Commentary: It's still worth funding a better COVID-19 vaccine

CHICAGO: Last week, the United States Food and Drug Administration (FDA)’s vaccine advisory committee paved the way for a simpler, flu-like plan for COVID-19. Everyone, whether they’ve been vaccinated before or not, will get a shot tailored to variants on the virus. And likely, people will get those shots once every autumn.

The panel’s recommendation was unanimous but came after lengthy discussion about the limitations of the strategy. Some worried that the Omicron-specific shots seem to offer little improvement over the original vaccine, while others were concerned that an annual shot was too frequent for some - or not frequent enough for others, especially if a new variant emerges.

But there was the underlying theme that seemed to unite everyone: We need next-generation shots and are doing too little to develop them.

The current vaccines - whether the original mRNA shots or the bivalent boosters - do a great job protecting against the worst outcomes of this virus. They have saved millions of lives and kept many people out of the hospital.

But we are heading into our fourth year of living with COVID-19. It’s past time to move beyond chasing variants and put real resources into developing vaccines that offer longer-term protection, or can transform the disease into a something that most of us don’t even realise we have and are much less likely to transmit.

BETTER COVID-19 VACCINES FOR LONG-TERM SOLUTION

Developing next-generation vaccines won’t be easy. Even if they show promise in the lab, proving that they work in humans presents an immense challenge now that much of the world has moved on from COVID-19.

Funding for big trials has dried up and running those studies has become increasingly difficult. The population now has a mix of immunity from vaccines and infections, and the bar is high - showing a shot is more durable or leads to less transmission is harder to measure than showing it keeps people out of the hospital.

That doesn’t mean newer vaccines aren’t worth the effort. Better shots might motivate more people to take them - so far, only 16 per cent of Americans have gotten the latest bivalent booster.

And anything learned in their pursuit will help us not only in the fight against COVID-19, but in dealing with whatever pathogen comes next.

During last week’s FDA advisory meeting, frustration was palpable that we continue to employ a strategy that relies on chasing variants with updated boosters, ones that we know provide only a modest improvement over earlier shots, and offer a limited window of protection at that.

Taking a flu-like model with the current variant-targeted COVID-19 shots is “essentially a Band-Aid strategy,” says John Moore, a professor of microbiology and immunology at Weill Cornell Medical College. “The only real long-term solution is better vaccines.”

NASAL SPRAYS NEXT?

Among the various next-generation vaccines being pursued, mucosal vaccines, ones typically given as a nasal spray or by mouth, have gotten the most attention.

The concept is tantalising: Train the immune cells in our nasal passages and airways, exactly where the virus enters our body and starts to replicate. These vaccines still won’t completely stop the virus - vaccines rarely achieve what scientists call “sterilising” immunity.

But the hope is a nasal vaccine, perhaps combined with a conventional shot before or after, could lead to more asymptomatic cases and a far lower chance of transmitting the virus to others.

That could matter on both an individual level and a societal one. On a personal level, people who still contracted COVID-19 would not feel so sick, could live without the fear of long COVID, and wouldn’t need to miss things like family weddings. On a broader level, fewer cases would alleviate the pressure on hospitals.

MONEY PROBLEMS

Unfortunately, turning nasal vaccines into reality has a long way to go. The same is true for any newer approach to combatting COVID-19.

Money is a big part of the problem. As one member of the FDA’s advisory committee put it during the meeting, work on vaccines with broader protection needs more urgency and resources, “not slow-paced, back-seat research”, said Pamela McInnes, the former deputy director of the National Institutes of Health’s National Center for Advancing Translational Sciences.

Yet much of the vaccine pipeline is being developed by universities or at small biotech companies. The US government does not have a good track record of translating academic ideas for vaccines into products. Operation Warp Speed was the game-changing exception, but “we’ve reverted now to the pre-pandemic norm” of underfunding vaccine development, Moore says.

Investors, meanwhile, have little appetite for an area they worry won’t result in a commercial market, says Stephanie Langel, an expert in mucosal immunity at Case Western Reserve University’s School of Medicine who has conducted animal studies on an oral COVID-19 vaccine.

Attracting funding is made harder by a murky path to market for next-generation vaccines. Researchers complain that the FDA hasn’t offered a clear framework for running trials for newer shots or nasal sprays.

Those guidelines, if they ever arrive, will likely require companies to show a newer product is as good as or better than the current mRNA shots, but perhaps also demonstrate they offer better variant coverage, are more durable or can prevent transmission. All of that will likely require large, complex trials - ones that might be even more expensive and take far longer to run than the ones that got us the current vaccines.

IMPROVING UNDERSTANDING OF IMMUNE RESPONSE

One thing that could help: A more sophisticated understanding of our immune response to both vaccines and infection. So far, the world has largely focused on levels of neutralising antibodies generated against the virus, a measurement that clinical studies have allowed us to correlate to protection against severe disease.

But researchers have been clamouring for more attention to be paid to other types of immune cells, such as T-cells and other components that might be important for specific types of protection. It could become easier to run vaccine studies if we knew how to correlate those other immune components to, say, asymptomatic disease versus severe disease.

Understanding the details of that immune response will be important and particularly complex for mucosal vaccines. Unlike pulling neutralising antibodies out of a blood draw, capturing the immune response in mucosa is less straightforward.

Among the unknowns: Should immune cells be measured from a nasal swab or spit? What’s the right level of antibodies needed to slow transmission or stop infection? What test should be used to ensure everyone is measuring these cells in the same way?

We might get to this critical understanding faster for all kinds of COVID-19 vaccines if the FDA would encourage - or better yet, require - companies to gather more robust information on immunity so that everyone could learn from it. 

SHORT-SIGHTED TO NOT PURSUE NEW COVID-19 VACCINES

Congress has made clear that it’s not coughing up Operation Warp Speed-level money for this or any other COVID-19-related project. Given the state of the pandemic, that’s not surprising.

But to let these next-generation vaccines die on the vine would be short-sighted. Last week, more than 3,700 people in the US died from COVID-19 - deaths that in part could have been prevented if people were more willing to get vaccinated, or if we could lower transmission in our communities with better shots.

Aspiring for a future with a dramatically lower COVID-19 death rate seems like a worthy investment.