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The Future of mNRA Vaccines
The Future of mRNA Vaccines
These shots hold promise for everything from flu to cancer
by Arlene Weintraub
I
N NOVEMBER 2021, the World Health Organization classified omicron as a new COVID-19 variant of concern, after a team of South African scientists sounded alarm bells about its highly transmissible nature. Just two months later, vaccine maker Moderna started a clinical trial to study the effectiveness of an omicron-specific booster shot.
The new mRNA technology behind the Moderna and Pfizer-BioNTech COVID-19 vaccines is being hailed as a game changer 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.
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 eradicate 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 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.
Moderna is now developing five mRNA vaccines covering four seasonal flu viruses, three of which are in 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, Weissman explains.
Other 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 and co-director of the Harvard University 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.
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 Gandhi: “We’re on the threshold of a new revolution in vaccinology.” l
