Updated Covid-19 boosters are expected in September

(CNN) - This fall, Americans could get boosted with a mRNA Covid-19 vaccine unlike any that's come before.

Both Pfizer and Moderna are working on bivalent boosters: vaccines made up of both the old formula and a new one that targets the Omicron BA.4 and BA.5 subvariants of the coronavirus.

If the shots meet US Food and Drug Administration standards, they will probably be available as early as September, the FDA says.

But cases are high now. There are about 124,000 new cases reported each day -- far from the levels reported during the Omicron surge, but nearing peak case rates from the Delta wave -- and cases are more undercounted than ever.

Some experts wonder whether the Omicron-specific boosters will come in time to make a difference and if they will actually offer more protection than the current shots.

A prediction game

The current shots are based on the original strain of the virus and offered nearly full protection, even from infection, early on.

With new variants in circulation, the vaccines still are good at keeping people out of the hospital, but most scientists think people need a vaccine that offers more protection.

Dr. Michael Chang, a pediatric infectious disease specialist at Memorial Hermann Health System in Houston, thinks vaccines with an Omicron component will be helpful -- within limits.

"I just wish that the timing had been sooner so that we could actually be dealing with the kind of BA.5 surge that we have right now," he said.

With the highly contagious BA.5 subvariant now dominant, the goal of minimizing the number of infections is "kind of lost," but the new vaccines should help keep hospitalizations and deaths down, Chang said.

"I do think, anytime you can introduce additional strains or variants into a vaccine, the human body's immune response tends to be a little bit broader and more durable and potentially longer-lasting," he said.

But it's impossible to know at this point what variant will be dominant a couple months from now, how different it will be from the currently circulating variants or even how many cases there will be, because it's hard to predict how humans will behave when cases rise -- and cases will most likely rise.

Much like with the flu, scientists think the coronavirus transmits more efficiently in colder weather. It also spreads more easily as people spend more time indoors.

Dr. Edward Michelson, chair of the Department of Emergency Medicine at Texas Tech University Health Sciences Center in El Paso, is seeing many patients again, even those who had Omicron earlier in the year.

"Omicron is not protecting people even a few months after they got sick with it. These subvariants are getting them again, much to my surprise," Michelson said. "The good news is, most of the patients don't need hospitalization."

Still, 375 people are dying of Covid-related causes on average every day in the US, according to the CDC.

'A new vaccine could really pay dividends'

The Covid-19 Scenario Modeling Hub, a group of scientists across the country who create projections for the coming year, predicts an upswing in hospitalizations through early fall.

But the model suggests that a booster campaign will make a dent in these numbers, according to Justin Lessler, a University of North Carolina epidemiologist who works with the group.

While scientists are still trying to determine exactly how well the new vaccines will protect people, Lessler said, the model assumes that the reformulated vaccine would have about 80% efficacy against infection with the currently circulating strains.

But that depends on how many people actually get an updated booster.

"Absent any real new variants, that kind of efficacy would be enough to really tamp down the current circulation if we have a broad uptake of the vaccines," Lessler said. "A new vaccine could really pay dividends, particularly if we can get it to a broad swath of the population."

Ideally, public health campaigns could be built to encourage people to get a flu vaccine and a Covid-19 vaccine at the same time, he said.

Lessler presented an earlier version of the model to the FDA's independent vaccine advisers, who voted in June to recommend that the vaccine makers include BA.4 and BA.5 in the fall booster.

They said that including an Omicron element would offer more protection.

"While it's impossible for anyone to predict which variants will be circulating at the time, the goal as I see it is to add the subvariants that are most likely to give us that broad spectrum of antibodies that will hopefully prevent serious disease, which is really what we're trying to do," said Dr. Archana Chatterjee, dean of the Chicago Medical School at Rosalind Franklin University of Medicine and Science and a member of the FDA's Vaccines and Related Biological Products Advisory Committee.

Europe's approach

Some countries may go with vaccines based on the BA.1 Omicron subvariant this fall. It's not fully understood to what extent the sublineages of Omicron influence vaccine effectiveness, but some scientists who advise the World Health Organization argued that BA.1-based shots would be "more distinct" than other subvariants.

Moderna said it's developing a booster for the European Union, the UK and Australia that uses the original strain and BA.1.

The subvariant is largely extinct, but the company said its studies have shown that this booster candidate still drew "significantly higher neutralizing antibody responses" against BA.4 and BA.5 compared with the currently authorized booster.

Pfizer has said it too will make a vaccine that fits Europe's needs, as well as the needs in the US.

"Our program continues to focus on all variants of concern and we remain committed to the public health needs as defined by regulators, Europe and elsewhere," a spokesperson for Pfizer told CNN in an email.

Pfizer submitted its bivalent BA.1-specific vaccine to the European Medicines Agency in mid-July and told CNN it will be ready to distribute this fall, pending authorization.

In the United States, a vaccine updated for BA.4/5 got the go-ahead for fall.

Dr. Larry Corey, a vaccine development expert and professor of medicine and infectious disease division at Fred Hutchinson Cancer Research Center in Seattle, said the data makes a strong case for the addition. Research on infections shows that the BA.4 and BA.5 subvariants seem to induce stronger immune response than BA.1 and BA.2.

"We don't have the data yet. Certainly, we will know by the end of August," Corey said.

As with so much during the pandemic, scientists are making educated guesses and figuring things out as they go.

"We'll start sleeping better in a month, see whether it does well in animals, and we'll feel we made the right decision when we boost a bunch of people with the BA.4/BA.5 variants," Corey said.

A virus that breaks all the rules

Even as the virus changes, there is only so much vaccine makers can do, says University of Michigan epidemiologist Arnold Monto, who has served as acting chair of the FDA's vaccine advisory panel.

"Basically, we can only use those viruses that we know about," Monto said.

Omicron was a big change from previous variants, he said, and most evolutionary virologists don't think there will be such a big leap again. Rather, the changes will probably be along the Omicron lines.

But then again, "this has been a tricky virus. It has broken all the rules."

Regardless, Monto is confident that adding the BA.4/BA.5 element to the new vaccines will help.

"While we know that the latest viruses that we are encountering that will go into the vaccine probably are not going to the be the viruses in the coming fall and winter, the answer is not to chase them but to try and catch up and broaden them," he said.

In other words, vaccine makers will want to have a wide a distribution of immunity in the population. That's why they'll continue to include the original strain as well as Omicron.

It seems possible that we'll be facing different variants in the fall, but Dr. Eric Rubin, an adjunct professor of immunology and infectious disease at Harvard T.H. Chan School of Public Health, said there is a "very reasonable argument" that having some diversity in the immune response is still a good thing.

"For me, the most important thing we can measure right now is the breadth of immunity and not try to guess which strain is going to be there. That's probably more important than trying to guess what comes up in the fall," said Rubin, who is also on the FDA's vaccine advisory committee but was not a part of the Omicron booster discussion.

Evolution is trying to find its own path, however, and the virus will do whatever works for it as opposed to us. Down the line, he hopes we'll have even better vaccines that will prevent not just severe disease but infections as well.

"I don't think a perpetual game of catchup is going to work forever. We need to think about new approaches," Rubin said.

But he emphasized that more people should get vaccinated and boosted in order to keep cases, hospitalizations and deaths down.

Some people should still get boosted now

The FDA is still encouraging adults 50 and older and those with compromised immune systems to get a second booster now, with the current formula.

That would leave enough of an interval for them to get an updated booster in the fall.

The Biden administration has ended its conversations with the FDA about allowing adults under 50 to get a second booster with the current formula this summer.

Once boosters are updated for the fall, the FDA said, people who get boosted now "may consider getting one." Scientists say it will be important to get this updated version.

"The current vaccines do a pretty great job at keeping people out of hospitals," Rubin said. "I don't really want to dismiss what we've got there. Of course, we always want better."