mRNA-based vaccines need to come out of the freezer

The first The successful attempt to transport vaccines over long distances was crude but ingenious. In 1803, seven years after Edward Jenner demonstrated that inoculations of the lymph from cowpox pustules could protect against smallpox, a group of 22 orphaned boys embarked from La Coruña on a ship bound for the American colonies of Spain. Two were deliberately infected with cowpox. When pustules developed, Francisco Xavier de Balmis y Berenguer, the doctor who had organized the expedition, used the lymph to inoculate two more. And so on, until the ship arrived, just over two months later, and vaccines could be given to residents.

It was a splendid success. Thousands of people across the empire, as far north as Mexico, as far south as Peru, and (after a further expedition across the Pacific) as far west as the Philippines, were vaccinated. Even today, although the use of orphans for them is discouraged, the concept of vaccine preservation chains lives on, with “cold chains” of refrigerators or freezers being routinely employed to preserve heat-sensitive material being moved from one place to another. to another.

But cold chains are not ideal, especially in countries with dubious electricity supplies and a lack of technicians to keep them in perfect condition. Therefore, forms of heat stabilizing vaccines are therefore constantly in demand. And two may be available soon for some of the more heat-sensitive of the lot, omRNA newly developed vaccines against SARSWOV-2, the agent of covid-19.

The Pfizer version of this vaccine is particularly demanding. It should be stored at around -70°C. But even Moderna’s offering requires around -20°C. And the problem will soon increase, because theRNA The approach to vaccine production is being extended to other diseases, including cancers and infections. In January 2022, a transnational group called the Coalition for Epidemic Preparedness Innovations (CEPI), therefore, makes a plea for new ways to preserve and deliver mRNA vaccines. So far, it has received more than 70 proposals, of which two in particular, from companies called 20Med and Vaxxas, look promising.

Messenger RNA Vaccines, to give the full name, have a couple of components, both of which are sensitive to heat. The first, ohRNA itself is a form of genetic material that encodes a piece of viral protein. When produced by subcellular factories called ribosomes, which translate the RNAPost, this protein fragment trains the immune system to recognize and fight the virus. The other component is an oily layer of lipid nanoparticles (LNPs) where the RNA it’s packaged for protection until it reaches its target, but still allows it to be exposed to cells in a way that triggers an immune response.

The approach developed by 20Med improves the protective shield, without compromising the content’s ability to trigger immunity, by replacing the LNPs with proprietary polymers of composition not yet disclosed. These preserve the RNA from degradation to reaching its destination. This version still requires cooling, but not below freezing. Something between 2°C and 8°C is fine, so all you need is a standard fridge.

Vaxxas’ approach is more radical. Its researchers are developing a dry vaccine delivered by skin patches armed with thousands of tiny needles. When a patch is applied, needles penetrate the surface and deliver the vaccine to the immune cell-rich layers below.

A piece of good luck

The point of doing this is that removing water from a vaccine stabilizes it. The main factor drivingRNA the degradation in storage is hydrolysis – the breaking by water of the chemical bonds that hold a molecule together. Even a change in a m threadRNA can prevent it from working properly. Less water means less hydrolysis, and that means less damage.

The resulting product stability means that patches can be distributed by mail instead of using a special courier or delivery company. They can also be stored for use in future outbreaks. And there is one more benefit. Using patches in this way eliminates the need to train people to administer doses by injection, as applying a patch is easy.

Both new approaches are still in the early stages of development. But Richard Hatchett, CEPIhead of, rate mRNAVaccine-based vaccines will be “an important part of our arsenal to prepare for future emerging diseases.” The ability to develop, manufacture and distribute effective vaccines will be vital. Xavier de Balmis would have been proud.

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