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Pharma companies race to develop mRNA vaccines for influenza

Pfizer-BioNTech and Moderna move ahead with Phase 3 clinical trials

by Shi En Kim
September 22, 2022 | A version of this story appeared in Volume 100, Issue 34

A woman sitting and receiving an injection in her right arm from a nurse.
Credit: Shutterstock
Companies have initiated clinical trials of seasonal flu shots that use mRNA technology.

With its global success battling the COVID-19 pandemic, the mRNA vaccine platform has become a hammer that pharma companies are racing to throw new nails under. One of these nails is influenza, which the World Health Organization estimates infects 1 billion people worldwide every year despite an existing vaccine.

Last week, Pfizer dosed its first participants in Phase 3 clinical trials for its mRNA influenza vaccine. “We are using the same mRNA platform as the one for COVID but encoding an influenza target antigen,” says Pirada Suphaphiphat Allen, vice president of viral vaccines at Pfizer, via email. However, “the responses we get for the [mRNA flu vaccine] may not be exactly the same as [COVID’s].” Contrary to SARS-CoV-2, “humans have lived with influenza for hundreds of years . . . prior infection or vaccination could influence how you respond to a newer flu vaccine,” she writes.

Moderna announced in June that it began Phase 3 trials for its mRNA influenza vaccine. Sanofi, which does not yet have an approved mRNA vaccine, initiated Phase 1 clinical trials last year for an mRNA-based flu vaccine candidate. Both Pfizer’s and Moderna’s vaccines provide protection against four different influenza strains. Sanofi’s targets just one, but the company also has a four-strain version in the works.

mRNA vaccines, which deliver copies of a gene or genes to cells to produce immune-triggering proteins, hold several advantages over the traditional kinds. mRNA production can be rapidly customized and scaled up. On the other hand, traditional influenza vaccines contain weakened or inactivated versions of the disease-causing viruses that are grown en masse in cell or egg cultures. Conventional vaccines require arduous purification steps to isolate the active ingredients from these cultures.

As the COVID-19 pandemic has shown, the speed and scalability of their manufacture make mRNA vaccines powerful tools to wield against outbreak-prone diseases, says Thomas Denny, a professor of medicine and the chief operating officer of the Duke Human Vaccine Institute. “If you’re faced with a flu pandemic … then having the ability to rapidly make an mRNA [vaccine] for the flu may be very beneficial.”

As a target virus mutates, mRNA vaccines can be updated to provide better strain matches just by switching out the mRNA sequence. mRNA technology potentially buys more time for health experts to more accurately determine which strains the vaccines should target, because the vaccines can be developed more rapidly and hence closer to the start of flu season than conventional offerings.

It is unknown how the efficacy of mRNA vaccines will stack up against conventional ones to ward off the flu. Current influenza shots only provide 40-60% protection against infection. A double dose of either Pfizer-BioNTech’s or Moderna’s mRNA vaccines against COVID-19 showed over 90% efficacy in thwarting symptomatic infection from the original SARS-CoV-2 strain. So, experts, including Pfizer’s Suphaphiphat Allen, are hopeful that mRNA vaccines will outperform currently available offerings against influenza.

“mRNA vaccines have been so potent,” says John Cooke, the director of the Center for RNA Therapeutics at Houston Methodist Academic Institute. “Everyone was surprised.”

In addition to its work on influenza, Moderna is developing an mRNA vaccine against the respiratory syncytial virus. Pfizer and BioNTech are exploring shingles as a potential mRNA vaccine target.

Denny says that rather than outright replacement, he hopes that mRNA vaccines can be deployed alongside traditional vaccines. Questions about the durability and efficacy of mRNA vaccines remain, but they are undeniably valuable, he says. “I think [mRNA and conventional vaccines] can be thought of as multiple tools in the toolbox to use at different times.”


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