Deleting the 5 Letters of COVID-19 (ATCUG)

The media is bombarding us daily with two messages on opposite sides of the coin. One message displays record-high infection rates due to COVID-19, while the other focuses on the release of messenger RNA (mRNA) vaccines initially by Pfizer-BioNTech, followed by Moderna. With so many drastic changes to our lives, I believe it is always good to understand what, how, and why things are done. This blog post will go over what the mRNA vaccine is, how these types of vaccines differ from traditional vaccines, and why they can be advantageous. If you haven't read our first blog post - The 5 Letters of COVID-19 (ATCUG) – I previously introduced how the COVID-19 virus was detected and how the tests work.

By now, I'm sure most people have heard of the new mRNA vaccines that are being developed and have been released for emergency use. However, this is the first time an mRNA vaccine has been FDA approved, which is quite exciting. RNA vaccine research has been around for quite a while, so it's not as new as you might think; this is why so much could be done in such a short period of time. Of course, traditional vaccines and mRNA vaccines differ from one another, specifically in manufacturing and the initial steps after inoculation, but not with respect to how immunity is generated. The majority of previous vaccines we are used to are live attenuated vaccines, inactivated vaccines, and subunit/conjugated vaccines. Live attenuated vaccines contain a weakened living form of the virus, inactivated vaccines contain the "dead" disease-causing agent (virus or bacteria), and subunit/conjugated vaccines contain a part of the disease-causing agent. On the other hand, mRNA vaccines are made from RNA, the genetic material that our body uses to carry around instructions for building proteins. Typically, you are injected with a virus or viral protein, and your body produces an immune response to this. However, with an mRNA vaccine, your body becomes a factory for the production of the viral protein, allowing your body to mount an immune response without any risk of infection. The reason why there is no risk of infection because the viral protein made from the mRNA vaccine is only a portion of the virus' spike protein, which means that there is no virus present to infect you.

The most significant advantage of mRNA vaccines is the manufacturing time. Conventional vaccines require time for production as the virus needs to be grown and reproduced in a lab setting. This is because the virus is a part of the vaccine itself, either as a weakened or inactivated whole or as a subunit. On the other hand, once developed, mRNA vaccines can be easily synthesized and used for inoculation. However, one of the drawbacks of mRNA vaccines is stability. Since the main component is genetic material, it becomes unstable at elevated temperatures; this is why these vaccines are stored below freezing temperatures. Not so bad of a trade-off when you're trying to vaccinate a majority of the planet if you ask me.

Shown below are the different ¹H NMR spectra of each nucleoside, very similar to nucleotides (a building block for DNA/RNA) but without the phosphate group. Regardless, the ¹H NMR spectra of these compounds would look relatively similar with or without the phosphate group. These spectra were obtained using the 60e! Unfortunately, we do not have access to the nucleotide sequence that they use for the mRNA vaccines, but it would essentially be a long chain of the molecules shown below (except for thymine, that's just for DNA).

Figure 1. ¹H (60 MHz) NMR spectrum of guanosine in DMSO-d₆.

Figure 2. ¹H (60 MHz) NMR spectrum of adenosine in DMSO-d₆.

Figure 3. ¹H (60 MHz) NMR spectrum of cytidine in DMSO-d₆.

Figure 4. ¹H (60 MHz) NMR spectrum of uridine in DMSO-d₆.

Figure 5. ¹H (60 MHz) NMR spectrum of 5-methyluridine in DMSO-d₆.

As you can see, the slight differences in structure between each nucleoside are easily distinguished by ¹H NMR spectroscopy.  If you think about it, this is essentially life through the eyes of an NMR spectrometer. NMR spectroscopy can give us so much information; not only is it inherently quantitative, but it is also a phenomenal technique for structural elucidation. With a single experiment, NMR spectroscopy can give you details about the absence/presence of a chemical species (such as impurities), quantify chemical species, identify functional groups, and inform on connectivity and spatial arrangement. All this information, gathered using only NMR spectroscopy, would otherwise require multiple types of analyses and different techniques, demonstrating how powerful this approach truly is. If you have any questions about NMR spectroscopy and how it could work for you, please don’t hesitate to contact us!