COVID-19 Blog Series: Part 2

Blog part 2: Fighting back: Training our immune system with vaccines against SARS-CoV-2

Disclaimer: This blog is for information purposes only – please consult a medical professional for advice if you are concerned about COVID-19 or vaccine suitability. 

In the last blog we saw how our immune system can fight back against SARS-CoV-2. But for some people this will mean getting unwell during their initial infection, and as we know, COVID-19 can be fatal especially in at-risk groups. So, what we want is to teach our immune system to recognise SARS-CoV-2, by inducing immune memory – to protect us from future disease or infection but without risking illness. Well, we have just described the point of vaccination! Vaccines come in several types – and this depends on what we are trying to gain immune memory of, but the aim is to give patients parts of the infectious agent (also known as a pathogen- from the Greek, ‘Pathos’ – ‘suffering’ and ‘genes’- ‘producer of’) or a weakened version of the pathogen.  

Due to a huge international effort, we now have multiple vaccines against SARS-CoV-2 some of which are licensed in the UK. These vaccines are mostly training our immune system to recognise parts of the spike protein (see below for a picture). This is a part of the virus surface that sticks out and is what it uses like a key to gain access to the inside of our cells (by binding to our own ACE2 protein). So, this is a good part to target with a vaccine as antibodies made against the spike can block this interaction, stopping the virus entering our cells.  

Illustration of a coronavirus based on what is seen via a very high-level microscope (electron microscope) – showing the Spike protein, shown here as ‘S’ 

There are lots of different ways to make a vaccine with different methods to introduce the protein or genetic instructions to make it.In the UK we have 3 vaccines authorised for supply so these are the ones we will focus on but some great sources to find out more are: 

mRNA Vaccines 

Two of the three vaccines available to us in the UK (Pfizer-BioNTech and Moderna) are mRNA (messenger ribonucleic acid) vaccines. mRNA, is made by interpreting the information stored in DNA into an RNA form. This mRNA then acts like a short-term instruction to make a certain protein that can then fulfil a function – RNA isn’t all that stable, so this instruction doesn’t last long, which is important as we don’t want to make vast amounts of the same protein all the time! mRNA instructions are read in the cytoplasm of the cell – away from the nucleus where the DNA master copy is held, and our cells are not able to convert the RNA message back into DNA, meaning it can’t interact with or alter our own DNA. This is all important for how mRNA vaccines work. These vaccines consist of the mRNA instruction to make the SARS-CoV-2 spike protein and to help this get into cells it is packaged into tiny lipid droplets (lipid nanoparticles) that gives it access into our cells. 

Once this instruction is read and the spike protein is made our immune system can respond – just like we described in the part 1 of this blog series (Fighting back: The immune system’s battle against COVID-19 ). You can see how this works together in the diagram below (Figure 1). Other vaccines, like viral vector vaccines will trigger an immune response in a very similar way – it’s the delivery of the spike protein, or the way we get cells to make the spike themselves, that can be a bit different! Because of this immune response you can sometimes feel flu-like symptoms after vaccines in general, but this is just how our bodies respond to immune cells getting activated and this tends to go away quickly. 

The one snag with these vaccines is because RNA is so unstable the vaccines need to be kept very cold between –20°C (Moderna) to as low as -70°C (Pfizer-BioNTech) which means that they require specialist freezers. 

Text Box

We may be able to store these vaccines at more convenient temperatures in the future, but we don’t yet know how stable the vaccines are at warmer temperatures yet. This requires extensive ‘thermostability’ testing, putting the vaccine through its paces at different temperatures, and mimicking what the vaccine would experience while being transported/stored. Due to the urgent need for vaccines, this temperature testing isn’t finished yet, so vaccines are being stored at the most cautious temperature to be sure that they will still work properly. This testing has to happen in real-time, e.g. to understand whether we can store a vaccine in the fridge for 2 years, we need to do just that: store it in a fridge for 2 years! At the moment it’s a waiting game to try and make this type of vaccine more suited to use in areas that don’t have access to specialist freezers. 

But the great news is these vaccines are really effective at stopping us getting sick from COVID-19 with evidence for 94-95% protection for the Pfizer-BioNTech and Moderna vaccines 1,2,3

Viral vector vaccines 

Viral vector vaccines are a really exciting type of vaccine which actually use a virus to help us fight a virus! The idea is pretty simple: stick the DNA for the SARS-CoV-2 spike protein into a harmless virus so that our body gets chance to practice fighting the spike protein in a safe environment. The Oxford AstraZeneca vaccine uses this system, utilising an adenovirus from chimps to carry the spike protein DNA. This harmless virus can cause colds in chimpanzees but has been weakened for the vaccine and is unable to replicate itself in human bodies.  

When a virus infects us, it usually hops inside one of our cells to hide out and can hijack the machinery of this cell to halt the production of our human proteins and start to produce its own viral proteins. This is how a virus can replicate itself inside a body.  

So how can we safely use this system against COVID-19? The weakened chimp adenovirus can successfully enter our cells and hijack our cell machinery to produce the spike protein. This allows our body to detect the viral protein and mount an immune response against it, letting us gain immunity to the spike protein and work out the best way to neutralise it, without us ever having to be infected with the SARS-CoV-2 virus itself. The best part about it? It’s absolutely harmless! The spike protein on its own can do nothing at all; its production causes no harm to the body without the rest of the virus present. The adenovirus that carries the spike protein DNA is also harmless and is unable to replicate itself in a human body so can’t mount a proper infection in us either. This way, we are using the adenovirus’ ability to hijack our cells to let our body become immune to SARS-Cov-2. Pretty impressive right? 

Figure 2 How viral vector vaccines for COVID work

This vaccine works pretty well as far as we have seen. Even though the vaccine is supposed to be taken in two doses, even just the first injection has been shown to prevent two thirds of COVID-19 transmissions4. This does not mean you shouldn’t go back for your second jab though as this should boost your immunity even further! Another benefit to this vaccine is that unlike mRNA vaccines, it can be kept in a normal fridge rather than at –70°C freezer which makes transport and distributing the vaccine much, much easier. 

This type of vaccine is relatively new but has been built upon years of research and has already been used in the Ebola vaccine. Researchers at Oxford had actually been working on this type of vaccine for many years in case of a new disease like COVID-19 emerging and could easily modify the vaccine to include SARS-Cov-2 DNA when it was needed. Viral vector vaccines could become very useful in the future to help fight any new emerging diseases that pop up. 

The good news is these vaccines are good at promoting T Cell and B Cell responses which are both important in our defence against SARS-CoV-2 infection and COVID-19 disease as we saw in the last blog.  

These vaccines require a second dose which is important in promoting long term T and B Cell memory as well as helping our B Cells to improve their antibody ‘designs’. 

The development of these vaccines has shown how quickly we can respond to new infectious diseases by international collaboration of scientists and clinicians which is a cause for optimism for the future! In our next, and final COVID-19 blog, find out about the new ways we are finding to treat those who already have severe COVID-19.  

References  

  1.  Polack et al. 2020 Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine New England Journal of Medicine 383 2603–2615 
  1.  Dagan et al. 2021 BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting New England Journal of Medicine DOI: 10.1056/NEJMoa2101765 
  1. Baden et al. 2020 Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine New England Journal of Medicine DOI: 10.1056/NEJMoa2035389 
  1.  Hung IFN, Poland GA. Single-dose Oxford-AstraZeneca COVID-19 vaccine followed by a 12-week booster. Lancet. 2021 Mar 6;397(10277):854-855. doi: 10.1016/S0140-6736(21)00528-6. PMID: 33676614. 

British Society for Immunology – “A guide to vaccinations for COVID-19″ https://www.immunology.org/sites/default/files/BSIresource_A_guide_to_vaccinations_for_COVID19.pdf