Studio portrait of Marulasiddappa Suresh

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

According to new research from the University of Wisconsin School of Veterinary Medicine, a second line of defense — the immune system’s T cells — can protect against COVID-19, even when vaccine-induced antibodies can no longer.

The researchers found that a new protein-based vaccine against the original version of the COVID-19 virus could 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 antibodies lost their ability to recognize and neutralize mutated SARS-CoV-2, the virus that causes COVID-19.

Marulasiddappa Suresh

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

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

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

However, because SARS-CoV-2 mutates, these highly specific antibodies are less able to recognize new viral variants, especially if the changes occur on the virus’s spike protein, where the vaccine’s antibodies bind. This was especially evident during the recent wave of the SARS-CoV-2 omicron variant, which is a staggering 37 mutations on its spike protein, making it better able to evade antibodies that target the spike protein of the original virus.

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

That’s where T cells can help. Killer T cells help the immune system by hunting for and eliminating “virus factories” — infected cells, Suresh says. So when antibodies can’t neutralize the virus prior to infection, T cells can quickly clear it, causing mild or no noticeable 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 PhD student Woojong Lee, explored how T cells and antibodies might work to fight COVID. prevent -19 infection altogether.

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

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

The researchers developed an experimental protein-based vaccine that contains the unmutated version of the spike protein from the original SARS-CoV-2 virus. This vaccine is also designed to elicit a strong T cell response to the viral spike protein, allowing the lab to test the extent to which T cells can protect against COVID-19 infection in the presence and absence of virus neutralizing antibodies.

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

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

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

This work has important implications for future T cell-based vaccines that could provide broad protection against emerging SARS-CoV-2 variants. The experimental vaccine is protein-based and designed to elicit a strong T-cell response, which sets it apart 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 the same mechanisms of T cell immunity to protect against emerging variants when the virus evades established antibodies.

“I see that the next generation of vaccines can provide immunity against current and future COVID-19 variants by boosting 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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