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Covid-19 Vaccines

Two new approaches to a Covid-19 vaccine: how do they fit in?

In a frenetic two weeks, when results of one successful approach to making a vaccine based on RNA dominated the media, comes news of two other different pathways, each with their own promise. That is on top of the Oxford vaccine that was ‘first off the blocks’ with results due ‘anytime’.  In this post I take stock of where we are and provide what I hope is a really simple guide to these different approaches and what each could bring. 

The starting point: the common enemy – the Spike Protein

  • From the beginning of the Covid-19 outbreak, it was discovered that this virus has a number of proteins
  • Importantly it is covered in spikes which allow the virus to enter our lungs and other organs and start spreading
https://coronavirusexplained.ukri.org/en/article/cad0010/
  • If we could target the spike protein we could get rid of the virus from the body
  • The way to do this was to use a vaccine that would lead the body to develop antibodies against the spike protein, and when people who had been vaccinated came into contact with the virus the antibodies targeting the spike protein would emerge and do their stuff

What were the choices?

There are 5 different ways that success could be achieved: each one aiming to be a safe and effective way of leading to antibodies. They are using a vaccine that delivers one of the following: 

  1. A weak form of the virus
  • This is the traditional approach to making a vaccine and is now being tried for Covid-19 
  • The aim is to produce a safe vaccine from either a dead form of that virus, or a live virus that is sufficiently similar to produce the necessary antibodies, but not dangerous enough to produce a Covid-19 like infection
  • Takes a lot of testing to produce the right final product
  • Not always effective
  • Worries about safety and whether any weak form of the virus would be harmful to some people
  • Nonetheless tried and tested  approach and could be quite cheap to produce 

2. DNA from the virus for the body to start making its own spike protein

(In a post published alongside this one I have provided an easy to follow guide to how DNA and RNA vaccines work to produce the spike protein, which you may find helpful to understand the science behind these different approaches)

  • This is the basis of the Oxford/Astra Zeneca vaccine
  • In a very novel approach, only really tried with Ebola, the developers added the DNA sequence that is needed to produce the Covid-19 spike protein to a harmless virus
  • Thus, when this harmless virus was injected into the body, it would produce the spike protein, but not other parts of the Covid-19 virus
  • We know that the approach is successful in producing antibodies against the spike protein, we are waiting to see how successful it is in preventing infections with Covid-19
  • Even the harmless virus with the new bit of DNA could be excreted by those who are vaccinated, but worries about whether this is going to be harmful seem to be unfounded from what we know  

3.  RNA from the virus for the body to start making its own spike protein

  • This is the basis of the Pfizer and Moderna vaccines
  • This is an even more novel approach 
  • The vaccine does not involve a virus at all, but just the RNA from the virus sequence that is needed to produce the Covid-19 spike protein
  • We now know this is very successful in the short term at preventing infection
  • Because it bypasses the DNA stage of protein production, it removes one risk that the instructions for making the protein literally* “get lost in translation”
  • Also, because no virus is involved at all, it should be very safe
  • RNA is however unstable and that is why the Pfizer vaccine needs to be kept deep frozen.  Moderna have found a way to keep it just cold for a short while though
  • At the moment RNA vaccines are expensive to produce

4.  The actual (or a version of the) spike protein

  • An obvious question is why bother going down the DNA or RNA route, why not just make the spike protein artificially and give that as a vaccine?
  • The answer is that this is possible (the company Novavax issued a press release earlier this month)
  • A vaccine using this approach is in advanced development and the US government have given Novavax $2 billionto produce it
  • One problem is that the protein on its own will probably not produce a sufficiently large antibody response
  • Thus the vaccine needs to include other chemicals that will give a greater ‘push’ on the immune system to produce antibodies
  • This is not an unusual approach for vaccines: for example tetanus and diphtheria vaccines are based on giving harmful proteins (‘toxoids’) and not part of the infecting bacteria themselves
  • A vaccine like this could be very stable and cheap to produce but we have no idea if this one will work

5. Just give the antibodies so the body doesn’t need to make its own 

  • Another obvious question – if the challenge is to get the body to produce antibodies, why not give antibodies as a vaccine?
  • Indeed, newborn babies are protected against so many infections from the antibodies passed down from the mother
  • Antibodies injected into the body will not last very long – maybe months, maybe longer – but this approach could be useful to give short term protection
  • This might be useful in people who
    •  react badly to other vaccines
    •  have some problem with their immune system 
    •  may need special protection – I am guessing but for example a specialist doctor in an intensive care unit during a pandemic but for whom the normal vaccines did not work
  • This approach is very expensive, could be £/$’000’s per shot
  • Trials of this were announced just yesterday 

Conclusions

Yet more vaccines I am sure will create some confusion about which is best and ‘which should I have?’ What this post aims to show is that for this fundamental strategic approach to getting rid of the virus, we have so many different possibilities – that has to be good news!

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