Experimental Covid vaccine provides mutation-resistant T cell protection in mice

A second line of defense — the immune system’s T cells — may offer protection against COVID-19 even when vaccine-induced antibodies no longer can, new research from the University’s School of Veterinary Medicine finds. of Wisconsin.

Researchers have found that a new protein-based vaccine against the original version of the COVID-19 virus was able to teach mouse T cells how to recognize and kill cells infected with new mutated versions of the virus. This T-cell protection worked even when the antibodies lost their ability to recognize and neutralize the mutated SARS-CoV-2, the virus that causes COVID-19.

Marulasiddappa Suresh

“Antibodies prevent COVID-19 infection, but if new variants evade these antibodies, T cells are there to provide a second line of protection,” says lead scientist Marulasiddappa Suresh, professor of immunology and associate dean in research at the School of Veterinary Medicine. .

The study, published in the Proceedings of the National Academy of Sciences on May 13, investigates the role of T cells, a specialized type of white blood cell, in defense against COVID-19 when antibodies fail.

When you receive a COVID-19 vaccine, your body learns to produce antibodies, immune system proteins that bind to and neutralize SARS-CoV-2. These antibodies circulate in the blood and protect you from disease by patrolling the nostrils, airways and lungs and eliminating the virus before it causes infection or illness.

However, as SARS-CoV-2 mutates, these highly specific antibodies are less able to recognize new viral variants – particularly if the changes occur on the virus’ spike protein, where vaccine antibodies bind. This was particularly evident during the recent surge of the omicron variant of SARS-CoV-2, which has a staggering 37 mutations on its spike protein, making it better able to evade antibodies targeting the virus’ spike protein. ‘origin.

“The biggest problem right now is that none of our current COVID-19 vaccines offer complete protection against infection by the emerging variants, especially the omicron BA.1 and BA.2 sublines. “, says Suresh.

This is where T cells can help. Killer T cells help the immune system by hunting down and eliminating “virus factories” – infected cells, Suresh says. So when antibodies cannot neutralize the virus before infection, T cells can clear it quickly, causing mild or no symptoms.

With this information in hand, the UW-Madison research team, co-led by Suresh and professor of pathobiological sciences Jorge Osorio and assisted by scientist Brock Kingstad-Bakke and doctoral student Woojong Lee, explored how T cells and antibodies may work to prevent COVID -19 infections altogether.

Brock Kingstad-Bakke wearing a surgical grade mask and white lab coat and purple rubber gloves, watching a lab experiment

Brock Kingstad-Bakke, scientist at the UW School of Veterinary Medicine. Photo courtesy of the School of Veterinary Medicine

Researchers have developed an experimental protein-based vaccine containing the unmutated version of the spike protein from the original SARS-CoV-2 virus. This vaccine was also designed to elicit a strong T cell response to the viral spike protein, allowing the lab to test how well T cells can protect against COVID-19 infection in the presence and absence of virus neutralizing antibody.

After injecting mouse models with their vaccine, the researchers then exposed them to two variants of SARS-CoV-2 and tested their susceptibility to infection under different conditions.

While the vaccine-stimulated antibodies were unable to neutralize the mutated variants of SARS-CoV-2, the mice were still immune to COVID-19 caused by the mutated viruses, due to the action of the cells T induced by the vaccine.

Unlike antibodies, T cells are able to detect unknown viral strains because the viral fragment they recognize does not change significantly from variant to variant.

This work has important implications for future T-cell vaccines that could provide broad protection against emerging SARS-CoV-2 variants. The experimental vaccine is protein-based and designed to evoke a strong T-cell response, differentiating it from currently available mRNA vaccines.

Now the Suresh lab is studying how exactly T cells defend against SARS-CoV-2 and whether commercially available COVID-19 vaccines can induce these same T cell immunity mechanisms to protect against emerging variants when the virus avoids established antibodies.

“I see the next generation of vaccines will be able to provide immunity against current and future variants of COVID-19 by stimulating both broadly neutralizing antibodies and T-cell immunity,” Suresh says.

This work was supported in part by the National Institutes of Health (Grants U01 AI124299, R21 AI149793-01A1).

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