Dec 14 2020

mRNA Vaccines

This week should see the first people in the US to actually receive an approved (at least EUA) vaccine to prevent SARS-CoV-2. There are three vaccines currently ready to go in the West, the Pfizer vaccine which received it’s EUA in the US on Friday and was already approved in the UK, Moderna which should get approval this week, and the Astra Zeneca vaccine which should not be too far behind. The (arguably) biggest challenge has been met – a massive scientific effort to develop vaccines in record time. This has been a collaboration between government and industry, and shows what we can accomplish with sufficient motivation (which translates into both money and easing red tape).

Now we have three further challenges in front of us. The companies need to mass produce their vaccines. This is happening with about 100 million doses ready to ship. We should have another 2 billion Pfizer doses by the end of 2021, and 1.5 billion Moderna doses. We also need to distribute the doses. This is happening through collaboration among FedEx, UPS, and the military who will get the doses to hospitals and physicians, who can then administer and track the doses. So far, so good.

The final hurdle, however, may prove the stickiest – we need people to accept the vaccine. In a December 9th survey by the AP-NORC, only 47% of Americans said they would get the vaccine, with 26% saying they would not, and 27% saying they are not sure. These and similar results have caused some to comment that the disinformation virus may prove deadlier than the COVID virus. We have a vaccine that can protect people from a deadly pandemic – this is a no-brainer. Resistance is partly due to a dedicated anti-vaccine movement that appears immune only to logic and evidence. We can only marginalize them. But these numbers go beyond the hard-core anti-vaxxers. People also fear what they don’t know, and these are the first mRNA vaccines to hit the market. So let’s review what these are, and the safety data.

Vaccines basically work by exposing the body to antigens (something to which the immune system can react) that are found on an infecting organism so that the body can mount an immune response, including memory for those antigens. This will allow the body to respond more quickly and robustly when exposed to the living organism, fighting it off before a full-blow infection can occur. Antigens can be a weakened and/or altered form of a virus, an inactivated virus, or isolated proteins from the surface of a virus or bacteria. These exposures are often given with adjuvants that help stimulate the immune system to maximize the response. They may also be given in multiple timed doses to maximize immune response. The immune memory will then last for a variable amount of time, depending on the organism and the vaccine (typically years).

The mRNA vaccines are just a novel way of getting antigens into the body to provoke an immune response. Instead of injecting proteins, you inject mRNA – RNA is similar to DNA, one form of the genetic information that codes for each organism. You have DNA in most cells in your body (some cell types, like red blood cells, lose their nucleus and so have no DNA). DNA is like a repository of the code, while RNA does the work. The “m” in mRNA stands for messenger. These RNA strands are made from the DNA, they travel outside of the nucleus onto the cytoplasm where their code is converted into a string of amino acids, which is then folded into a protein.

If you inject mRNA which codes for a specific protein into the body, and this mRNA is then taken up into cells, the machinery of those cells will make protein from the introduced mRNA. The mRNA vaccines, therefore, introduce the code for a viral protein that will provoke an immune response. So instead of injecting the protein, you inject the mRNA which then gets translated into the desired protein. The vaccines use mRNA for the spike protein on the SARS-CoV-2 surface, and they also include a shell that protects the mRNA from being degraded and helps it get into the cells. Why would we do it this way? One reason is that we are really good at making RNA, and it can actually be easier, faster, and cheaper than making proteins.

Here are a couple of important points: The mRNA will mostly be absorbed by muscle cells near the point of injection. The half-life of mRNA in humans is about 10 hours, so it will be gone in a matter of days. The mRNA never gets into the nucleus of the cells, and so it has absolutely no effect on the DNA. It is therefore entirely wrong that the vaccines can alter our DNA, as some anti-vaxxers are saying.

Also, while these vaccines are new, mRNA technology has been researched for years. The company Moderna was founded in 2010 purely for mRNA technology, and so has been developing that technology for the last decade – even though their COVID vaccine is their first commercial product. The mRNA technology can also be used for more than vaccines – any protein-based therapy can be achieved through mRNA.

Regarding the safety of the vaccines, the two mRNA vaccines together have followed about 70,000 subjects for at least two months. This time frame was chosen by the FDA because most vaccine side effects are apparent by 6 weeks from the time of injection. By their calculations, this is a good safety buffer. No serious side effects have emerged.

This does not prove zero risk. There is never zero risk. But we have to make a risk vs benefit analysis. While side effects may emerge once millions of people get the vaccine (and yes, this will be tracked), the data we have sets statistical limits on how frequent those adverse events can be. We can compare this to the risk of contracting COVID. In the US about 1 in 20 people have caught the virus, and the death rate is on the order of magnitude of 1 in 1,000. That is many times mores than the greatest side effect rate of the vaccines. Even if you are in a low risk group, you are statistically more likely to benefit from getting the vaccine than to be harmed by it. (Keep in mind, death is not the only outcome – spending time in the hospital is very inconvenient, and many people survive but have long term health consequences.)

But people are risk-averse, and are more afraid of the risk of an action than a non-action. But we don’t have to rely on our evolved instincts – we can crunch the numbers. It is more risky to not get the vaccine than to get it. And the mRNA technology is well understood and safe – and it does not affect your DNA. Further, the vaccines are our shortest route out of this pandemic and all the downstream negative effects of that, including on education, our economy, and our future. Seriously – get the COVID vaccine as soon as you are able.

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