One of mRNA’s strengths, as Hatchett puts it, is its “remarkable agility.” Its only raw materials are the four amino acid bases that make up the “letters” of the RNA sequence, so it can be designed and manufactured very quickly. “Biomanufacturing is very difficult and moody and difficult to introduce in many settings. It took India decades to build up the vaccine manufacturing capabilities they have,” Hatchett said. “It may be easier for countries to develop mRNA production capabilities than traditional biomanufacturing capabilities.”
Hatchett suggested that developing countries could skip the traditional vaccine-manufacturing process and go straight to mRNA production — countries in Africa and Asia are already planning mRNA factories. After Covid, they can be quickly repurposed to make vaccines for other diseases – all you need to do is change the order of the bases in the mRNA to give the body a new set of instructions. There are also far fewer concerns about purity or contamination than with traditional vaccines—the body can rapidly translate, express and break down mRNA strands.
“mRNA is completely interchangeable,” said Jackie Miller, Senior Vice President of Infectious Diseases at Moderna. “The variation between vaccines is the DNA template we use to synthesize messenger RNA, but in all of our vaccine combinations, we’re using the same lipid nanoparticles.”
CEPI hopes to use this flexibility to create a library of mRNA vaccines against every virus family known to cause disease in humans. Hatchet estimates it will cost $20 billion to $30 billion, but it will enable a rapid response to any new outbreaks. “The lesson of 2020 is 326 days [the time from sequencing the genome of SARS-CoV-2 to administering the first doses of a Covid vaccine outside of trials] It’s amazing, it’s shocking, and it’s not fast enough,” he said. CEPI hopes to be able to create vaccines for emerging threats within 100 days. “mRNA is an important part of our mission,” Hatchett said.
Another goal of CEPI is to improve access to mRNA vaccines, which still need to be stored and transported in extremely cold temperatures (–80°C for Pfizer/BioNtech, –20°C for Moderna), making reaching remote areas challenging sex. Cold chain requirements and costs are two reasons why most mRNA vaccines are purchased and administered by high-income countries. In India, 88% of people got the AstraZeneca Covid vaccine, which is based on a different technology, doesn’t need to be kept so cold, and is much cheaper; in the US, the vast majority of people get the mRNA vaccine.
The problem will never go away entirely — Carrico says mRNA is inherently unstable to the point that vaccine shipments can be ruined by bumpy roads — but there’s a trade-off between temperature and shelf life. You can store vaccines at less extreme temperatures, but they will degrade faster. “In some parts of the world, it’s not the most convenient way to show,” Miller said. While mRNA may eventually be cheaper to manufacture than traditional vaccines, that is not the case today – ensuring equitable access may require some technological breakthroughs. Dieffenbach suggested freeze-dried vaccine particles as a potential solution for easier shipping and storage—the final mRNA could be sprayed into the nose, inhaled as a powder, or applied using a patch. Self-amplifying RNA replicates itself in the body, allowing for lower doses, which reduces the risk of side effects.