The first human-approved mRNA vaccines – the Pfizer / BioNTech and Moderna Covid-19 vaccines – are being rolled out worldwide.
These vaccines produce mRNA, coated with lipid (fat), in cells. Once inside, your body uses instructions in the mRNA to make SARS-CoV-2 proteins. The immune response protects about 95% of people who are vaccinated with any vaccine against the development of Covid-19.
Such mRNA vaccines have many benefits. It’s quick to design, and once the manufacturing platform is set up, mRNA vaccines can be designed to focus quickly on different viruses or variants. The production of vaccines is also completely synthetic and is not dependent on living cells such as chicken eggs or cultured cell lines. So this technology is here to stay.
However, there are still issues we need to improve on to make mRNA vaccines more practical and affordable for the whole world, not just first world countries. Here are four areas that mRNA vaccine researchers are working on.
1. How to make it 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 break it down.
To overcome this, researchers are testing what happens when different types of additives are included, in the hope that it will extend the shelf life of the vaccines. These additives have been used in vaccines before and contain, for example, small amounts of common sugars.
Another approach is to freeze mRNA vaccines in a powder for storage. The idea is to add water to “reconstitute” the vaccine powder before injection. The American company Arcturus is testing this strategy in a phase-3 clinical trial in Singapore.
CureVac, which is also developing an mRNA Covid-19 vaccine, has overcome some of these challenges. It produces a vaccine that is stable at refrigerator temperature for three months.
2. How to reduce the amount of vaccine per shot
Current doses for 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 at a dose of 12 micrograms through a combination of innovations in mRNA sequencing and lipid formulations. However, the details of this remain unique.
Self-amplifying mRNA is another approach to reduce vaccine doses. Self-amplifying mRNA is designed to make more copies of itself once delivered into cells. This means that only a small initial dose is needed.
Researchers from Imperial College London and Arcturus are using this method to develop Covid-19 vaccines, although the Phase 1 phase has only recently been completed.
Although more research will be needed to understand self-amplifying mRNA vaccines, this may reduce costs as less material is needed.
3. How to switch from two doses to one
Current mRNA Covid-19 vaccines need to be “amplified”. This is where the immune system injects for the first time, and then a second, three to four weeks later, boosts the immune response.
It will be much simpler if a single shot can deliver the same effectiveness. And if Covid-19 stays with us, we will need to regularly boost the immune response in the future, as with annual flu vaccines.
In this case, a boost-shot once a year would be a single 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 on mice posted online but not yet formally published in a journal, a single injection of a self-amplifying mRNA vaccine showed a strong immune response.
Another approach was developed by researchers at the Massachusetts Institute of Technology for Protein Vaccines. It uses microsphere polymer that can release the vaccine into the body on the first day and day 21. It can ‘strengthen’ in a single injection. A similar micro-sphere approach can be used with mRNA vaccines.
4. How to present viral variants and have boosters ready
We know that mRNA vaccine technology is capable of responding 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 fit viral mutants. This means that making modified mRNA vaccines for mutants is quick and easy.
The main obstacle to a diverse range is the adoption of regulations. However, in a recent interview, the U.S. Food and Drug Administration suggested that mRNA vaccines against mutated versions could be accepted with a small clinical trial (or no trials for future mutations). We do not know whether the Australian Administration for Therapeutic Goods will follow a similar approach.
Archa Fox is an Associate Professor and ARC Future Fellow, University of Western Australia. Harry Al-Wassiti is a bio-engineer and research fellow at Monash University.
This story first appeared on The Conversation and was published with permission. To see the original, click here.