Wednesday, November 30, 2022

BA. 275.2: new Omicron subvariant can evade nearly all protective antibodies: study

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A new study from researchers in Sweden suggests the world could be in for a dramatic surge in COVID-19 cases this winter due to new mutations creating variants that could avoid immunity from vaccines or previous infections.

The variant BA.2.75.2, one of the latest developments in the Omicron lineage of COVID-19, can evade the majority of neutralizing antibodies in the blood, the study found, and is also resistant to several monoclonal antibody antiviral treatments that were created to treat those ill with COVID-19.

The mutations that make this possible in BA.2.75.2 are popping up in other variants as the virus continues to expand and evolve, researchers say — and it’s still unknown whether bivalent vaccines will provide more robust immunity against this particular variant.

The study, published in the Lancet Infectious Diseases on Thursday, looked at three subvariants of Omicron, and found that although vaccines do still provide some protection against them, certain variants are better than others at escaping antibodies.

“While antibody immunity is not completely gone, BA.2.75.2 exhibited far more dramatic resistance than variants we’ve previously studied, largely driven by two mutations in the receptor binding domain of the spike protein,” Ben Murrell, corresponding author and assistant professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet, said in a press release.

Currently BA.5 is one of the most dominant variants in North America, the study said. According to the most recent data from the Public Health Agency of Canada, BA.5 and BA.4 are currently dominating in Canada. As well, the World Health Organization has been monitoring other variants, including BA.2.75. 

BA.2.75.2 is the latest mutation of BA.2.75. Previous research has shown that BA.2.75 is not as efficient as BA.5 at escaping antibodies, but BA.2.75.2 has additional mutations that made researchers sit up and take notice.

Several specific mutations within the variant BA.2.75.2 had already been associated with a higher escape percentage in previous variants, the study said. But BA.2.75.2 combines mutations in a way that could make it potentially much more infectious.

A diagram accompanying the research pointed out structural differences in the receptor binding domain between BA.2 and BA.2.75, as well as differences between BA.2.75 and BA.2.75.2 in order to show how this variant continued to mutate.

And researchers say that BA.2.75.2 is far from COVID-19’s final form.

“We now know that this is just one of a constellation of emerging variants with similar mutations that will likely come to dominate in the near future,” Murrell said. “We should expect infections to increase this winter.”

To look at the variant in a real world setting, researchers used donated blood samples from around 75 donors which was collected at three intervals: in 2021 before Omicron had emerged and twice in 2022 after a surge in cases and the third vaccine dose rollout.

“Across all three timepoints, neutralisation of BA.2.75.2 by serum antibodies was significantly lower than all other variants tested,” the study stated.

They observed that two mutations that set BA.2.75.2 apart from BA.2.75 “contributed to the significantly enhanced resistance” of the newer variant.

Researchers also looked at whether a variety of preclinical monoclonal antibody treatments available in Sweden were able to neutralize the variants BA.2.75.2, BA.4.6 and BA.2.10.4.

These treatments are used primarily for those who are at a high-risk of developing severe illness if they contract COVID-19.

A treatment called cilgavimab was effective against BA.2.10.4, while another called sotrovimab showed weak results against BA.2.75.2 and BA.2.10.4, with better results against BA.4.6.

Only one treatment — bebtelovimab — was able to “potently” neutralize BA.2.75.2 and the other variants, researchers found.

Bebtelovimab, which was developed by a lab in Vancouver in connection with a U.S. company, has been approved for use in the U.S., but not in Canada yet.

The release noted that scientists still don’t know if this variant will increase hospitalizations in the winter, but the evidence suggests that if BA.2.75.2 begins circulating more, those regions could certainly see more cases due to this variant’s increased ability to conquer the protective shield of vaccines or prior infection.

Researchers hope that the new bivalent vaccines, which were modified to include protection against early Omicron variants, may provide more robust antibodies to block these newer variants, but scientists don’t have enough data yet.

“We expect them to be beneficial, but we don’t yet know by how much,” Murrell said.

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