(CNN) — This fall, Americans could get an mRNA COVID-19 booster shot unlike any before.
Both Pfizer and Moderna are working on bivalent boosters: vaccines made up of the old formula and a new one that targets the BA.4 and BA.5 omicron subvariants.
If the vaccines meet US Food and Drug Administration (FDA) standards, they will likely be available as early as September, according to the FDA.
But cases are high now. About 124,000 new cases are reported each day, a far cry from the levels seen during the omicron surge, but close to the peak rates of the delta variant surge, and the case count is at its lowest.
Some experts question whether omicron-specific boosters will arrive in time to make a difference, and whether they will actually offer more protection than current vaccines.
a prediction game
Current vaccines are based on the original strain of the virus and offer almost total protection, even against infection, from the start. With the new variants in circulation, vaccines are still 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, believes that vaccines with an omicron-targeting component will be useful, but with limitations.
“I just wish the time had been sooner so we could deal with the type of BA.5 outbreak that we have now,” he said.
With the highly contagious BA.5 subvariant now dominant, the goal of minimizing the number of infections is “a bit lost,” but the new vaccines should help keep hospitalizations and deaths low, Chang said.
“I think that whenever you can introduce additional strains or variants into a vaccine, the human body’s immune response tends to be a little more broad-based and resistant, and potentially more durable,” he said.
But it’s impossible to know right now which variant will be dominant in a couple of months, how different it will be from 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 so more likely they will increase. As in the case of the flu, scientists believe that the coronavirus is transmitted more effectively in cold weather. It also spreads more easily when people pass more time indoors.
Dr. Edward Michelson, director of the Department of Emergency Medicine at Texas Tech University Health Sciences Center in El Paso, is seeing many patients again, including those who had omicron earlier in the year.
“Omicron isn’t protecting people even a few months after they’ve gotten sick from it. These subvariants are getting them back, to my surprise,” Michelson said. “The good news is that most patients do not need hospitalization.”
Still, 375 people die on average every day in the US from covid-related causes, according to the CDC.
“A new vaccine could be really profitable”
The Covid-19 Scenario Modeling Center, a group of scientists from across the country that creates projections for the coming year, predicts a rise in hospitalizations through early fall. But the modeling suggests that a booster campaign will put a dent in these numbers, according to Justin Lessler, an epidemiologist at the University of North Carolina who works with the group.
Although scientists are still trying to determine exactly how effective new vaccines are in protecting people, Lessler said the model assumes the reformulated vaccine would be about 80% effective against infection with currently circulating strains. But that depends on how many people actually get an updated booster.
“In the absence of real new variants, that kind of efficacy would be enough to reduce the current circulation if we have broad acceptance of vaccines,” Lessler said. “A new vaccine could be really profitable, especially if we can get it to a wide swath of the population.”
Ideally, public health campaigns would encourage people to get vaccinated against the flu and Covid-19 at the same time, he said.
Lessler presented an earlier version of the model to the FDA’s independent immunization advisors, who voted in June to recommend that vaccine makers include the BA.4 and BA.5 subvariants in the fall booster. The advisers said that including an element of the omicron variant would offer more protection.
“While it’s impossible for anyone to predict which variants will be circulating at that point, the goal, as I see it, is to add the sub-variants that are most likely to provide us with that broad spectrum of antibodies that will hopefully prevent serious disease, which that’s really what we’re trying to do,” said Dr. Archana Chatterjee, dean of the Rosalind Franklin University of Medicine and Science Chicago School of Medicine and a member of the FDA Advisory Committee on Vaccines and Related Biologics.
Some countries may opt for vaccines based on the BA.1 subvariant of omicron this fall. it is not known for sure the extent to which omicron subvariants influence vaccine efficacy, but some scientists advising the World Health Organization they maintain that vaccines based on the BA.1 subvariant would be “more distinct” than other subvariants.
Moderna said it is developing a booster for the European Union, the United Kingdom and Australia that uses the original strain and BA.1. This subvariant is largely extinct, but the company said its studies have shown this booster candidate still attracted “significantly higher neutralizing antibody responses” against subvariants. BA.4 and BA.5 compared to the currently authorized booster.
Pfizer it has said that it will also make a vaccine that fits the needs of Europe, as well as those of the United States.
“Our program continues to focus on all variants of interest and we remain committed to public health needs as defined by regulators, in Europe and beyond,” a Pfizer spokesperson told CNN in an email.
Pfizer submitted its BA.1-specific bivalent vaccine to the European Medicines Agency in mid-July and told CNN it will be ready for distribution this fall, pending authorization.
In the United States, an updated vaccine for BA.4/5 got the go-ahead for the fall.
Dr. Larry Corey, an expert in vaccine development and a professor of medicine and in the division of infectious diseases at the Fred Hutchinson Cancer Research Center in Seattle, said the data makes a strong case for their addition. Infection research shows that BA.4 and BA.5 subvariants appear to induce a stronger immune response than BA.1 and BA.2.
“We don’t have the data yet. Certainly we’ll know by the end of August,” Corey said.
As with many things during the pandemic, scientists are guessing and figuring things out as they go.
“We’ll start sleeping better within a month, see if it behaves well in animals, and feel like we’ve made the right decision when we boost a group of people with the BA.4/BA.5 variants,” Corey said.
A virus that breaks all the rules
Even if the virus changes, there’s not much that vaccine makers can do, says University of Michigan epidemiologist Arnold Monto, who has been acting chairman of the FDA’s advisory panel on vaccines.
“Basically, we can only use the 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 jump again. Rather, the changes will probably be along the lines of the omicron variant.
But again, “this has been a complicated virus. It has broken all the rules.”
In any case, Monto is confident that adding the BA.4/BA.5 element to new vaccines will help.
“Even though we know that the latest viruses that we’re finding that are going to go into the vaccine probably won’t be the viruses of next fall and winter, the answer is not to go after them, but to try to catch up and scale them up,” he said.
In other words, vaccine manufacturers will want to have a wide distribution of immunity in the population. That is why they will continue to include the original strain and the omicron.
It seems possible that we will be facing different variants in the fall, but Dr. Eric Rubin, associate professor of immunology and infectious diseases at the Harvard TH Chan School of Public Health, said there is a “very reasonable argument” that having some diversity on 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 what strain is going to be there. That’s probably more important than trying to guess what’s going to show up in the fall,” said Rubin, who also is on the FDA’s vaccine advisory committee, but was not involved in the debate over the omicron booster.
However, evolution is trying to find its own way, and the virus will do what suits it, unlike us. Later, he hopes we will have even better vaccines that prevent not only serious diseases, but also infections.
“I don’t think a perpetual catch-up game is going to work forever. We have to think of new approaches,” Rubin said.
But he insisted that more people need to be vaccinated and boosted to keep cases, hospitalizations and deaths low.
Some people should get vaccinated now
The FDA continues to urge adults age 50 and older and those with weakened immune systems to get a second booster now, using the current formula. This would leave enough time for them to receive an updated booster in the fall.
The Biden administration has ended talks with the FDA to allow adults under the age of 50 to receive a second booster dose of the current formulation this summer.
Once boosters are updated for the fall, the FDA said, people who get a booster now “may consider getting one.” Scientists say it will be important to get this updated version.
“Current vaccines do a great job of keeping people out of hospitals,” Rubin said. “I don’t want to discount what we have there. Of course, we always want something better.”