The two vaccines first approved for COVID-19, from Pfizer-BioNTech and Moderna, have several key facts in common. Both are much more effective than anyone had expected. Both were developed in record time. And both use messenger RNA (mRNA), a type of technology that is being used for the first time.
The basic technology of mRNA vaccines has been in development for decades, but the frenzied work on COVID-19, and the ultimate success of those vaccines, has changed the near-term potential. After making such a big impact on its first implementation, it’s possible that mRNA vaccines and treatments may begin to be used for other diseases. “The funding and singular focus on COVID vaccine development that we’ve seen this year has really been extraordinary,” says Jess Atwell, a scientist at the Department of International Health in the Bloomberg School of Public Health. “And that has helped move the field forward.”
The vaccines work by injecting the genetic code for the body’s own cells to make a viral protein, which won’t cause the disease, but causes an immune response, so when someone is later exposed to the virus, they will be protected against it. Traditional vaccines also stimulate an immune response, but require a longer process of growing ingredients in a factory—for example, a virus might be altered so that it can’t make people sick, and then the virus has to be grown in a lab or factory to make the vaccine. Development takes longer. An mRNA vaccine, by contrast, can be made by essentially swapping genetic code in the underlying mRNA platform. In January, when researchers at Moderna and the National Institutes of Health first got the genetic code for the new coronavirus, they finished their new vaccine just days later.
Scientists first tested the underlying concept as long ago as 1990, when studies showed that mice injected with RNA or DNA could produce the proteins that were encoded. But vaccines or other treatments weren’t viable at first; the mRNA degraded quickly after it was injected and could cause an inflammatory response. A later breakthrough modified the technique so it produced more protein and didn’t cause the same negative response. Next, scientists figured out how to make the mRNA last longer by encasing it in tiny bubbles of fat (a “lipid nanoparticle”). Researchers eventually began developing mRNA vaccines for Zika, the flu, and other diseases, overcoming other hurdles through that development. Those other vaccines are still in progress, and nothing had made it through final clinical trials until COVID-19.
In a future pandemic—a scenario that is, unfortunately, likely—scientists could again quickly plug the genetic code of a new virus into the basic mRNA platform. Because mRNA factories now exist, production could also happen much more quickly. “Most manufacturing facilities that are built for vaccines are made to produce one specific vaccine—they’re not adaptable,” says Atwell. “But with this technology, you could theoretically put any sequence of mRNA inside the lipid nanoparticle. The manufacturing capacity can be switched from a vaccine for one pathogen to a vaccine for another much more easily than traditional vaccine manufacturing facilities.”
This type of vaccine could also soon be used for the flu; Moderna had a flu vaccine in early clinical trials before the COVID-19 outbreak began. For the seasonal flu vaccine, which has to be reformulated every year, the new type of vaccine could make it more likely that the vaccine works well. “That process has to start in February in the Northern Hemisphere in order to have vaccine in September or October, and sometimes the strains that are chosen don’t end up being the predominant one circulating that winter,” Atwell says. “So if there was technology where you could wait longer to make that decision, and still have vaccine in time for the season, that could be really helpful in making sure that there was a good match between the circulating strains and the vaccine.”
Cancer vaccines are also in development, not to prevent disease, but to treat existing cancers. In one approach, scientists take the genetic profile of someone’s cancerous cells and healthy cells, use algorithms to compare them, and then create a personalized vaccine designed to help the immune system learn to fight the cancer. “mRNA vaccines have the ability to induce strong T cell responses that can efficiently kill tumor cells,” says Norbert Pardi, a research assistant professor of medicine at the University of Pennsylvania who focuses on mRNA vaccines. “Both companies and academic labs are developing mRNA-based vaccines against cancer, and the early findings are very promising.”
Scientists are also working on mRNA vaccines for rare genetic diseases and for other infectious diseases such as HIV. The process will still take time. “A lot of that depends on our ability to find the right immunologic target—for SARS-CoV-2, we had good information to support that antibodies to the spike protein could be protective, so the mRNA vaccines were made to generate antibodies to the spike protein,” says Atwell. “Our immune response to HIV is complex, which makes the design of a vaccine also complex.”
The success with COVID-19—and other mRNA COVID-19 vaccines that are still in trials, but may soon also be proven to work—may help drive more funding and attention to other mRNA projects and help them move more quickly. “COVID-19 was an opportunity for the field to prove that mRNA vaccines can be quickly developed and they are safe and work very well not only in animal models but also in humans,” Pardi says. “I really hope that the success of SARS-CoV-2 mRNA vaccines will accelerate other mRNA vaccine programs as well and we will have FDA-approved mRNA vaccines against other pathogens in the near future.”