Scientists fear the omicron shots coming this fall won't be much better at keeping people from getting COVID-19 than what's come before. That's pushing drugmakers to start working on next-generation vaccines that don't have to be updated that often, if at all.
Testing shows that omicron-specific vaccines under development at Moderna Inc. and the partnership of Pfizer Inc. and BioNTech SE will be "little or no better" than the currently available boosters, according to John Moore, a professor of microbiology and immunology at Weill Cornell Medical College.
"The benefit of switching composition is barely detectable," Moore said.
Both Moderna and Pfizer said their omicron-specific vaccines raised more antibodies to the BA.4 and BA.5 omicron subvariants than current formulations. But the concern remains that the virus is changing so quickly, boosters simply can't keep up. Today's dominant variants may have been replaced by new strains come late September when the new shots are ready, said Greg Poland, head of the Mayo Clinic's vaccine research group. The US needs to focus efforts on next-generation vaccine technology to give more durable protection, said Anthony Fauci, President Joe Biden's chief medical adviser.
"Even with the highly flexible platform of mRNA, which is more flexible than virtually anything we've had before, it's going to be very difficult to keep up with the pace of newly evolving variants,"
Pfizer's leaders had earlier suggested that they weren't focusing on development of an all-encompassing shot. But laboratory evidence has raised the stakes. In June, Pfizer and BioNTech research showed their bivalent omicron-adapted vaccine candidates neutralized BA.4 and BA.5, though to a lesser extent than the original omicron variant, BA.1, prompting the Biden administration to ask for shots that were focused on the newer subvariants.
The original vaccines remain protective against severe disease and hospitalization. But as new variants continue to emerge, the shots, which are based on genetic material from the original strain that spread from China's Wuhan province, have become less effective at preventing infections because they're so different from the variants currently circulating.
"We're pretty much screwed," Poland said, unless drugmakers come up with shots offering stronger protection.
Concern about vaccine durability came up in an April meeting of US health advisers who were debating whether continuous boosting with the currently available vaccines was a suitable strategy. While vaccines are highly effective against severe illness, hospitalization and death, they expressed concern that the virus will continue to mutate in people who get infected.
"We should be thinking about how to make a better vaccine," Lynn Bahta, a panelist and an official with the Minnesota Department of Health, said. "We need to use our expertise to advocate for something that's better, or something that can really resolve the ill effects of disease whether it's mild or severe."
Moderna said it's developing a next-generation COVID vaccine that potentially delivers higher potency, longer durability and enhanced shelf-life. The vaccine is already in clinical trials, the company said in an email.
Pfizer is aiming to use new technology to extend the durability of protection against severe COVID and new variants, Chief Scientific Officer Mikael Dolsten told Bloomberg in an interview. The company's aim is to use closely guarded tech, referred to as its "secret sauce" by Chief Executive Officer Albert Bourla, to confer a full year of protection.
Waning immunity from the shot is "the No. 1 thing we're trying to fix," Bourla said. The company expects to have "broader coverage in terms of variants."
At the end of July, Pfizer and BioNTech started trials of new shots that fight multiple strains at once. This is the beginning of the new strategy to generate longer-lasting immune responses.
While details are scant, the new shots contain two major changes. One is a refined, optimized approach to making copies of the spike protein that the coronavirus uses to enter cells. The vaccine induces cells to make this protein - which is where vaccine-avoiding mutations usually occur - to protect against real infections.
Pfizer's also working on enhancing the response of immune T-cells that are important for protecting against severe COVID cases. Dolsten was guarded in describing the change, saying only that "it will have more components."
In addition, Bourla said, the company is trying to cut the time needed to develop new versions of the vaccine to two months from three.
But that urgency needs to be matched by regulators at the Food and Drug Administration. As the world grappled with mounting death tolls at the beginning of the pandemic, then-President Donald Trump's Operation Warp Speed kicked into gear, bolstering public-private partnerships to make sure a vaccine was created as soon as possible. Today, the FDA is back to moving at its typical glacial pace, said Moore, the Weill Cornell Medical College immunologist.
"We need updated processes like the ones that allowed systems to work quickly," he said.
The FDA is encouraging scientists, the National Institutes of Health, and vaccine manufacturers to develop vaccines that will work across the spectrum of coronavirus versions, Commissioner Robert Califf said late last month in a press call, but those efforts will likely require additional federal funding.
"It's totally within the realm of possibility scientifically that better vaccines can be developed," he said. "It's just going to take time."
Fauci, who also heads the NIH's National Institute of Allergy and Infectious Diseases, said the agency is funding a few different approaches to create a pan-coronavirus vaccine as well as conducting studies looking at preventives that prepare vulnerable tissues to fight infection. For example, the agency is funding efforts to boost protection in the nasal mucosa, where COVID often takes root.
For now, the shots on the market do offer substantial protection against severe disease and hospitalization, and booster shots have an added benefit for people who are older and have weakened immune systems. A study published in July in The Lancet Regional Health medical journal suggested that people 80 and over in Sweden received 71% additional protection against death in the first two months after four doses of vaccine, compared with those who had received three doses. Protection against death declined to 54% in the weeks after that.
The BA.4 and BA.5 shots coming this fall are "the best that we can do under the circumstances," Fauci said. While they may be less effective at preventing infections, they still do keep people out of the hospital, he said.
"The general public absolutely should keep up-to-date in their boosters," Fauci said. "The data are striking "- hospitalizations and deaths are very heavily weighted towards people who are unvaccinated or are not boosted, particularly if you're an elderly person."