The Future of mRNA Vaccines

In December 2020, scientists in South Africa sequenced the genome of a variant of SARS-CoV-2 that was causing an aggressive new strain of COVID-19 to start spreading around the world. Just two months later, vaccine maker Moderna said it was ready to test two booster shots to its original COVID vaccine — both designed to tackle the new variant.

The new mRNA technology behind the Moderna and Pfizer-BioNTech COVID-19 vaccines is being hailed as a gamechanger in the future battle against infectious diseases, and even against some cancers. That’s largely because of how quickly mRNA vaccines can be developed in response to new invaders — and then tweaked if those invaders mutate to try to escape an immune attack. “There are hundreds and hundreds of diseases for which mRNA could be useful,” says Dr. Drew Weissman, a professor of medicine at the University of Pennsylvania whose lab has developed several mRNA vaccines that are on the verge of human testing.

[SEE: 7 Signs Your N95 Mask Is Fake.]

Next up: the Flu

Making an mRNA vaccine entails taking a piece of a virus’s DNA strand — in the case of COVID, it’s the part that makes the spike protein that gives the virus that studded appearance — and using it to teach the immune system to recognize and eliminate the virus. The vaccine causes cells to make the target protein, prompting the immune system to eliminate the virus anytime it appears in the body.

One target for which the technology is considered especially promising: influenza. Manufacturing the seasonal flu vaccine currently is a laborious six-month-or-longer process that involves growing what are predicted to be the dominant virus strains in eggs, harvesting and inactivating them, and then making vaccine doses at a huge scale. If an unexpected strain pops up, the vaccine can’t be changed on a dime to cover it. An mRNA vaccine that teaches the body to recognize hemagglutinin A or B, the proteins on the surface of flu viruses, could be developed much faster and adjusted quickly, Weissman says.

[SEE: 9 Myths and Misconceptions About the Flu Vaccine.]

In January 2021, Moderna said it was developing three mRNA vaccines covering four seasonal flu viruses, and the company has recently begun human testing.

Weissman and a range of companies, including mRNA vaccine developer CureVac, are using the technology to try to develop a universal flu vaccine — a single shot that could cover most strains of the influenza A virus that emerge over time. Rather than target the “head” of the hemagglutinin protein, which tends to mutate every year, the vaccine would be designed to elicit an immune response to the less changeable “stem” or “stalk” region, explains Weissman.

Other Disease Targets

Moderna and BioNTech are also working on mRNA vaccines to prevent HIV, a virus that mutates quickly. The idea is to use the technology to elicit broadly neutralizing antibodies, immune proteins that target the virus and keep it at bay even as it changes, says Dr. Rajesh Gandhi, an infectious diseases physician at Massachusetts General Hospital and co-director of the Harvard Center for AIDS Research.

And mRNA technologies could be applied to develop vaccines against other viruses that can hide out in the body for years, often producing no symptoms but raising the risk of other diseases. Epstein-Barr virus, or EBV, has been linked to an increased risk of multiple sclerosis and some cancers, for example. In February 2020, just before the pandemic diverted the biopharma industry’s attention, Moderna announced it was starting clinical trials of an mRNA vaccine to prevent EBV.

“There is increasing evidence that infectious agents may be a trigger for some of the major diseases of mankind,” says Dr. Anthony Komaroff, a professor of medicine at Harvard Medical School. “A vaccine given early in life could have an enormous protective effect.”

Other diseases for which mRNA vaccines are now in development include Zika, yellow fever and tuberculosis. Therapeutic mRNA vaccines designed to stimulate an immune response to cancer are also being explored in melanoma, prostate cancer, lung cancer and many other tumor types. Says Ghandi: “We’re on the threshold of a new revolution in vaccinology.”

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