Universal flu vaccine may be next big Moderna, Pfizer mRNA development

The research and development that led to the Covid-19 vaccines have boosted efforts to find a more powerful, longer-lasting flu vaccine, perhaps taking steps towards virologists’ holy grail: a one-time, universal flu jab.

Scientists at Pfizer and Moderna, the pharmaceutical companies that harnessed a half-century of research into mRNA technology to create Covid vaccines, are using that same know-how in exploring ways to inoculate the masses from the flu.

“As demonstrated through the COVID-19 vaccine, mRNA vaccines offer…the potential to manufacture higher potency flu vaccines more rapidly than contemporary flu vaccines,” Pirada Suphaphiphat, vice president of viral vaccine research at New York City-based Pfizer, told CNBC by email. “The pandemic allowed us to deliver on the immense scientific opportunity of mRNA.”

In 2020, the number of flu cases was down precipitously, mostly likely due to Covid restrictions. But as this winter sets in, influenza infections and hospitalizations continue to rise, especially in eastern and central states, according to the weekly Centers for Disease Control and Prevention Fluview report.

The CDC always recommends the annual flu vaccine as the best way to protect against contracting the virus and its potentially serious complications. There have been signs, however, that flu vaccination rates are lower this season compared to last, which may be attributable to the vaccine hesitancy that has erupted during the coronavirus pandemic.

Although one flu virus usually dominates each year in North America — the A(H3N2) this season — quadrivalent jabs are designed to protect against three other strains that may cause infections as the virus mutates from month to month.

This shotgun approach acknowledges the fact that flu vaccines are only 40% to 60% effective in preventing infection, and sometimes by a flu season’s end only 10% effective. Conventional flu vaccines are grown in either chicken eggs or mammalian cells and also takes about six months to produce the millions of doses needed.

Conversely, mRNA-based influenza vaccine design requires only the genetic sequence of the dominant virus, which significantly accelerates production time. The flexibility of mRNA technology and its rapid manufacturing time, Pfizer reports, could potentially allow better strain match, greater reliability of supply, and the potential opportunity to improve upon the efficacy of current flu vaccines.

 “We think mRNA is the ideal technology to take on this challenge,” Suphaphiphat adds.

The technology behind messenger RNA, or mRNA, has been in development since it was discovered in 1960, but the Pfizer and Moderna Covid vaccines marked the first time it had been approved for use in humans.

It’s now being applied to the development of several different vaccines. Pfizer and Germany’s BioNTech said earlier this month that they will develop a potential mRNA-based vaccine for the prevention of shingles, while scientists have said they are hopeful the technology could be a turning point in the development of a HIV vaccine.

“mRNA is a platform,” Moderna CEO Stéphane Bancel said of broader vaccine ambitions on CNBC’s Squawk Box on Monday. “mRNA is an information molecule and so we have now forty-four zero programs that are in development and actually many more in the labs.”

With a focus on respiratory disease, Bancel said there are around 10 viruses that lead to hospitalizations every year.

“Flu, of course, is very well known but RSV, and many other viruses that are not very well known to the public because the symptoms are similar to flu where we believe the world deserves the single annual booster that contains all those different vaccines in a single dose against flu, against RSV, against Covid with the right adaptation to the strains circulating that’s here, and that’s what we’re working towards,” he said.

Moderna has a RSV program and a flu program in trials and “we’re working very quickly to combine this,” Bancel said.

“The way I think about it, it’s a bit like you’ll get an annual upgrade of a product by adding more vaccine in the same vial. So, you’ll get an adaptation for the current strains of that year in your geography, so in the U.S., or in Europe, or in Japan because as we see a lot of winters, the flu vaccine are perceived not to work because we are actually different strains circulating around the world.”

In September, Pfizer announced the beginning of a phase 1 human trial of an mRNA flu vaccine for adults, marking the drug maker’s first mRNA-based flu program. It is a so-called quadrivalent vaccine, like those administered to the public today, targeting four different flu variants.

In December, Moderna announced the first positive interim data from a phase 1 study of its quadrivalent seasonal flu vaccine candidate, called mRNA-1010, in older and younger adults. The company also announced that the phase 2 study of mRNA-1010 is now fully enrolled, and preparation for the phase 3 study is underway.

While generally encouraging, the findings nonetheless showed that Moderna’s mRNA-based flu vaccine was no more efficacious in older adults than already-approved shots on the market, in particular Sanofi’s Fluzone HD. After Moderna’s investor presentation of the findings, its shares dropped 10%. “We can’t make a direct comparison. We presented (Fluzone data) only as guidance,” a company executive said on a conference call with investors and urging them to wait for further data before selling off shares.

Typically, Big Pharma companies such as Pfizer and Moderna shy away from early-stage R&D on flu vaccines, because historically they generate modest revenues. The global influenza vaccine market was estimated at $6.59 billion in 2021 by Fortune Business Insights and is projected to grow to $10.73 billion in 2028 at a CAGR of 7.2% during that forecast period. Worldwide revenues for the entire pharmaceutical industry were $1.27 trillion in 2020, according to Statista.

However, covid vaccines are another story altogether.

In November, while reporting its third-quarter earnings, Pfizer said it expects its coronavirus vaccine to bring in $36 billion in revenue in 2021. Around the same time, Moderna lowered its 2021 Covid vaccine earnings projections to between $15 billion and $18 billion, down from an earlier estimate of $20 billion, partly due to production problems.

With Covid-related deaths in the U.S. at more than 832,000 and more than 5.4 million worldwide, the public has taken its eye off the seasonal flu, which runs from October to May. Yet it has its own deadly history, with four flu pandemics occurring in the past century (1918, 1957, 1968, 2009), taking at least a million lives during each.

From 2010 to 2020, the CDC estimates that the flu caused between 12,000 and 52,000 deaths in the U.S. annually, from among nine million to 41 million infections. Globally, the World Health Organization (WHO) estimates that the flu kills 290,000 to 650,000 people every year.

Despite those horrific statistics, R&D toward improved flu vaccines, as well as funding, has been relatively paltry and largely confined to academia, biotech startups, and the National Institutes of Health (NIH).

The NIH’s National Institute of Allergy and Infectious Diseases (NIAID) unit has an annual budget of about $220 million for the universal flu vaccine, a chunk of it dispersed as grants to the Collaborative Influenza Vaccine Innovation Centers, or CIVICs, launched in 2019. By comparison, the NIH earmarked nearly $7 billion for researching cancer, which claimed 606,520 lives in 2020.

Last November, Connecticut Rep. Rosa DeLauro and Massachusetts Sen. Ed Markey reintroduced the Flu Vaccine Act, a bill proposing an investment of $1 billion for the NIH’s flu research projects, including external collaborations.

There are dozens of other flu vaccine R&D projects underway in the U.S., some in search of what are known as supra-seasonal shots that could prevent recipients from becoming infected for several years. A promising program is underway at the University of Washington’s Medicine Institute for Protein Design in Seattle by a team led by Neil King, an assistant professor of biochemistry at the university’s School of Medicine, using computers to design new, self-assembling protein nanoparticles to produce a vaccine.

“The vaccine is in a small phase 1 trial at the NIH,” King said. “Volunteers have been dosed and we’re starting analysis.” He anticipates having results in a couple of months, and following phase 2 and 3 trials, receiving FDA approval “within the next five years.”

NIAID is involved in several universal flu vaccine phase 1 trials, said Dr. Jennifer Gordon, program officer, influenza vaccine development. One launched in 2019 and another last June, each employing different scientific approaches.

Without pinpointing a timeframe, Dr. Gordon is hopeful that a truly one-time flu vaccine will someday become a reality but doesn’t overlook creating better ones in the meantime. “We don’t want to say we only care about vaccines that last forever,” she said. “There are approaches that are significant improvements over what we now have and are huge wins, even if not they’re not universal.” 

Pfizer CEO Albert Bourla said on Monday that its recent research collaborations will enable it to target the flu, specifically, through DNA technology that allows it to reduce the time it takes to produce an essential part of the overall manufacturing process for RNA vaccines from almost a month to a couple of days.

“That could cut dramatically, potentially even further our ability to have new variant vaccines if needed, instead of three months into two. That will produce let’s say dramatic benefits for, for our fighting against Covid and other diseases like flu, for example, because that will allow you to be very, very close the time that the new variants are circulated,” Bourla said.