By Ewan Jones
It has now been over a year since the first cases of Covid-19 were reported, and in the meantime researchers the world over have been working faster than ever before to create a safe vaccine to hopefully aid us in returning to our normal lives. There are now over 200 vaccines in clinical and preclinical development (https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines), including six that have been approved for use in at least one country as of the 2nd of January (https://covid19.trackvaccines.org/vaccines/). Just within these six candidates there are multiple vaccination techniques being employed, and it can be difficult to distinguish how these diverse mechanisms work for their single purpose: to train your body to identify and fight Covid-19. In this article I’ll provide a quick rundown of the approved vaccines, including the different methods used by each through a hopefully simple metaphor…
So how do the vaccines compare?
The main areas of comparison between the approved vaccines are type of vaccine, efficacy (% reduction in disease in a vaccinated group compared to an unvaccinated group), cost, and storage requirements. The table below offers some insight into how five vaccine candidates that have passed phase 3 trials and are currently being given to individuals in a few countries stack up. Phase 3 data for Sinovac/CoronaVac have not yet been published, but as it has already been administered to hundreds of thousands in China under emergency authorisation (https://www.bloomberg.com/news/articles/2020-12-19/china-says-1-million-vaccines-already-given-plans-further-shots), I thought it should be included.
When it comes to efficacy, although it may seem alarming that some vaccine candidates, such as the Oxford/Astrazeneca jab, show ‘only’ 70%, this is in fact much higher than the best flu jab, which is only “about 50% effective” (https://www.bbc.com/news/health-55302595), and just about trumps the WHO’s ideal of “at least 70% efficacy in trials” (https://www.reuters.com/article/us-health-coronavirus-vaccine-efficacy-e-idUSKBN27S2EI). For comparison, the US FDA has set its efficacy cut-off at 50% (https://www.nbcnews.com/health/health-news/fda-s-cutoff-covid-19-vaccine-effectiveness-50-percent-what-n1245506).
What are vaccines?
Just a super-quick and simple introduction to vaccines before we dive into the different techniques on offer specifically for Covid-19, as well as an introduction to the vaccine metaphor. Imagine your body is an army general, waging war on an unknown enemy (Covid-19). Rather than foolishly trying to take on the enemy instantly, with no intel whatsoever, vaccines are the equivalent of gathering information on your foe before fighting them, allowing you to battle them much more effectively when you do come face-to-face.
Basically, vaccines train the immune system to recognise a disease without causing the symptoms associated with that illness, allowing the body to create the components needed to fight as soon as it encounters the disease itself. This is all due to the fact that your body’s immune system has ‘memory’ of how to fight diseases it has come across in the past; this is the reason why you can only catch, for example, chickenpox once in your life.
This ‘training’ of the immune system can be achieved through a number of different techniques (as evidenced by the array of vaccine types illustrated above), however they all work towards the same goal: allowing you to fight off a disease instantly and without serious symptoms, hopefully without you ever even realising you had it in the first place! So, what are the types of vaccines being used to fight Covid-19, and how do they fit into my flimsy metaphor?
Inactivated virus vaccines
An immensely popular option for vaccines, inactivated vaccines contain the pathogen (disease-causing agent, eg. the SARS-CoV-2 pathogen) itself. Of course, we can’t use a live pathogen, because it will just make you ill – scientists deactivate the pathogen using a range of methods (boiling works very well), rendering it safe. This inactivated pathogen can then be used to teach your body what the invader looks like, allowing it to prepare to fight the next time it comes in contact with the offender. As evidence of its widespread use, the UK flu shot is an inactivated vaccine (and you should definitely get one this year!).
In terms of the army metaphor, you can think of an inactivated virus as a defector from the enemy’s side – harmless to you, but able to give you information about the enemy, so that you can fight it more effectively when you come into contact on the battlefield.
One drawback of inactivated vaccines is that you need to start off with a large amount of live samples of the disease, which can take time and money to amass and keep safely contained prior to inactivation (https://www.nytimes.com/2020/12/30/business/china-vaccine.html).
This is where it gets more complicated. Rather than showing your body the pathogen itself, as in inactivated vaccines, mRNA vaccines use your own cells to produce their own vaccine, just like mini vaccine factories (this is my favourite type of vaccine, if it isn’t obvious)! So, back to biology basics: every living thing on Earth uses DNA as the ‘instructions’ used to make and govern itself. In order to turn the DNA ‘instructions’ into actual working parts, sections of DNA are ‘transcripted’ into RNA, which is basically a simpler form of DNA. mRNA is ‘messenger’ RNA, which carries these instructions to components in your cells that churn out proteins according to the instructions given. This process is repeated in every cell throughout your body. Okay, enough science!
mRNA vaccines are simply the RNA ‘instructions’ from the Covid-19-causing virus, which travel to your cells following injection. These then get turned into proteins from the virus that your body can recognise, allowing it to begin preparations to fight when it comes into contact with the virus, the same as in the inactivated vaccine. As with the inactivated vaccine, of course the instructions for making the entire virus are not injected into your body – instead we only use the instructions for the Covid-19 ‘spike protein’, which allows the virus to join with our cells and infect us. The spike protein alone can cause no harm to the body, but is sufficient to train our immune system to fight off Covid-19.
Back to the metaphor – an mRNA vaccine is like receiving intel about the unknown enemy, except it’s in their language. Your body, as the general, gets your top linguists to translate the information so that you can use it to your advantage when the time comes to fight.
mRNA vaccines are a double-edged sword in some ways. They can be made extremely quickly after the discovery of a new virus, as the only information needed is the genetic sequence of a pathogen, rather than masses of live virus as with inactivated vaccines. However, unlike inactivated vaccines, mRNA is very quick to break down, which is why vaccines using mRNA need to be stored at much lower temperatures than the other vaccine candidates (eg. the Pfizer vaccine).
Adenovirus vector vaccines
We’re at the final type of vaccine; it’s been a journey! Luckily the adenovirus vaccines are very similar to mRNA vaccines, also using your cells to produce their own ‘vaccines’. The difference in this case is how the instructions are delivered to your cells: whereas the mRNA vaccines are just that – mRNA in a simple coating – the adenovirus vector vaccines hide the instructions for the Covid-19 spike protein inside the inactivated shell of a weak common cold virus, known as an adenovirus. The Oxford vaccine uses a genetically modified chimpanzee adenovirus that is unable to grow or cause infection in humans (https://www.research.ox.ac.uk/Article/2020-07-19-the-oxford-covid-19-vaccine). This adenovirus has also been modified to possess the Covid-19 spike protein instructions. The resulting (“recombinant”) virus is thus able to enter our cells after injection, allowing our body to make the spike protein and train our immune system in the same way as the mRNA vaccine.
This type of vaccine is harder to fit into the army metaphor. The best I could come up with is to imagine that your army has trained chimpanzees as elite espionage agents, which have infiltrated the enemy and returned to you with intel from the other side. With this crucial information, helpfully delivered by your simian sidekick, you’re ready to fight your no-longer unknown enemy when you come into contact.
Adenovirus vector vaccines take more effort to create than mRNA vaccines, but the methods used to create recombinant viruses have been employed by biologists for many years now, so the process is very streamlined. Since the spike protein instructions are inside a virus ‘shell’, rather than just free-floating mRNA, adenovirus vector vaccines are much more stable than mRNA vaccines, as evidenced by their ability to be stored in a conventional fridge, just like inactivated vaccines (https://biotechscope.com/oxford-universitys-fridge-stored-covid-19-vaccine-is-90-effective/). This makes them much easier to distribute around the world, which combined with their relatively low cost makes adenovirus vector vaccines (the Oxford vaccine in particular) excellent candidates to fight Covid-19 in LEDCs.
Hopefully this vaccine explanation, whilst not as “quick” as its title suggests, was helpful in explaining the different types of vaccine currently being employed to fight Covid-19 throughout the world. These vaccines are our key to returning to normality, and it is imperative that citizens in every country around the world come together (figuratively, not literally!) to receive their vaccinations and hopefully bring an end to this pandemic.
Header image: Verity Laycock