Very simply – how vaccines work

As a chemist, I thought that I should reach to my vocation and discuss how the adenovirus- and micro RNA-based vaccines for COVID-19 work. I have tried to keep the language as simple as possible, but would be happy to field any queries that anyone may have. Please email me at s.chandra@cqu.edu.au and I will do my best to answer.

The Adenovirus Vaccine (used by Oxford/AstraZeneca and Johnson & Johnson, J&J)

Basically, the AZ (and related Covishield) use the adenovirus from chimpanzees. They added the DNA from the coronavirus spike protein (shown to the right, below) to this adenovirus, which can then enter human cells but not replicate. The adenovirus has a tough coating which protects the DNA from the handling and weather elements (like hot conditions). This is also why the AZ vaccine is suitable for hot climate conditions like Fiji.

Essentially, the non replicating adenovirus sits comfortably in the vials until it is injected. Remember, the adenovirus itself is not a fully-functional virus. It is merely a carrier, and because it is less than 100 nm in overall size, it can even be called a nanocarrier!

What happens when the vaccine is put inside a syringe and injected with a person?

Coronavirus structure (Corum and Zimmer, 2021)

As soon as the vaccine is injected inside a human, the adenovirus comes into contact with the cells of the human body. The cells immediately react to this adenovirus and capture it. The adenovirus then makes its way to the nucleus (the ‘heart’ of the cell really) where the cell’s own DNA is stored. There, the adenovirus pushes its payload (the DNA it was carefully protecting) into the nucleus. The cell reads the DNA information and copies it into a messenger RNA molecule, called mRNA.

So, effectively, the adenovirus here acts almost like a USB-stick carrying the information of the coronavirus that it came from. It’s role is to transport the coronavirus spike protein gene to the ultimate destination, the nucleus of the human cell.

Back to the mRNA. It leaves the cell with the coded information that it was ‘given’ by its cell, and starts to assemble (scientific word for ‘make’ or ‘manufacture’) spike proteins. Remember, the DNA from the coronavirus was about the coronavirus’s own spike protein, and thus, the mRNA can only pretty much copy-paste what it was given. That is why it ends up producing the same spike proteins.

Because the spike proteins that the mRNA produces are foreign to the human body, they stand out.

Now the human body is quite clever and knows really quickly when something that isn’t meant to be inside it gets in. That’s what we call an immunological response (or commonly, an allergic reaction). It picks out the spike protein produced by its own mRNA, and immediately triggers its immune system to go and destroy it. All good, problem solved.

Adenovirus mechanism (Corum and Zimmer, 2021)

Remember that before the adenovirus was injected inside the human body, the human body had no idea what a coronavirus was, let alone how to deal with it! But, after it was injected with the adenovirus, which also brought the coronavirus spike protein information with it, the human body was able to produce spike proteins itself, and then realize “hang on, what is this crap? I don’t know it, I don’t like it, let me destroy it”.

More actions continue to be taken by the injected human body against the spike proteins, but very simply, after this experience, it knows what a spike protein is, and more importantly, it is ready!

So, this means that later down the track, if the injected person (who we can now correctly call a vaccinated person) gets an actual coronavirus inside them, their body remembers what it must do to destroy the virus. Previously, it did not have the ability to do so.

In this manner, the vaccinated person, when exposed to foreign viruses, does not suffer any adverse reactions and can get well much much sooner than an unvaccinated person. At times, vaccinated people may get exposed to such viruses but not even have symptoms because their bodies have instantly kicked the virus out.

That is also why vaccinated persons are said to not suffer as much as unvaccinated persons.

Now all humans are different, and so are their bodies. This is why most people respond well to vaccines, but some not as well, and suffer from other issues when vaccinated, such as blood clotting. Evidence indicates that these persons already have severe risk of clotting anyway. They probably were not aware of it.

Reference

Corum J, Zimmer C. How the Oxford-AstraZeneca Vaccine Works. The New York Times, New York, 2021.

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The micro RNA (Pfizer/BionTech and Moderna) Vaccine

The micro RNA (miR) vaccine works similarly to the adenovirus-based vaccine discussed above. It also delivers the genetic material to a human cell (via injection of course). The key differences in the miR vaccine are:

  • There is no nanocarrier such as a non-replicating adenovirus involved in ‘couriering’ the genetic material to the human cells
  • The genetic material being injected is not in the form of DNA, but as miR

Once the miR is delivered to the cell nucleus, it ‘teaches’ the cell how to assemble spike proteins. The end result is the same as what happens in the above example. The cells start to make spike proteins similar to those on the coronavirus. The proteins are often large molecules and in the large numbers that they exist in, it isn’t long before the body ‘notices’ the new protein, and immediately activates the its immune system. The rest of the process thus consists of the body taking over and fighting the protein that it sees as the infection. The body fights the protein by simply destroying it. Proteins are easily broken down (called denatured) by the simplest changes in their molecular structure, so destroying proteins for the body is a simple task.

Anyone who has studied chemistry at high school or university would remember that they tend to be very complex, large molecules. This is how they are picked up by the body’s ‘immunity radar’. The adenovirus (in the case of the AstraZeneca or J&J vaccines) are rather small (nano-sized), so they tend to escape the body’s radar. The same applies to the very small miR molecules injected in the Pfizer or Moderna vaccines).

The cells that have the job of destroying foreign matter in bodies (including assembled spike proteins) are called phagocytes. Phagocytes are the body’s ‘soldiers’.

So what is a miR shaped like? An miR is a chain molecule, single-stranded. It is simply a collection of molecules called bases. There can be four bases in an miR chain, and these include adenine (A), cytosine (C), guanine (G) and thymine (T). These bases can occur in various combinations, but the order in which they are located in the chain (called sequence) is important.

For example, a small chain of 3 bases made of A, G and T could either be as below:

  • A, G, T
  • A, T, G
  • G, T, A
  • G, A, T
  • T, A, G
  • T, G, A…etc.
DNA strand with recognition sequence highlighted in blue and single strand miR with base pairing count per mer used in the study. Red color indicates mismatches in sequence. Arrows denote the direction the miR is meant to be read in. (Reproduced from Chandra and Adeloju, 2020)

I have worked with miRs before, and this paper shows a recent work we have published where miR were used as biomarkers for determining early onset of Parkinson’s disease. The table shows some possible miR chains that we used. They may seem long, but believe me, for miR standards, they are actually quite short. The table also lists a few DNA sequences, where the thyamine is replaced by another base, uracil (U).

On the topic of immunity radars, some people do not have very alert immune systems – this is one of the reasons why for them, vaccinations do not work very effectively.

Others have hypersensitive radars – their bodies trigger extreme allergic reactions which can include blood clotting. These are the reasons why vaccine details include the efficacy rates (how effective the vaccine is) and allergic reactions. For example, the success or efficacy rates of the AZ vaccine against the Alpha variant has been reported by AstraZeneca as being around 70% (AstraZeneca, 2021). That means that if 100 persons were administered the drug, about 30 persons would not have their immunity becoming capable of resisting the alpha Variant of COVID-19 causing coronaviruses. The reasons for these would largely be based on these persons’ bodies and physiology.

Reference

AstraZeneca. AstraZeneca’s COVID-19 vaccine shows effectiveness against Indian variants of SARS-CoV-2 virus. 2021, 2021.

Chandra S, Adeloju S. A new sensor for detecting microrna 133B (Parkinson’s disease biomarker). Sensors International 2020; 1: 100005.