Older COVID antibodies no longer effective against Omicron

If you were vaccinated or recovered from COVID-19 before 2022, you may not be as safe from reinfection as you think, according to a new antibody test that offers a clear window into the body’s immunity.

Researchers from the University of Toronto discovered that COVID-19 antibodies generated prior to 2022 are no longer effective against Omicron and later variants.

“We found out that people who were vaccinated at the end of last year or who got the booster shot by the end of last year, they have basically almost zero neutralizing antibodies against (Omicron),” said Dr. Igor Stagljar, who co-led the study and is a professor of biochemistry and molecular genetics at U of T’s Donnelly Centre and the Temerty Faculty of Medicine.

“This means actually that anybody who got COVID by the beginning of this year, or who got the booster by the beginning of this year, can get reinfected now,” he said.

His team’s study, recently published in Nature, detailed their creation of a new rapid test able to measure how effective neutralizing antibodies are at curbing the virus behind COVID-19 and its variants.

Unlike current antibody tests, which only count how many antibodies are present in the body, Stagljar’s test called neu-SATiN measures how effective those antibodies are at stopping COVID-19. It doesn’t matter how many antibodies we have if they aren’t effective, Stagljar said.

Antibodies are proteins able to recognize and bind to foreign invaders in the body. They’re tailor-made to attack specific targets, usually following infection or vaccination, and are crucial to the body’s immune response.

Neutralizing antibodies, in particular, bind to the COVID virus’s spike protein, blocking its entry into our cells. Most vaccines aim to spark neutralizing antibody creation for this reason.

Unfortunately, the viral spike protein has changed shape over later variants, Stagljar said. Incarnations like Omicron have become near-unrecognizable to antibodies built to target earlier variants.

After testing roughly 100 patients vaccinated against or recovered from COVID-19 before 2022, as well as FDA emergency-use-approved antibodies including casirivimab, imdevimab and etesevimab, Stagljar discovered none of the proteins were able to inhibit Omicron.

“That’s very scary,” he said.

Going forward, Stagljar said his team’s rapid antibody test will be a key tool in determining immunity against Omicron and its subvariants.

Unlike other neutralizing antibody tests which can take hours to complete and require specialized equipment, Stagljar’s test can be done in basic labs in just half an hour — a “major breakthrough,” he said.

It’s also far cheaper than the alternatives, costing roughly $3 a pop, Stagljar added.

U of T is currently negotiating a deal for their test to be licensed out to companies capable of scaling it up for Canadians to use, Stagljar said. In the meantime, they’ve partnered with Canadian vaccine maker Medicago to help test vaccine efficacy against future variants.

“I would really, really like to see this test being used more by Canadian agencies, because it’s fast, it’s accurate and it’s cheap,” Stagljar said. “…It costs less than a Starbucks coffee.”

Their paper only included samples taken before November of 2021, but Stagljar said they’ve since tested patients with antibodies generated just months ago.

“We have unpublished data saying that blood samples taken from February this year have almost zero neutralization capacity against (Omicron subvariants) BA.4 and BA.5,” he said.

BA.5 is quickly becoming the dominant COVID-19 strain in Ontario, and is notorious for its ability to dodge the body’s immune system.

Stagljar found vaccines “still confer significant protection from severe disease and death,” especially when taken within two to three months, he said.

However, people who were vaccinated four to five months ago “won’t have enough neutralizing antibodies to fight BA.4 or BA.5,” he continued.

“I would highly recommend people who are in risk groups to get their booster shots now” before a potential summer wave, Stagljar said.

His team’s findings corroborate with recent research in Nature and the New England Journal of Medicine that suggest Omicron — specifically BA.5 — can evade the immune response from earlier vaccination or COVID infection.

Additionally, new research published in Science found previous infections by Omicron offered little protection against reinfection by the variant.

On the other hand, previous studies in Nature and the American Society of Microbiology found killer T cells — another critical immune component that vaccines help create — are able to recognize Omicron despite being trained on earlier variants. This could explain why vaccines are still effective at preventing COVID-19 hospitalization or death, some researchers believe.

“You can’t ignore neutralizing antibodies, they are extremely important in protecting us against the infection in the first place,” said Dr. Isaac Bogoch, an infectious disease specialist at Toronto General Hospital.

“But we also have to remember there’s lots of different arms to the immune system apart from neutralizing antibodies, namely, your T cells,” he continued.

Bogoch noted that while Omicron subvariants like BA.5 are immune evasive, it doesn’t mean they’re totally invisible to the immune system. Vaccines still play an instrumental role in arming our bodies against COVID, he said.

That said, Bogoch believes taking routine booster shots every few months is “unsustainable.” There is plenty of evidence suggesting three shots are already “pretty incredible” at protecting against Omicron, despite the risk of reinfection, he said.

“All arrows point in the direction that the vaccines still protect against severe infection, hospitalization and death,” he added.

Dr. Prabhat Jha, a co-author on the paper, an epidemiologist at St. Michael’s Hospital and a professor of Global Health at the University of Toronto, agrees.

“If you had to choose between a vaccine and (natural immunity from infection), you’re way better off choosing a vaccine or third dose in particular,” he said, elaborating that vaccines provide much better, targeted protection against harsh outcomes than natural immunity would.

Despite the existence of killer T cells and other immune components, Jha said their antibody test still provides a “realistic” look at the body’s immunity against Omicron.

“Where neutralizing antibodies are detected, they’re more likely to correlate with the other types of immunity, including T cells or immune B cells,” he said. “So in that sense, it’s a better window into actual immunity.”

For now, the “single best thing” Canadians can do to protect themselves against Omicron and its subvariants is to get a booster dose.

“10 million Canadian adults or above age five do not have a third dose,” Jha said. “They should get it. It’s really that simple.”


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