The subvariants recently caused a fresh wave of infections in South Africa, and are pushing the U.K. to the brink of another wave of the disease.

BA.5 recently became the dominant subvariant in the U.S., accounting for almost a quarter of COVID infections last week, while BA.4 made up just over 11% of new cases, CDC data showed.

In a letter to the editor of the New England Journal of Medicine on Wednesday, experts from Harvard Medical School’s Beth Israel Deaconess Medical Center (BIDMC) outlined their findings from a recent analysis of 54 individuals’ antibody protection against various Omicron subvariants.

Of the participants in their study, 27 had been vaccinated and boosted with the Pfizer-BioNTech vaccine, and 27 had been infected with either the BA.1 or BA.2 Omicron subvariant a median 29 days earlier.

All but one of the participants who had recently been infected with the virus had also been vaccinated.

The researchers tested participants’ immune responses to the BA.1, BA.2, BA.4, and BA.5 subvariants, as well as a sample of the original strain of COVID-19 (WA1/2020).

Six months after the initial two immunization doses, median antibody levels against WA1/2020 were 21 times higher than they were against Omicron subvariants BA.4 and BA.5.

Two weeks after a booster shot, antibody levels increased substantially, but remained three times higher against the BA.1 and BA.2 subvariants than they were against BA.4 and BA.5.

Spokespeople for Pfizer and BioNTech were not immediately available to discuss the implications of the study’s findings.

The BIDMC study found that immunity gained through infection with the BA.1 or BA.2 Omicron subvariants was also far less effective against BA.4 and BA.5 than it was against earlier subvariants.

Again, scientists observed a threefold reduction in antibody levels against BA.4 and BA.5 compared to the BA.1 subvariant.

Subvariants ‘substantially escape antibodies’

Researchers said their data showed that the BA.4 and BA.5 subvariants “substantially escape neutralizing antibodies induced by both vaccination and infection.”

Adding that the findings suggested “the Omicron variant has continued to evolve with increasing neutralization escape,” the research team said the study provided “immunologic context for the current surges caused by the BA.4 and BA.5 subvariants in populations with high frequencies of vaccination and BA.1 or BA.2 infection.”

Their findings come after a Chinese study published in the Lancet Infectious Diseases journal on Monday drew similar conclusions about BA.4 and BA.5’s ability to evade immunity.

Scientists studied antibody levels in just over 100 people to examine how their immune responses varied when confronted with the BA.1, BA.2, BA.2.11, BA.2.12.1, BA.2.13, BA.4, and BA.5 Omicron subvariants.

They found that in people who had received two doses of the Sinopharm COVID vaccine, antibody levels drastically subsided when it came to fighting off Omicron subvariants as compared to neutralizing earlier strains of the virus.

“We found that two [Sinopharm] doses induced detectable neutralizing antibodies against spike protein mutation D614G in 21 (84% of) individuals, but neutralizing activity against omicron subvariants was not or only minimally detectable,” researchers on the Chinese study said.  

The D614G mutation was present in the original strain of COVID-19 first identified in the Chinese city of Wuhan.

Only between 24% and 53% of people who had been boosted with either the Sinopharm or the Anhui Zhifei Longcom vaccine had any immune response to any Omicron subvariant, the Lancet study said.

Among 18 participants who had had a BA.1 breakthrough infection, researchers observed a similar level of antibodies against the original strain of the virus that was produced in response to all Omicron subvariants—except BA.4 and BA.5, which generated an immune response with three times fewer antibodies.

Meanwhile, breakthrough infections caused by BA.2.2 led to lower immune responses to all Omicron subvariants, apart from the BA.2 mutation.

The U.S. recorded 185,237 new cases of COVID-19 on Tuesday, according to data from the CDC.