How do you create a vaccine to fight a new disease?
And why does it take so long?
Well, first you have to identify the virus or bacterium that causes the disease.
In some cases, the pathogen itself can then be weakened or deactivated and used to make a vaccine.
But this isn’t always possible.
In these cases, the next step is to identify the pathogens’ antigens:
unique protein or glycoprotein markers which can form the basis of a new vaccine.
For some pathogens, these antigens always stay the same.
Other pathogens, like the virus that causes flu, can change or mutate their antigens
and so these must be re-analysed every year
Once you have identified the pathogen or antigens, you need to decide how you are going to use
them to build a vaccine. This is called the vaccine platform.
There are a lot of options here, like subunit vaccines that only use part of the pathogen.
There are also newer or more experimental technologies like viral vector
or nucleic acid based vaccines, but we’ll get to these a bit later.
You also need to decide how the vaccine will be administered:
By injection into the skin or muscle,
orally like the polio vaccine,
or through the nose like some flu vaccines.
Each of these options could affect the response the vaccine induces.
For now, let’s say you've decided on the platform and designed the vaccine
- next it needs to be tested
- first in cell cultures and then in animal models.
This might include challenge studies,
where animals that have been given the vaccine are deliberately exposed
to the target disease to see if the vaccine protects them.
Further down the line and If the disease isn’t too serious or effective treatments are available,
humans might take part in challenge studies too.
Once the vaccine candidate is proven safe in animals,
you need to prove you can manufacture it to a high enough standard for people and at scale.
This is called GMP certification.
If the vaccine passes all of these stages it's time to begin human trials.
Normally these come in three phases and they all have to be passed.
First the vaccine is given to a small group of healthy people to test for adverse reactions
- this is called the safety trial.
Second you give the vaccine to hundreds of people,
to work out what dose is needed to trigger a big enough immune response.
Finally you can trial the vaccine in thousands of people, to see how effective it is.
This step is often the slowest and participants are sometimes recruited around the world.
Researchers have to wait for participants to come into contact with the pathogen naturally.
By tracking how many become infected, they can work out how effective the vaccine is at protecting the group.
It can take decades to gather enough data to be sure.
But if you do, the vaccine can finally be licensed.
There are still problems to overcome, however.
Mass producing a vaccine to a high standard can be a difficult job
And once you’ve cracked production, you still have to deliver the vaccine to where it’s needed.
And then there’s Phase IV monitoring - keeping track of rare adverse reactions that the vaccine
might cause even though it's passed the previous trials.
This trial process is very safe, but that comes at a cost - it is also very slow.
In an emergency there are ways to speed things up.
Like reducing the time spent waiting for paperwork to be completed.
Or running different trial phases at the same time. But steps are never missed out.
By working more efficiently, a protective vaccine could be produced in as little as twelve to eighteen months.
And advances in biotechnology could speed up production pipelines as well.
And there are more ways we could speed up production
- let’s come back to some of those newer vaccine platforms.
Nucleic acid vaccines don’t use pathogens or antigens directly.
Instead they deliver the genetic templates for the antigens.
These DNA or RNA templates can be delivered directly
or in lipid nanoparticles that help them to enter cells and improve their stability after injection.
These nano-scale fat droplets encapsulate the RNA or DNA, protecting it as it enters the body.
Some lipid nanoparticles can also act as adjuvants,
molecular triggers to kick start the immune response.
Once inside the body, these DNA or RNA templates instruct
our cells to start making antigens which activate the immune response needed to build immunity.
RNA and DNA are much easier and faster to produce in the lab than antigens are.
They are also potentially safer than vaccines that contain whole pathogens.
That means they could hopefully be used by people with weakened immune systems.
But nucleic acid vaccines are still experimental.
Another approach is called a viral vector.
Viral vector vaccines work by inserting an incomplete segment of genetic material from a pathogen
inside a harmless virus that doesn’t cause disease. This then acts as a vehicle for the genetic material,
delivering it to the right place in the body where it can be translated into proteins,
triggering the immune system.
The viral vector may even be self replicating, increasing the amount of vaccine in the body.
Viral vector vaccines are also quick to produce. Safe vectors have already been established,
and it is relatively easy to insert different target genetic material
into these established carriers.
And as the genetic material inserted is incomplete they can’t replicate and cause disease,
so they are also very safe.
But there is only so much the process can be sped along.
Effective vaccines can save millions of lives,
but before they are used, they have to be proven to be safe and effective.
In the future, researchers hope to develop vaccines against non-infectious diseases
like cancers - based on chemical markers called tumour neoantigens.
Vaccine technology is developing every day and it has a bright future, albeit - a slow and methodical one.