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BA.5, now dominant U.S. variant, may pose the biggest threat to immune protection yet

The FDA recommended that Covid vaccine makers target two omicron subvariants — BA.4 and BA.5 — in new booster shots expected to come this fall.

A new version of omicron is dominant in the U.S.

The coronavirus subvariant known as BA.5 accounted for nearly 54% of the country's Covid cases as of Saturday, according to the Centers for Disease Control and Prevention. A similar subvariant, BA.4, makes up 17% more.

"They're taking over, so clearly they're more contagious than earlier variants of omicron," said David Montefiori, a professor at the Human Vaccine Institute at Duke University Medical Center.

The two subvariants also appear to evade protection from vaccines and previous infections more easily than most of their predecessors.

Montefiori estimated that BA.4 and BA.5 are about three times less sensitive to neutralizing antibodies from existing Covid vaccines than the original version of the omicron variant, BA.1. Other research suggests that BA.4 and BA.5 are four times more resistant to antibodies from vaccines than BA.2, which replaced the omicron variant as the U.S.'s dominant version of the coronavirus in April.

Francois Balloux, the director of the University College London Genetics Institute, said that's most likely another reason the subvariants have taken over.

"At this stage now, I think all these variants actually are roughly equally transmissible, so there’s not a huge difference," he said."It’s just some are slightly better at infecting people who have been vaccinated or infected by previous variants."

The Food and Drug Administration last week recommended modifying coming booster shots from Pfizer and Moderna to target BA.4 and BA.5 directly.

Pfizer has told NBC News that it could have an updated vaccine targeting BA.4 and BA.5 ready to be distributed in October.

The most common symptoms of BA.4 and BA.5

In the U.K., where BA.4 and BA.5 also account for the majority of new Covid cases, the most common Covid symptoms last week were runny nose, sore throat, headache, persistent cough and fatigue. Less than one-third of people surveyed reported fevers, according to data from the Zoe COVID Symptom Study, which asks people to self-report their symptoms through smartphone apps.

That’s consistent with the symptoms reported in the U.K. in the spring, when the BA.2 subvariant was dominant.

Balloux said no difference has been observed so far between BA.4 or BA.5 symptoms and those of previous subvariants. But people who were infected with the original version of the omicron variant during the winter may be susceptible to the newer subvariants.

"BA.1 and BA.2 are pretty different," he said, so the cross-protection "is not as great."

Balloux added, though, that "BA.2, BA.4 and B.5 from a neutralizing antibody perspective are essentially interchangeable." That might mean that people who got BA.2 infections have some protection now.

Montefiori said BA.4 and BA.5 also haven’t been found to cause more severe disease.

"There’s really no clear evidence that they’re more or less likely to make people sick and cause severe illness and death," he said.

Rather, rises in cases and hospitalizations observed in some places more likely have to do with fading vaccine protection.

"We have waning immunity now in the people who got boosted half a year or more ago," Montefiori said.

Will we need more booster shots, and when?

The FDA estimates that omicron-specific boosters from Pfizer and Moderna will become available in early to mid-fall.

"The companies are now scurrying to make the BA.4/BA.5-containing vaccine and test that clinically," Montefiori said.

But experts stressed that there may not be a dramatic difference in protection between additional boosts of the current vaccines and omicron-specific shots. Current vaccines still work well to prevent severe illness and death.

"The virus is moving in a direction of escaping our vaccines more and more, but it has not found a way to escape the vaccines to a really significant degree," Montefiori said.

For that reason, he added, people eligible for second boosters — those over 50 or the immunocompromised — may not want to wait.

"If your last boost was over six months ago, you might want to consider getting boosted again now with the current vaccine to keep your protection strong while we’re still getting through this pandemic," Montefiori said.

In addition, Balloux said, it’s hard to predict whether BA.5 will still be dominant later this year.

"Given the uncertainty, there’s no right or wrong," he said. "There are only trade-offs."

Europe and South Africa offer a preview of what comes next

Reported Covid case numbers have stayed relatively flat in the U.S. since May, but case numbers are on the rise globally.

By the end of June, new weekly cases were up by 32% in Southeast Asia, 33% in Europe and 47% in the region comprising the Middle East, Central Asia, North Africa and the Horn of Africa, the World Health Organization said. As of June 19, BA.5 accounted for 43% of omicron cases worldwide, while BA.4 accounted for 12%.

South Africa had a surge in cases driven by BA.4 and BA.5 this spring, and Covid hospitalizations are rising in the U.K. Experts said the trends likely indicate that the virus is getting better at reinfecting people and evading vaccine protection.

Still, the future of the pandemic will depend not just on the properties of variants, but also on human behavior and how much immunity has built up in the population.

"People tend to overestimate actually how much the virus has changed very recently," Balloux said. "There was a massive, massive change between delta and omicron, and then there was, again, a fairly massive change between BA.1 and BA.2."

That's not quite the case with BA.4 and BA.5, he said, although he noted another major shift in the virus's evolution could still come.

"I'm not saying it won't happen," he said.

CORRECTION (July 7, 2022, 7 a.m. ET): A previous version of this article misstated which group recommended boosters targeting BA.4 and BA.5. It was the FDA, not an FDA advisory committee.