Study shows T cells can fight new SARS-CoV-2 variant ‘Pirola’

In August, researchers detected a new “variant of concern” of SARS-CoV-2 in patients in Israel and Denmark. Since then, this variant, called BA.2.86 or “Pirola”, has toured the world. The Pirola variant has raised the alarm because it is highly mutated. In fact, Pirola is as mutated as the omicron variant, compared to the first SARS-CoV-2 variant included in the original vaccinations.

As Pirola spreads, La Jolla Immunology Institute (LJI) researchers are studying whether COVID-19 vaccines (or previous exposure to SARS-CoV-2) can still protect people from illness severe.

“There is concern that a virus with such a high number of mutations will ‘escape’ T cell immunity,” says Professor Alessandro Sette, Dr. Biol.Sci, from LJI.

Now, a new study in Cellular host and microbe suggests that T cells can see through Pirola mutations and find their targets. “Our analysis suggests there is some positive news,” says Alba Grifoni, Ph.D., research assistant professor at LJI. “It appears that prior exposure to the omicron – or vaccination with the newer bivalent vaccines – can arm a person with T cells capable of ‘catching up’ and generating specific responses to combat Pirola.”

Exploiting bioinformatics

For the new study, Sette and Grifoni turned to a resource called the Immune Epitope Database (IEDB). This database contains valuable findings, collected by immunologists around the world, describing how immune cells recognize fragments, or “epitopes,” on microbes.

Thanks to the wealth of IEDB data, researchers already had a detailed picture of how COVID-19 vaccines or previous exposure to SARS-CoV-2 “trained” T cells to target SARS-COV-2 epitopes. The researchers extracted this IEDB data and developed a bioinformatics pipeline to predict how these T cells would respond to the Pirola variant.

“We simulated the T cell response to Pirola based on experimental and predicted data from previous SARS-CoV-2 variants,” says Grifoni.

The researchers found that most T cells could still target Pirola epitopes:

• Overall, 72 percent of fragments recognized by CD4⁺ “Helper” T cell and 89 percent CD8 cell responses⁺ “Killer” T cell epitopes were unchanged, or “conserved,” between variants.
• The researchers found fewer conserved T cell epitopes on Pirola’s “Spike” protein, as expected given that it harbors most of the mutations. Only 56 percent of CD4⁺ Epitopes of “helper” T cells and CD8⁺ The “killer” T cell epitopes were conserved on this major structural protein. This was a potential problem because current COVID-19 vaccines are designed only to teach immune cells to recognize and target Spike epitopes.
• Yet when the researchers looked more closely at the Spike fragments, they found that 96 percent of CD4⁺ Epitopes of “helper” T lymphocytes and 62% of CD8⁺ The epitopes on the “killer” T cells were similar enough that the T cells could probably still recognize them.

Anyway, if Pirola wants to escape the T cells, he’s not doing a very good job.

“A large number of epitopes recognized by the immune system are still preserved on the new Pirola variant,” explains Sette. “We strongly predict that the virus will still be recognized by T cells.”

“T cells might also be able to ‘run’ after newly mutated Pirola peptides to mount a new response against these epitopes, as we have seen for other variants,” adds Grifoni. “We think this may explain why, despite viral evolution, we have not seen more severe disease in cases of Pirola infection or other newer variants.”

Next steps

Grifoni emphasizes that these results are predictions and not observations based on actual Pirola infections. Still, she thinks it’s important to see how these “in silico” (in a computer) predictions reflect in recent real-world studies. “We still need experimental validation, but we have established several collaborations around the world that are studying this question as we speak,” says Grifoni.

Many people are still vulnerable to infection by SARS-COV-2, even by the Pirola variant, adds Sette. “This is why people should continue to be vaccinated, especially with updated vaccines.”

Researchers are currently collecting experimental data to learn more about T cell responses to variants and further strengthen their prediction tools. Grifoni is particularly curious to understand exactly how people who have received bivalent vaccine boosters and/or “breakthrough” infections develop T-cell responses against future variants.