Will Americans have a suitable COVID-19 vaccine this fall? May be

In a few short months, the weather will turn crisp, the holiday season will draw near, and the coronavirus could begin its third consecutive winter of death and devastation.

This prospect forces federal regulators and their scientific advisers to engage in a high-stakes guessing game.

Q: How should the COVID-19 vaccine change?

Certainly circumstances have changed. Coronavirus strains responsible for 97% of infections today – BA.4, BA.5 and BA.2.12.1 – did not exist in 2021, let alone 2020. However, all vaccines currently available in the US are designed to recognize the version that came out of China in January 2020.

Shots are fired great work. Researchers attribute to them saving 1.9 million lives in the US in their first year of availability, and they continue to provide strong protection against severe illness and death from COVID-19. However, the ubiquitous Omicron subvariants have several mutations in their key spike proteins that make them less recognizable to an immune system primed to fight the 2.5-year-old virus.

Result: Real World study found that protection against three doses of the mRNA vaccine was twice as weak against Omicron as compared to the Delta variant that preceded it. Laboratory studies have also shown that exposure to Omicron causes the immune system of those vaccinated to produce far fewer antibodies.

On top of that, the immunity caused by vaccines and initial boosters has weakened. The Biden administration posted order for 105 million doses for the fall booster campaign with the opportunity to buy millions more.

Determining which prescription should be in those doses to elicit optimal protection – the “composition” of the vaccine – is an exercise in guesswork.

Their task consists of several parts. First, experts need to predict which coronavirus variant or variants will dominate the US at the end of 2022 and into 2023.

They then need to predict whether the modified versions of the core vaccines will be effective and not raise new safety, cost, or timely distribution problems.

Getting timely and accurate information about all of this is “really difficult, and it’s the hardest science.” Dr. Peter Marksthe head of the vaccine division of the U.S. Food and Drug Administration, told the agency’s independent advisers last month.

Marks warned that if the FDA waits too long to act on the meager data available, Americans could have substandard protection when the coronavirus flares up again. But speed comes with risk. If manufacturers release reformulated vaccines without first testing them in full clinical trialsThe FDA needs to be confident that existing surveillance systems can quickly detect any new security issues, he said.

“We are asked, in fact, to get a crystal ball,” he was indignant Dr. Arnold Montowho chairs the FDA’s vaccine advisory committee.

And if health officials make the wrong choice, the pandemic-weary country could lose confidence in a vaccine that we will likely need for years to come.

In many ways, the challenge of updating COVID vaccines is an accelerated version of the dilemma that vaccine experts have faced for decades with regard to the flu vaccine.

Each year, several strains of the insidious influenza virus circle the globe and infect new populations. In the process, the composition of circulating strains changes, as does their genetic composition.

So in the early fall and early spring, the World Health Organization convenes an international panel of vaccine experts to assess what mixture of viruses is likely to be circulating in the next six months. Their findings shape the mix of vaccines offered for the upcoming flu season.

Sometimes their predictions are accurate, but not always. Between 2001 and 2010, annual influenza vaccines protected against circulating influenza B strains. only 50% time. during the 2014-15 flu season. wrong guess about influenza A viruses resulted in 758,000 influenza hospitalizations among older Americans and 148 influenza deaths among children.

The preferred U.S. COVID-19 vaccines—Pfizer’s Comirnaty and BioNTech and Moderna’s Spikevax—have a key advantage over traditional flu vaccines: Their mRNA technology allows composition to change at relative speed. Millions of targeted doses of both vaccines will be available by September or October.

In order to extend booster protection to the widest possible range of variants, it would be ideal to know which of the Omicron subvariants is most genetically different from the original coronavirus strain. The combination of these two factors in one shot would give the vaccine “broadness”, which would make it more likely to protect against the wide range of strains that continue to circulate.

It is easy to assume that since they are very recent, BA.4 and BA.5 (which share the same spike protein) have the least in common with the ancestral strain.

But the young field of genetic epidemiology isn’t so sure. Dr. Kanta Subarrao from the University of Melbourne, which is researching the immune system’s response to emerging viral diseases, said the BA.1 Omicron sub-variant is actually a big exception.

If she could decide which version of the coronavirus to target with the fall accelerator, “I would choose BA.1,” Subarrao said at a recent meeting of FDA advisors.

The agency disagreed. In late June, the FDA asked vaccine manufacturers to produce “bivalent” doses which combine the original vaccine with a vaccine designed to recognize BA.4 and BA.5. To whom it will be recommended is not yet specified.

Dr. Paul Offit, a virologist and immunologist at the University of Pennsylvania, believes both approaches are wrong. In his opinion, the original vaccine and boosters do an excellent job of preventing serious illness and death, and the potential benefits of targeting Omicron are too uncertain to justify the risks of releasing a vaccine without a full clinical trial.

Sure, a bivalent booster vaccine can stimulate the immune system to produce more antibodies than a regular booster vaccine, but that doesn’t necessarily mean that recipients will be better off, Offit said in an interview.

“If I were given the choice to vote ‘no’ or ‘hell no’, I would vote ‘hell no’,” he said.

For Offit and most other vaccine experts, the ideal response to the shape-shifting virus would be to develop a universal vaccine capable of neutralizing whatever variants might come up.

This is the approach that has been the holy grail of influenza research, and despite years of work, it remains insanely elusive.

To counter the evolution of the virus, some scientists have tried to develop vaccines that target an unchanging component—say, a protein that does some housework critical to its survival. Others looked at animals such as llamas and alpacaswhich produce very small antibodies that can adapt to viruses when they change.

More recently, a team led by scientists at the California Institute of Technology has developed a complex vaccine containing fragments of eight betacoronaviruses, including the one that causes COVID-19. When given to mice and monkeys, it trained their immune systems to recognize a wide range of viruses, essentially showing them a miniature family portrait.

The next step is a phase 1 human clinical trial that has established many promising universal vaccine candidates.

“It’s not for lack of money. It’s not due to a lack of desire or effort,” Offit said. “It’s just hard to get universal vaccines to work.”