The first mRNA vaccines approved for use in humans – the Pfizer / BioNTech and Moderna Covid-19 vaccines – are being launched worldwide.
These vaccines deliver mRNA, coated in lipids (fat), to cells. Once inside, your body uses the mRNA instructions to make SARS-CoV-2 increase proteins. The immune response protects about 95% of people vaccinated with any of the vaccines against the development of Covid-19.
These mRNA vaccines have many benefits. They are quick to design, so once the manufacturing platform is set up, mRNA vaccines can be designed to target different viruses, or variants, very quickly. The vaccine is also completely synthetic and does not depend on live cells such as chicken eggs or cultured cell lines. So this technology is here to stay.
However, there are still issues that we need to improve to help make mRNA vaccines more practical and accessible to the whole world, not just to first world countries. Here are four areas in which mRNA vaccine researchers are working.
1. How to make them more stable at higher temperatures
We know that mRNA and its lipid coating are relatively unstable in a refrigerator or at room temperature. That’s because RNA is more sensitive than DNA to enzymes in the environment that will degrade it.
To overcome this, researchers are working to test what happens when different types of additives are included, in the hope of extending the vaccines’ lifespan. These additives have already been used in vaccines and include, 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 the 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. It produced a vaccine stable for three months at refrigerator temperature.
2. How to reduce the amount of vaccine with each injection
Current doses of the mRNA vaccine range from 30 micrograms (Pfizer / BioNTech) to 100 micrograms (Modern). In phase 1 clinical trials, lower doses of the Pfizer / BioNTech vaccine were also active.
Can we go any lower than that? CureVac has developed a 12 microgram dose mRNA vaccine through a combination of innovations in the mRNA sequence and lipid formulations. However, the details of this remain proprietary.
Self-amplification of mRNA is another approach to reducing vaccine doses. The self-amplifying mRNA is designed to make more copies of itself, once delivered to 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 tests have recently completed stage 1.
Although more research is needed to understand self-amplifying mRNA vaccines, this could reduce costs, as less material is needed.
3. How to switch from two doses to one
Current Covid-19 mRNA vaccines need “boost”. This is where the first injection prepares the immune system, and the second, three to four weeks later, stimulates the immune response.
It would be much simpler if a single shot could give the same effectiveness. And if Covid-19 stays with us, in the future we will need to increase the immune response regularly, as with annual flu vaccines.
In this case, an annual booster injection will be a single injection, instead of the current strategy.
Again, self-amplifying mRNA can be useful. Arcturus announced encouraging results from a single injection of a self-amplifying mRNA vaccine.
In research involving mice, posted online but not yet formally published in a newspaper, a single injection of a self-amplifying mRNA vaccine showed a robust immune response.
Another approach was developed by researchers at the Massachusetts Institute of Technology for protein vaccines. He uses polymer microspheres that can release the vaccine into the body on day one and on day 21. This could “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 reinforcements ready
We know that mRNA vaccine technology is well suited to respond quickly to emerging viral variants. This is because the chemical and physical properties of the mRNA remain the same, even with small changes in the sequence necessary to match the viral mutants. This means that making modified mRNA vaccines for mutants is quick and simple.
The main obstacle to a varied sequence will be regulatory approval. However, in a recent interview, the US Food and Drug Administration suggested that mRNA vaccines against mutated versions could be accepted with a small clinical trial (or no trial for future mutations). We do not know whether the Australian Therapeutic Products Administration will take a similar approach.
Archa Fox is Associate Professor and ARC Future Fellow, University of Western Australia. Harry Al-Wassiti is a bioengineer and researcher at Monash University.
This story first appeared in The Conversation and is republished with permission. To see the original, Click here.