T-cells Can Fight BA.2.86 COVID Variant

The body's initial line of defense, T cells, are well suited to combat the recently identified highly mutated BA.2.86 or "Pirola" sub-variant of COVID-19, reveals a study published in the journal Cell Host & Microbe (1^✔ ✔Trusted Source
Pre-existing SARS-2-specific T cells are predicted to cross-recognize BA.2.86

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Body’s Immune Cells to Combat New ‘Pirola’ COVID Variant

In August, researchers detected a new SARS-CoV-2 "variant of concern" in patients in Israel and Denmark. Since then, this variant, dubbed BA.2.86 has made its way around the globe. The Pirola variant has raised alarms because it is as mutated as the Omicron variant was, compared with the early SARS-CoV-2 variant included in the original vaccinations. "There's a concern that a virus with such a high number of mutations would 'escape' T cell immunity," said Alessandro Sette, Professor at La Jolla Institute for Immunology (LJI) in the US.

The new study suggests that T cells can see right through Pirola's mutations and find their targets. "Our analysis suggests there is positive news," said LJI Research Assistant Professor Alba Grifoni.

For the new study, the team turned to a resource called the Immune Epitope Database (IEDB). This database houses valuable findings -- collected by immunologists around the world -- describing how immune cells recognize fragments, or "epitopes," on microbes. The data helped researchers with a detailed picture of how COVID-19 vaccines or previous SARS-CoV-2 exposure "trains" T cells to target SARS-COV-2 epitopes.

They extracted these 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," Grifoni said. The researchers found that most T cells could still target epitopes on Pirola.

Overall, 72 percent of the fragments recognized by CD4+ "helper" T cell responses and 89 percent of CD8+ "killer" T cell epitopes were unchanged, or "conserved," between the variants. The researchers found fewer conserved T cell epitopes on Pirola's "Spike" protein, as expected given it harbors most of the mutations.

Further, only 56 percent of CD4+ "helper" T cell epitopes and CD8+ "killer" T cell epitopes were conserved on this major structural protein. That was a potential problem because current COVID-19 vaccines are designed to only teach immune cells to recognize and target Spike epitopes.

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Yet when the researchers took a closer look at the Spike fragments, they found that 96 percent of CD4+ "helper" T cell epitopes and 62 percent of CD8+ "killer" T cell epitopes were similar enough that T cells could probably still recognize them. In short, if Pirola wants to evade T cells, it isn't doing a very good job.

"A lot of the epitopes recognized by the immune system are still conserved on the new Pirola variant," said Sette. "We strongly predict that the virus will still be recognized by T cells." "T cells may also be able to 'run' after the Pirola's newly mutated peptides to mount a new response against those epitopes, as we saw for other variants," added Grifoni.

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"We think that may play a role in why, despite viral evolution, we haven't seen more severe disease in cases of Pirola infection or other more recent variants." Grifoni emphasized that these findings are predictions, not observations based on actual Pirola infections. Still, she thinks it is important to see how these "in silico" (in a computer) predictions reflect in recent real-world studies.

Reference:

1. Pre-existing SARS-2-specific T cells are predicted to cross-recognize BA.2.86 - (https://www.sciencedirect.com/science/article/abs/pii/S1931312823004602)

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