One of mRNA’s strengths is its “remarkable agility,” as Hatchett puts it. Its only raw ingredients are the four nucleotides that form the “letters” of the RNA sequence, so it can be designed and made pretty rapidly. “Biological manufacturing is very hard and temperamental and has been difficult to introduce in many environments. It’s taken India decades to build up the vaccine manufacturing capability they have,” says Hatchett. “It may be easier for countries to develop an mRNA production capacity than traditional biological manufacturing capability.”
Developing countries could, Hatchett suggests, leapfrog over traditional vaccine-manufacturing processes and go straight to mRNA—mRNA plants are already being planned in countries across Africa and Asia. After Covid, they could be quickly repurposed to create 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 quickly translates, expresses, and breaks down the strand of mRNA.
“mRNA is completely interchangeable,” says Jackie Miller, senior vice president for infectious diseases at Moderna. “What changes between the different vaccines is the DNA template that we utilize to synthesize the messenger RNA, but across all of our vaccine portfolio, we’re using the same lipid nanoparticle.”
CEPI wants to use that flexibility to create a library of mRNA vaccines against each of the viral families known to cause human disease. This would cost $20 billion to $30 billion, Hatchett estimates, but it would enable a rapid response to any new outbreaks. “The lesson from 2020 is that 326 days [the time from sequencing the genome of SARS-CoV-2 to administering the first doses of a Covid vaccine outside of trials] is terrific, astounding, and not fast enough,” he says. CEPI wants to be in a position to make a vaccine for emerging threats within 100 days. “mRNA is an essential, critical component of our being able to achieve that mission,” Hatchett says.
CEPI’s other goal is to improve access to mRNA vaccines, which still need to be stored and transported at extremely cold temperatures (–80°C for Pfizer/BioNtech, –20°C for Moderna), which makes reaching remote areas challenging. The cold chain requirement and the cost are two reasons the majority of mRNA vaccines have been purchased and administered by higher-income countries. In India, 88 percent of people received the AstraZeneca Covid vaccine, which is based on a different technology, doesn’t need to be kept so cold, and has been made available far more cheaply; in the US the overwhelming majority got mRNA vaccines.
That problem will never go away completely—mRNA is inherently unstable, Karikó says, to the point that vaccine shipments can be ruined by a bumpy road—but there is 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, this is not the most convenient presentation,” Miller says. Although mRNA could eventually be cheaper than traditional vaccine manufacturing, that’s not the case today—and ensuring equitable access could require some technical breakthroughs. Dieffenbach suggests freeze-drying vaccine particles for easier transport and storage as one potential solution—eventually mRNA could be squirted up the nose, inhaled as a powder, or applied using a patch. Self-amplifying RNA, which replicates itself inside the body, could enable lower doses, which could lessen the risk of side effects.