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The first mRNA vaccines approved for use in humans – the Pfizer / BioNTech and Moderna Covid-19 vaccines – are being deployed around the world.
These vaccines deliver mRNA, coated with lipids (fat), into cells. Once inside, your body uses the instructions in mRNA to make advanced SARS-CoV-2 proteins. The immune response protects about 95% of people vaccinated with either vaccine against the development of Covid-19.
These mRNA vaccines have many advantages. They are quick to design, so once the manufacturing platform is in place, mRNA vaccines can be designed to target different viruses or variants very quickly. The manufacture of the vaccine is also completely synthetic and does not rely on living cells like chicken eggs or cultured cell lines. This technology is therefore here to stay.
However, there are still issues that we need to improve upon to help make mRNA vaccines more convenient and affordable for the whole world, not just for the first world countries. Here are four areas that mRNA vaccine researchers are working on.
1. How to make them more stable at higher temperatures
We know that mRNA and its lipid layer are relatively unstable in a refrigerator or at room temperature. This is because RNA is more sensitive than DNA to enzymes in the environment that will degrade it.
To overcome this, researchers are trying to test what happens when different types of additives are included, in the hopes that they will extend the shelf life of vaccines. These additives have already been used in vaccines and include, for example, small amounts of common sugars.
Another approach is to lyophilize powdered mRNA vaccines for storage. The idea is to add water to “make up” the vaccine powder before injection. California-based Arcturus is testing this strategy in a phase 3 clinical trial in Singapore.
CureVac, which is also developing a Covid-19 mRNA vaccine, has overcome some of these challenges. He produced a vaccine that was stable for three months at refrigerator temperature.
2. How to reduce the amount of vaccine in each injection
Current doses of the mRNA vaccine range from 30 micrograms (Pfizer / BioNTech) to 100 micrograms (Moderna). In Phase 1 clinical trials, lower doses of the Pfizer / BioNTech vaccine were also active.
Can we go lower than that? CureVac has developed an mRNA vaccine with a dose of 12 micrograms through a combination of innovations in mRNA sequence and lipid formulations. However, the details remain exclusive.
Self-amplifying mRNA is another approach to reducing vaccine doses. Self-amplifying mRNA is designed to make more copies of itself when delivered into cells. This means that only a small initial dose is needed.
Researchers at Imperial College London and Arcturus are using this method to develop Covid-19 vaccines, although trials have only recently completed phase 1.
Although more research is needed to understand self-amplifying mRNA vaccines, it could reduce costs, as less equipment is required.
3. How to go from two doses to one
Current Covid-19 mRNA vaccines need to be “boosted”. This is where the first injection triggers the immune system, and then a second, three to four weeks later, strengthens the immune response.
It would be much easier if a single hit could give the same efficiency. And if Covid-19 stays with us, in the future we will need to boost the immune response regularly, like with annual flu shots.
In this case, a booster injection once a year will be a one-time injection, rather than the current strategy.
Again, self-amplifying mRNA can be useful. Arcturus has announced encouraging results from a single injection of a self-amplifying mRNA vaccine.
In research involving mice, published online but not yet officially published in a journal, a single injection of a self-amplifying mRNA vaccine showed a robust immune response.
Another approach has been developed by researchers at the Massachusetts Institute of Technology for protein vaccines. This uses polymer microspheres which can release the vaccine into the body on day one and day 21. It could “increase” in a single injection. A similar micro-spherical approach could be used with mRNA vaccines.
4.How to stay ahead of viral variants and prepare boosters
We know that mRNA vaccine technology is well suited to respond rapidly to emerging viral variants. This is because the chemical and physical properties of mRNA remain the same, even with small sequence changes needed to match viral mutants. This means that making mRNA vaccines modified for mutants is quick and easy.
The main obstacle to a varied sequence will be regulatory approval. However, in a recent interview, the United States Food and Drug Administration suggested that mRNA vaccines against the mutated versions might be accepted with a small clinical trial (or no testing for future mutations). We don’t know if Australia’s Therapeutic Goods Administration will take a similar approach.
Archa Fox is Associate Professor and ARC Future Fellow, University of Western Australia. Harry Al-Wassiti is a Bioengineering and Research Fellow at Monash University.
This story first appeared on The Conversation and is reposted with permission. To view the original, Click here.
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