New candidate for LNP-based mRNA vaccine protects against deadly SARS-CoV-2 in preclinical trials

Although more than one brand of vaccines against coronavirus disease 2019 (COVID-19) pandemic was launched after allowing the use of growth, others continue to research to fill the worldwide need for effective worldwide deployment.

A new study, published in Nano Letters, describes an effective new vaccine candidate based on the messenger ribonucleic acid (mRNA) platform.

Severe acute respiratory distress coronavirus 2 (SARS-CoV-2) is transmitted to host cells by it protein on the spike, causes fuse of the viral cell membrane to accomplish viral entry through endocytosis. The spike communicates with the host cell receptor, the angiotensin-converting enzyme 2 (ACE2), in the receptor-binding domain (RBD), making it the basis of the current vaccine candidate.

The mRNA platform

With more than 3.5 million cases worldwide, meticulous research culminated in the launch of the first two vaccines allowed to be available in December 2020. The researchers focused on live-induced virus vaccines, inactive vaccines, recombinant viral vector, recombinant viral antigen, DNA vaccines and mRNA vaccines.

The mRNA platform has gained a lot of interest due to the ease of mRNA consolidation with current technological advances and advances in efficient delivery systems that allow mRNA to reach the cells at will. not yet rotten on the host.

The strand mRNA is designed to mimic host mRNA to avoid host detection. It does not have to be attached to the host genome, unlike vector viral vaccines. Plus, doing it is both quick and convenient.

The speed and speed of commercialization is a particularly significant advantage, demonstrated by the current pandemic, in which Moderna developed the mRNA vaccine and gave it to the first person in a clinical trial within 66 days from selecting the order of the virus.

The disadvantage of using mRNA is the rapid destruction of this molecule when exposed to host ribonucleases (RNases), which are present in all tissues. Second, mRNA is negatively charged and therefore resists entry into the cells themselves. It commands the use of a carrier molecule to protect it and carry it across the negative charge of the cell membrane.

Lipid nanoparticles

The use of lipid nanoparticles (LNPs) to encode viral mRNA encoding vaccine antigen is a remarkable advancement, and has been described for the development of multiple vaccines against human immunodeficiency viruses (HIV ), rabies, Zika and influenza viruses.

Not only do LNPs promote mRNA encapsulation and reduce the rate of crossing from the free cell membrane, they can even facilitate the escape of mRNA from endosomes into the host cell cytoplasm. , which is responsible for the translation of the vaccine antigen protein.

LNPs are composed of ionizable lipids (which stimulate the accumulation of self-contained LNPs), cholesterol to strengthen the particles, a phospholipid to support the double layer of the lipid structure, and a polyethylene glycol (PEG). -slip that lasts half -life of the structure.

Make a vaccine

In the vaccine formula described in the present study from Tel Aviv University, the mRNA encodes the recombinant spike RBD gene along with a fragment of the human antibody called the Fc (crystallizable fragment) component. This causes the antibody to bind to the spike antigen. Because the human Fc component has two binding sites, each hybrid molecule contains two RBD domains.

The mRNA was mixed with an ionizable lipid mixture to prepare lipop nanoparticles (LNPs) that encapsulate RBD-Fc mRNA. After vaccine administration, mRNA is transported to host cells, which express the RBD antigen to elicit a resistance reaction.

Earlier, the resistance resistance of this formula was tested in BALB / c mice. When administered intramuscularly, high antibody titers were observed, including a strong neutralizing response, and a Th1-skewed T cell response.

Study details

After confirming their internal expression in culture cells by examining their binding to purified IgG specific to SARS-CoV-2 spike protein, the same RBD-Fc-containing LNP preparation was performed. inoculate in mice expressing hACE2.

These animals were selected to express signs of severe illness, unlike hamsters and monkeys, which showed only mild illness.

In the present study, four groups of animals were inoculated with the vaccine, two administered any LNP-encapsulated RBD mRNA and two LNP-RBD-Fc preparations.

In each paired set, one group was given one dose, and another was given the same dose of priming and booster. Received controls by.

Serum samples were collected on day 23 and day 46 for the two dose groups, and the antibody response to the RBD vaccine was measured. Second, animals were exposed to the SARS-CoV-2 virus through intranasal inoculation, and signs of disease were examined. Animals showing signs of severe disease were released euthanized.

The study showed that mice developed a strong antibody response to the RBD-Fc mRNA antigen. Antibodies bound to hACE2 receptors had a high affinity, and neutralized viral infection in vaccinated mice following subsequent virus exposure.

In the vaccinated group, 70% showed protection against the lethal dose of the virus, compared with 100% mortality in the control group.

What are the effects?

The study reports on resistance and protection effectiveness of an LNP-based RBD-Fc mRNA vaccine in a mouse model expressing ACE2.

To the best of our knowledge, this is the first non-progressive mRNA vaccine study to report the protection of K18-hACE2 against the deadly SARS-CoV-2 infection., ”The researchers concluded.

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