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Circular RNA vaccines against SARS-CoV-2 and Emerging Variants
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Circular RNA vaccines against SARS-CoV-2 and Emerging Variants.
Use the “circular RNA” technology to create a vaccine against the “receptor binding region” of the spike protein of the new coronavirus (SARS-CoV-2).
1 Next-generation RNA vaccine technology
On March 16th, on the bioRxiv preprint platform, the latest scientific research results from the team of Professor Wei Wensheng of Peking University were published in advance. 
Professor Wei’s team used the “circular RNA” technology to create a vaccine against the “receptor binding region” of the spike protein of the new coronavirus (SARS-CoV-2).
In animal experiments, two doses of circular RNA were injected intramuscularly After the second booster immunization of vaccine mice, a large number of neutralizing antibodies are stably produced in their bodies, which can effectively neutralize the SARS-CoV-2 pseudovirus, indicating that the antibodies induced by the vaccine have strong virus neutralization ability.
Not only that, the circular RNA vaccine can also induce a powerful T cell immune response (mainly Th1 immune response, without stimulating Th2 immune response).
Because the current new coronavirus has mutated, and there are data showing that for the mutants (B.1.351/501Y.V2 and P1) that appeared in South Africa, Brazil and other places, the current protective power of the new coronavirus vaccine has declined.
In response to this severe situation, Professor Wei’s team also designed a new vaccine (circRNARBD-501Y.V2) against the 501Y mutation in the new strain of B.1.351, and compared it with the vaccine against the primary virus (circRNARBD).
The sera of vaccinated mice were collected to compare the neutralization ability of different antisera against different viruses.
The results of the research team showed that the vaccine against the primary virus did not have the ability to resist the new mutants (and did not disappear). , And the vaccine against the new mutation has the strongest resistance to B.1.351, and it is still resistant to the original and other mutations.
2 What kind of technology is circular RNA?
RNA molecules that can be translated to make proteins are generally single-stranded linear molecules, but some viruses, such as hepatitis D virus, can produce circular RNA molecules. Circular RNA molecules are very stable.
In a sense, this “circular RNA” technology is also the result of stealing viruses.
However, the skills of copying the virus are not enough. In order to defeat the virus, innovation is needed.
Therefore, in the “circular RNA” manufactured by the new technology, the “internal ribosome entry site” (IRES) required for protein translation and the m6A modification of the upstream sequence are added.
As a vaccine RNA, it needs to encode a protein of the virus as an antigen that triggers the immune system to produce antibodies.
However, in a “circular RNA” vaccine, it does not simply encode a “receptor binding region” required by the new coronavirus to infect cells. , But contains a phage protein pattern that helps it form a trimer.
Through this design, after entering the cell, the circular RNA vaccine can 3D print a realistic antigen protein, which is very consistent with the structure when the virus infects the cell, and the antibodies produced by the immune system can also better fight the virus.
3 Regarding the new technology of circular RNA vaccines, there are several points to be aware of
Nowadays, the COVID-19 vaccine is already on the market, and large-scale vaccination has begun worldwide. What is the significance of this new technology of Professor Wei’s team?
Although there is basically no epidemic situation in China, the global epidemic situation is endless. Although the epidemic situation is showing signs of improvement after the promotion of vaccination, the current B.1.351 and P1 strains have acquired the super ability to infect mice[2 ].
It is foreseeable that the fight against COVID-19 is not a short-term human behavior.
Although the strict prevention measures implemented by China are very effective, the social and economic costs are relatively high and cannot be implemented for a long time.
Both China and the world need to keep vaccinating against COVID-19.
Judging from the results of the current Phase 3 clinical trials, the new mRNA vaccine can obtain higher protection rate data (94%-95%), which means that the epidemic can be better controlled.
And these vaccines produced through genetic engineering have another advantage: they can quickly update the version of the vaccine against newly emerging mutant strains, which has a great advantage over conventional inactivated vaccines.
For example, if a new mutation is discovered in the virgin forest area of Brazil, if you want to update the conventional vaccine, you need to get the real virus strain.
This is a problem in today’s current international communication with huge obstacles. Even if it took a few months to get the virus strain, it would take two months to expand the cultivation of the live virus.
But for circular RNA technology, you only need to get the mutation sequence of the virus, and you can arrange to make an upgraded version of the vaccine.
This time advantage means that a more effective vaccine can be produced in the first time, and the epidemic can be extinguished faster.
It also means that more lives can be saved.
Obviously, this technology can also produce vaccines against other pathogens.
2） Compared with current mRNA vaccines, what are the advantages of circular RNA?
The mRNA vaccine needs to be stored and transported at ultra-low temperature. At present, it needs to have conditions of at least minus 20 degrees, which is a flaw in the accessibility of the vaccine.
But circular RNA is different, because it is very stable and does not require additional modification to RNA to improve stability.
The research team showed in the paper that after placing the circular RNA at room temperature for two weeks, the efficiency of transfecting cells did not decay.
This advantage will be very conducive to the development of future vaccines and is expected to become a vaccine that can be transported at room temperature and stored for a short period of time.
3）How long is the use of circular RNA?
Obviously, the current research is only an animal experiment. If the circular RNA vaccine can be used, it must first undergo necessary clinical trials.
Circular RNA vaccines against SARS-CoV-2 and Emerging Variants
(source:internet, reference only)