infectious diseases and cancers. I’m guessing. In a transgenic mouse model, one or two injections of recombinant MVA expressing a modified form of S inhibit SARS-CoV-2 replication in the upper and lower respiratory tracts and prevent serious disease. I did.

Modified vaccinia virus Ankara (MVA) is a replication-restricted smallpox vaccine, and numerous clinical studies of recombinant MVA (rMVA) as a vector for the prevention of other infectious diseases, including Covid-19, are underway.

Here, researchers characterize rMVA, which expresses the S protein of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Individual or combination changes to full-length S included two proline substitutions, a mutation in the furin recognition site, and deletion of the endoplasmic reticulum search signal.

Another rMVA was also constructed in which the receptor binding domain (RBD) is adjacent to the signal peptide and the transmembrane domain of S. Each modified S protein appeared on the surface of rMVA-infected cells and was recognized by anti-RBD antibody and soluble hACE2 receptor.

Intramuscular injection of rMVA into mice induces antibodies, neutralizes pseudoviruses in vitro, and passively transfers hACE2 transgenic mice to lethal infection with SARS-CoV-2 and S-specific CD3 CD8 IFNgT cells. Protected from.

Antibody boost occurred after the second rMVA or adjuvant purified RBD protein. Immunity given by a single vaccination of hACE2 mice prevented morbidity and weight loss during intranasal infection with SARS-CoV-2 after 3 or 7 weeks. One or two rMVA vaccinations prevented the detection of infectious SARS-CoV-2 and subgenomic viral mRNAs in the lungs and significantly reduced the induction of cytokines and chemokine mRNAs.

A small amount of virus was found in the turbinate of only one of the eight rMVA-vaccinated mice on day 2 and was not found thereafter. Detection of low levels of subgenomic mRNA in the turbinate indicated that replication was arrested in immunized animals.

Recombinant DNA methods have revolutionized the engineering of vaccines against microbial pathogens, thereby creating opportunities to control the current Covid-19 pandemic.

The main categories of recombinant vaccines are proteins, nucleic acids (DNA and RNA), viral vectors (replication and non-replication), and live transgenic viruses. Each approach has advantages and disadvantages in terms of manufacturing, stability, cold chain requirements, inoculation methods, and immune stimulation. Recombinant proteins have been successfully deployed as vaccines against a variety of diseases.

DNA vaccines are licensed for veterinary purposes, but none are commonly used by humans. A recently developed messenger RNA (mRNA) vaccine is used in Covid-19 and is in the preclinical development stage for other infectious diseases. At least 12 viral vector vaccines based on adenovirus, poultry virus, vaccinia virus (VACV), and yellow fever virus have veterinary uses, but so far, especially attenuated adenovirus and VACV, It is posted online at ClinicalTrials.gov.

Various recombinant approaches that utilize the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; CoV-2 for short) as an immunogen are being investigated to calm the pandemic of Covid-19. It has been.

Vaccines based on mRNA and adenovirus vectors have shown promising results in clinical trials and have been approved by emergency regulators. Other candidate CoV-2 vaccines, including those based on vesicular stomatitis virus, alphavirus-derived replicon RNA, inactivated recombinant Newcastle disease virus, and modified VACV anchorage (MVA), are in the early stages of evaluation.

Experiments with viral vectors for vaccination were first conducted with VACV and set a precedent for many other viral vectors.

Most of the current VACV vaccine research employs MVA strains. This strain was attenuated by passage over 500 times in chicken embryo fibroblasts, during which time numerous genes were deleted or mutated, making it unable to replicate in humans and most other mammalian cells.

Despite being unable to complete a productive infection, MVA can highly express recombinant genes and induce an immune response. MVA is an approved smallpox vaccine and numerous clinical trials of recombinant MVA (rMVA) vectors are underway or completed.

MVA-based SARS-CoV-1 and Middle East Respiratory Syndrome CoV (MERS-CoV) in animals provide protection, and MVA-based MERS-CoV vaccine may be safe and immunogenic in Phase 1 clinical trials Shown.

Currently, two clinical trials of the MVA-based CoV-2 vaccine are in recruitment (ClinicalTrials.gov). Here, one or two immunizations with rMVA expressing the CoV-2 S protein elicit a strong neutralizing antibody response, induce CD8 T cells, and kill susceptible transgenic mice with the CoV-2 virus. Demonstrate protection from common intranasal challenges and support for relevant clinical trials. rMVA vaccine.

K18-hACE2 transgenic mice are an incomplete model of human susceptibility to CoV-2, and viral inoculation that caused severe morbidity and mortality within 5 to 6 days occurs during human infection. May be higher than.

Lack of signs of morbidity, failure to detect infectious CoV-2 in the lungs, and reduced levels of cytokines and chemokines in the lungs of vaccinated mice are consistent with pathological prevention, but the latter Pulmonary function test or histological test.

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