﻿Billions of people worldwide have been vaccinated against COVID-19,
but dozens of research teams are still working on more coronavirus vaccines - why?
In a word: evolution.
The first COVID-19 vaccines protected against SARS CoV-2 the original version of the virus that emerged in 2019.
But as new covid variants evolved the protection provided by the original vaccines did not.
While some immune cells like B cells can mature and develop to some extent the antibodies they
produce after exposure to early vaccines still struggle to latch on to newer variants like Omicron
- and that contributes to a higher risk of infection.
And so researchers are developing a whole host of next generation vaccines
in the endless race to stay one step ahead.
One approach is to update and combine vaccines. Companies like Moderna, Pfizer and BioNtech
have already started to introduce new bivalent mRNA vaccines.
Designed to target both the original version of the virus, and new Omicron variants.
These boosters encode molecules from the original and Omicron spike proteins.
The goal is to retrain existing B cells, as well as stimulate the creation of new B cells
- all in the hopes of producing antibodies that bind more tightly to the newer variants.
Although as of yet it's unclear how much of a difference this will make.
This approach is also being used to create combination vaccines which could protect
against COVID variants as well as other diseases like influenza.
While potentially helpful, updating COVID vaccines in this way will always be a step
or two behind the virus. And so scientists also want to develop ‘broadly protective’ vaccines
that can target future variants – and even related coronaviruses - before they arise.
One way to do this is by creating a vaccine that targets parts of the virus that don’t tend to mutate.
Currently, most COVID-19 vaccines are based on the spike protein,
but several groups are now focussing more specifically on the part
of spike which binds to human cells - the receptor binding domain or RBD.
Now the RBD contains some regions which mutate relatively little between COVID variants and are even
conserved in certain related coronaviruses.
What’s more researchers can pepper vaccine particles with many different RBDs
rom a whole host of COVID variants and close relatives.
This is called a mosaic vaccine.
To train antibody-producing B cells you want them to bind to your vaccine particle
and those that bind more strongly are more likely to replicate and flourish
In the case of this mosaic vaccine, the strength of the binding relates to how many RBDs the B cell can latch on to.
The theory therefore is that B cells that can only latch on to one or two specific RBDs
won’t bind strongly enough to replicate.
But the B cells that flourish will be those that can bind to many RBDs,
and the reason they'll be able to do that is they can recognise the regions that are shared between them.
In effect you end up with an immune response that sees past the variation and focuses on the shared, broad features of these viruses.
Clinical trials are due to start in the next two years.
While spike is the most potent target for B cells, it’s not the only vaccine target for the immune system.
For example, T cells, that destroy infected cells,
can recognise many other viral proteins, and scientists are hoping to create vaccines that
capitalise on this, using proteins such as ORF3a, nucleoproteins or membrane proteins.
This could better mimic a natural infection, only far more safely.
Several of these vaccines are in late stages of trials.
And there’s more. Currently there are 4 different types
of COVID-19 vaccines, known as platforms, which have been approved for use.
But next-generation vaccines could include updates to these designs.
First mRNA.
mRNA vaccines helped turn the tide of the pandemic, particularly in wealthier
countries where the vast majority of doses have been sold.
But a twist on this technology might make vaccines cheaper, more potent and even reduce side effects.
mRNA vaccines contain instructions for our bodies to create a modified version of spike,
packaged in a fatty nanoparticle.
But new generations of mRNA vaccines, might also include instructions for a replicase protein
which can instruct cells to churn out more copies of spike. This means that a smaller dose of these
self-amplifing RNA vaccines could potentially induce the same or an even stronger immune
response whilst simultaneously being cheaper and reducing side effects.
Protein-based vaccines are also in for an update.
Typically, these vaccines are based on single proteins like
spike which stimulates the immune system.
But now, in a new class of vaccine researchers
are building nanoparticles using self assembling proteins which can then be studded with things
like spike or RBD. The mosaic vaccine we discussed earlier is an example of this.
The repetitive arrangement of the viral molecules in these vaccines,
mimics the actual virus, and it’s hoped that it will generate an especially potent response.
And it isn’t just the platforms that could see an overhaul
- new delivery methods are also on the horizon.
For example, nasal vaccines which are inhaled as a mist through the nose or mouth,
or administered as nasal drops.
By prompting an immune response where the
coronavirus enters the body - the thin mucous membranes that line the nose and mouth,
these vaccines could - in theory - stop the virus before it spreads - helping
further interrupt transmission, not to mention being much simpler to administer.
There's a lot of innovation on the horizon.
But in a crowded market, all of these new vaccines face the same key challenge,
and that’s proving they offer genuine improvements over existing jabs.
And that’s not as easy as you might think.
Many of them will try to focus on new selling
points - like further reducing transmission of COVID or treating multiple infections such as COVID and flu.
But with over fifty vaccines already approved and hundreds more actively in
clinical trials new vaccines will really have to stand out to make an impact.