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RNA vaccine against COVID-19

What is an RNA vaccine? 

Unlike previous vaccines, they don’t contain whole microbes or even fragments. They are made of a genetic sequence, a messenger RNA (mRNA), with the information to produce a protein, in this case, of the coronavirus. The mRNA is wrapped up in a fatty layer, a lipid capsule, to protect the mRNA. When injected, the mRNA enters the host’s cells where its message is ‘read’, making the cells produce proteins based on the information on the mRNA. In this case they make a coronavirus protein. The coronavirus protein floating around the body acts just like every other vaccine and stimulates the immune system.

Adjuvants are substances sometimes added to vaccines to increase their effectiveness. Unfortunately they can also sometimes cause side effects. RNA vaccines have the advantage of inducing a strong immune response without the need for adjuvants. RNA is chemically similar to DNA but much more fragile. It is only present for a very short time in the cell because it is recycled quickly. It doesn’t alter the host DNA nor does it stay in the body for long periods of time.

RNA vaccines are not only easier and faster to manufacture than conventional vaccines, they are also easier to adapt. This is a clear advantage in the context of a pandemic. Conventional vaccines usually require expensive and time-consuming steps. The target virus  needs to be cultured in a lab. With the RNA vaccine mRNA can be produced and packaged in very little time. And if the virus evolves, the vaccine can be easily adapted by simply changing the sequence to fit the mutation. This is a huge improvement.

Moderna, for example, managed to create a vaccine within just four days of receiving the SARS-CoV-2 genome sequence. Collaborating with the US National Institutes of Health, the company then ran proof-of-concept experiments in mice before kicking off first-in-human testing in a span of just two months.

When was the RNA vaccine first invented?

The idea for RNA-based vaccination dates back to the 1990s. At the time, researchers in France first used RNA encoding a flu virus in mice. It produced a response, but the lipid delivery system used at the time proved too toxic to use in people. It would take another decade for companies to develop the safe lipid capsules used today.

The first RNA vaccine, as we know them today, was developed in 2012. Scientists successfully vaccinated rats against a respiratory virus. About a year after that, a new strain of avian influenza – bird flu – appeared. Scientists at Novartis’s US research hub in Cambridge, Massachusetts decided to put their new vaccine to the test. In less than a week they were able to synthesize the RNA for the vaccine, assemble it and test it in cells. A week later they were testing it in mice.

The development happened at a breakneck speed. The Novartis team achieved in one month what typically takes a year or more. But at the time, the ability to manufacture clinical-grade RNA was limited and unfortunately the research was halted in 2015 when Novartis sold its vaccines business. The work was never tested in people.

However, two smaller firms continued to work on the RNA vaccine technology. One was CureVac in Tübingen, Germany, which began human testing of a rabies vaccine in 2013. The other was the now famous Moderna, who managed to bring an RNA-based vaccine for a new strain of avian influenza into clinical testing in late 2015. It created strong enough immune responses that the company moved ahead with human trials of RNA vaccines for the cytomegalovirus (a common cause of birth defects), two mosquito-borne viruses (chikungunya and Zika) and three viral causes of respiratory illness in children. GlaxoSmithKline, which had acquired most of Novartis’s vaccine assets, also began evaluating an RNA-based rabies vaccine in 2019.

By the beginning of 2020, about a dozen RNA vaccine candidates had been tested in humans. Four had been abandoned after initial testing. The cytomegalovirus RNA vaccine was the only one that had progressed to a larger, follow-on study.

It took a global pandemic and the emergency fast tracking of the technology, for RNA vaccines to prove their worth. They are now on the front lines in the fight against COVID-19 after winning approval from regulators in several countries around the world.


Last edited: 29 January 2021 13:17

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