The first mRNA vaccines approved for use in humans – the Pfizer / BioNTech and Moderna Covid-19 vaccines – are being rolled out around the world.
These vaccines deliver mRNA coated with lipid (fat) into cells. Once inside, your body uses instructions in the mRNA to make SARS-CoV-2 spike proteins. The immune response protects about 95% of people vaccinated with either vaccine from developing Covid-19.
Such mRNA vaccines have many advantages. They are quick to design, so once the production platform is set up, mRNA vaccines can be designed to fight different viruses or variants very quickly. Vaccine production is also completely synthetic and does not depend on living cells such as chicken eggs or cultured cell lines. So this technology is here to stay.
However, there are still problems that we need to improve to make mRNA vaccines more practical and affordable for the entire world, not just 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 the lipid layer are relatively unstable in the refrigerator or at room temperature. That’s because RNA is more sensitive than DNA to environmental enzymes that break it down.
To overcome this, researchers are working to test what happens when different types of additives are added, in the hope that they will extend the shelf life of the vaccines. These additives have been used in vaccines before and include, for example, small amounts of common sugars.
Another approach is to freeze-dry mRNA vaccines to a powder for storage. The idea is to add water to “reconstitute” 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 an mRNA Covid-19 vaccine, has overcome some of these challenges. It has produced a vaccine that is stable at refrigerator temperature for three months.
2. How to reduce the amount of vaccine per injection
Current doses of mRNA vaccines range from 30 micrograms (Pfizer / BioNTech) to 100 micrograms (Moderna). Lower doses of the Pfizer / BioNTech vaccine were also active in phase 1 clinical studies.
Can we go lower than this? CureVac has developed a 12 microgram dose mRNA vaccine through a combination of innovations in mRNA sequencing and lipid formulations. However, the details thereof remain the property.
Self-amplifying mRNA is another approach to lower vaccine doses. Self-amplifying mRNA is designed to make more copies of itself once delivered into cells. This means that only a small starting dose is required.
Researchers from Imperial College London and Arcturus are using this method to develop Covid-19 vaccines, although trials have only recently completed the Phase 1 phase.
While more research will be needed to understand self-amplifying mRNA vaccines, it can reduce costs as less material is needed.
3. How to switch from two doses to one
Current Covid-19 mRNA vaccines need a “boost”. This is where the first injection boosts the immune system, and a second, three to four weeks later, boosts the immune response.
It would be much simpler if a single shot could provide the same efficacy. And if Covid-19 stays with us, we’ll need to regularly boost the immune response in the future, like with annual flu vaccines.
In this case, a once a year booster shot is a single injection rather than the current strategy.
Again, self-amplifying mRNA can be helpful. Arcturus announced encouraging results from a single injection of a self-amplifying mRNA vaccine.
In mouse studies, posted online but not yet formally 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 that can deliver the vaccine into the body on day one and day 21. This can give a ‘boost’ in a single injection. A similar microsphere approach could be used with mRNA vaccines.
4. How to stay ahead of viral variants and have boosters ready
We know that mRNA vaccine technology is well suited to respond quickly to emerging viral variants. That’s because the chemical and physical properties of mRNA remain the same even with minor sequence changes needed to match viral mutants. This means that making modified mRNA vaccines for mutants is quick and easy.
The main hurdle to a varied series is regulatory approval. 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 don’t know if the Australian Therapeutic Goods Administration will take a similar approach.
Archa Fox is an Associate Professor and ARC Future Fellow, University of Western Australia. Harry Al-Wassiti is a Bioengineer and Research Fellow, Monash University.
This story first appeared on The Conversation and has been republished with permission. To see the original, click here.