Many people remember the COVID-19 vaccines, whose fragility made it necessary to maintain a strict cold chain between their departure from manufacturing lines and injection.
This constraint could change: experimental RNA vaccines have proven far more resistant. They retained their properties for up to a year at room temperature thanks to a formulation identified with the help of artificial intelligence.
COVID-19 vaccines.
Pixabay illustration.
Messenger RNA is a fragile molecule. In these vaccines, it is enclosed in tiny fatty envelopes called lipid nanoparticles, which protect it and help it enter cells. Despite this protection, formulations generally need to remain cold. MIT researchers sought to make compositions similar to those used against COVID-19 much more resistant to heat.
Their method acts on the ingredients added around these nanoparticles. Sugars, salts, or polymers can protect the preparation during storage. However, the possible combinations are numerous, and testing them one by one would require many experiments. The team therefore used an algorithm capable of learning from a small number of measurements and then choosing the most promising formulations for further testing.
Concretely, nearly 50 substances already approved as excipients were first examined. An excipient is an ingredient that accompanies the active substance without itself being the vaccine. The algorithm then guided successive trials. According to the study published in Nature Biotechnology, six optimization cycles completed in less than a month were enough to obtain markedly more stable formulations.
The researchers worked with two types of nanoparticles similar to the compositions used for Moderna and Pfizer-BioNTech vaccines. In solid, water-free form, some preparations retained all their biological activity for more than two months at 37 °C. Other trials reported by MIT show stability lasting up to a year at room temperature.
Chemical stability alone is not enough, however: the vaccine must still trigger the expected immune response. In mice receiving an experimental COVID-19 vaccine after prolonged storage, this response remained comparable to that obtained with a fresh preparation. The study also reports immune responses in rodents and nonhuman primates with the thermostable solid formulations.
This heat resistance could reduce dependence on the cold chain. Today, low-temperature storage complicates transport to regions with limited refrigeration equipment. A solid preparation also opens the way to other methods of administration, including patches covered with hundreds of microneedles that dissolve in the skin.
These results remain preclinical: they do not yet demonstrate that a vaccine formulated in this way can be distributed and used in humans for a year without refrigeration. Researchers now have a method for adapting the formulation to different nanoparticles and different RNAs. Additional trials will need to establish the shelf lives and usage conditions suitable for future products.