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Is it possible to start manufacturing all vaccines only mRNA vaccines instead of the traditional ones using virus?
Question Date: 2021-03-26
Answer 1:

Great question. It sounds as though you know something about mRNA viruses, but I'm going to describe them for the benefit of anyone else who reads this.

Viruses are not alive and can't reproduce on their own. They work by turning their host's cells into virus factories. They inactivate the DNA in the host's cells and insert their own DNA or RNA, which is a set of recipes for making proteins. Standard vaccines work by injecting pieces of virus (or viral toxins) into a person (or any species). This is like showing a wanted poster to the person's immune system. The next time the person's immune system sees this shape, it will be ready to attack it. RNA or DNA vaccines work by injecting a RECIPE for a virus protein into the person. The person's own cells make a lot of a particular virus protein, way more than could be injected easily. The protein the cells make is harmless by itself, just like the picture of a wanted criminal isn't dangerous. It does not change the person's DNA.

The DNA/RNA vaccines are fairly new technology. Having the world-wide focus on this type of vaccination probably gave it a huge boost (some vaccine humor there--the second dose is a "booster"). The idea itself is amazing. The problems right now will probably be in the logistics of safely and effectively getting the mRNA into the cells. Another problem is that the virus's DNA or RNA can mutate. If a virus used to make a protein that looks like X, can it mutate so that it looks like Y, still work for the virus, but be invisible to a person's immune system? That's what people are worried about when they talk about variants of the virus.

Every time the DNA or RNA of a virus is copied, there's a chance for mutations. The more people infected by the virus, the more chance there are for a mutation that will change part of the protein in a way that a vaccinated person won't be protected. So our best protection against new variants is by stopping the spread. The more vaccinated people, and the more people making safe choices, the fewer chances there are for dangerous mutations to arise and for those new variants to spread.

If you could choose, what vaccine would you want to see next?

Thanks for asking,

Answer 2:

There is a principle in biology called the central dogma. It describes the flow of information in macrobiomolecules. For a typical organism to make a protein, it first transcribes some DNA into RNA and then translate the RNA into protein.

mRNA vaccine functions by delivering the mRNA transcript into a host cell so that the B cell will translate the transcript and present it as an antigen to the rest of the immune system. Therefore, in theory, as long as you can make the transcript for the foreign protein, you can make an mRNA vaccine.

However, the devil is in the details. There is a genetic code, where three nucleotides, a codon, corresponds to an amino acid. Amino acids are the constituent components of proteins. This code guides how DNA sequences will end up as a protein. Since there are 64 codons and 20 amino acids, some amino acids have more than one corresponding codons. The genetic code is almost universal. Besides some strange bacteria, any transcript can be expressed in any other organisms. However, when there are more than one codons, different organisms have different preference to which it is going to use. Furthermore, once the protein is made, many of them will undergo modifications without which they cannot become the correct antigen.

We not only make vaccines for viruses, we also make vaccines for bacteria. Although it is theoretically possible to express a bacterial gene in human, human cell might not be able to do it in peak efficiency. Furthermore, since bacteria are self-contained, human cell might not have the same enzyme necessary for the post-translational modification. Those factors will decrease the immunogenicity, the ability to induce an immune response, of the bacterial vaccine. On the other hand, since viruses relies on the host cellular machinery, all the necessary tools are already there and the codon preference will not be too far from the host.

Therefore, it is definitely possible to make any viral vaccine with mRNA vaccine. But for bacterial vaccine, that requires some work.


Answer 3:

Certainly it's possible that mRNA vaccines are an option for future vaccine development. First it's important to understand how the mRNA vaccines work.

By delivering mRNA coding for viral proteins, your body produces those proteins itself. The immune system then recognizes the new protein as foreign to mount a response and build up memory. So long as there is a potential protein target that can produce strong immune responses mRNA vaccines should work. Of course each vaccine will need to be tested individually to ensure that the protein produced by the coding sequence produces a strong enough immune response and also builds up strong enough memory to be effective. Sometimes a single protein or piece of protein isn't enough to produce a robust enough immune response, in which case an attenuated virus (a virus that is mostly whole but cannot infect you) may be a better vaccine candidate.

There is also a major drawback common to mRNA vaccines, and that is that mRNA is inherently very unstable. You've likely heard about the storage issue with the Covid mRNA vaccines that require ultra low temp storage and are more susceptible to expiring after thawed. This is a minor issue in most parts of the US but can be a real challenge in delivering vaccines to rural parts of the US and also less developed countries around the world.

Protein vaccines tend to be more stable as proteins are just naturally more stable and long lasting than mRNA. To fully utilize mRNA vaccines further advancements will need to be made in the preparation and additives of the vaccine to stabilize the mRNA long term or development of better infrastructure around the world to deliver the vaccines wherever they may be needed.


Answer 4:

Hi Mani, great question! At this point we cannot manufacture only mRNA vaccines. While it is not possible, mRNA gives a promising glimpse of the future. Recent advances have made mRNA vaccines more versatile than ever before. A huge benefit is being able to manufacture an mRNA vaccine in weeks. In the future mRNA vaccines may immunize us for several diseases with one shot! Even some cancer cells can be targeted by mRNA. One day Mani, mRNA vaccines may replace all the traditional ones. We need more data on long-term effects and manufacturing techniques.


Answer 5:

No, it is not possible.

Every virus is different, with its own capabilities and vulnerabilities. This means that the vaccine that will defeat one virus will necessarily be different from the vaccine that defeats a different virus. Whenever a new virus evolves, you have to develop a completely new vaccine in order to defeat it.


Answer 6:

Do we want to do that? What about traditional vaccines that are already made? Maybe we don't want to do the work of making mRNA vaccines for those diseases. But the 2nd link does suggest that mRNA vaccines have definite advantages.

Different vaccines.

mRNA versus traditional vaccines.



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