A new SARS-CoV-2 variant, Pirola (BA.2.86), is spreading globally and is causing concern due to its high mutation rate. Researchers at the La Jolla Institute for Immunology are using a database of immune epitopes to predict T cell responses to Pirola, and they found that existing vaccines and previously exposed variants, such as Omicron, still provide significant protection. Although these results are promising, they are still predictive and require further experimental validation.
La Jolla Institute for Immunology scientists used bioinformatics to predict how T cells would adapt to fight highly mutated Pirola variants. In August, researchers detected a new SARS-CoV-2 "variant of concern" in patients in Israel and Denmark. Since then, the variant, known as BA.2.86 or "Pirola," has spread around the world. The Pirola variant is alarming because it is highly mutated. In fact, Pirola is no less mutated than the Omicron variant compared to the SARS-CoV-2 variant it was originally vaccinated against.
As Pirola spreads, researchers at the La Jolla Institute for Immunology (LJI) are investigating whether COVID-19 vaccines (or SARS-CoV-2 vaccines from previous exposure) can still protect people from severe disease.
Alessandro Sette, a professor at LJI and Ph.D. in biological sciences, said: "People are worried that viruses with so many mutations will 'escape' T cell immunity."
Now, a new study in the journal Cell Host & Microbe shows that T cells can see through Pirola's mutations and lock onto their targets. "There is positive news from our analysis," said Dr. Alba Grifoni, assistant research professor. "It appears that people who have been previously exposed to Omicron or vaccinated with the new bivalent vaccine may be armed with T cells that can 'catch up' and mount a specific response against Pirola."
For the new study, Sette and Grifoni took advantage of a resource called the Immune Epitope Database (IEDB). The database contains valuable research collected by immunologists around the world, describing how immune cells recognize fragments, or "epitopes," on microorganisms.
Using a wealth of data in the IEDB, researchers have gained a detailed understanding of how T cells are "trained" to target SARS-CoV-2 epitopes by COVID-19 vaccines or by previous exposure to SARS-CoV-2. The researchers extracted this IEDB data and developed a bioinformatics pipeline to predict how these T cells would respond to Pirola variants.
"We modeled T cell responses 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% of the fragments recognized by the CD4+ "helper" T cell response and 89% of the CD8+ "killer" T cell epitopes did not change, or "remained the same" between the variants.
The researchers found fewer conserved T-cell epitopes on Pirola's "Spike" protein, which was expected since it carries most of the variation. Only 56% of CD4+ "helper" T cell epitopes and CD8+ "killer" T cell epitopes are conserved on this major structural protein. This is a potential problem because current COVID-19 vaccines are designed to only allow immune cells to recognize and latch on to Spike epitopes.
However, when the researchers looked closely at the Spike fragment, they found that 96% of the CD4+ "helper" T cell epitopes and 62% of the CD8+ "killer" T cell epitopes were so similar that it was still possible for the T cells to recognize them.
In short, if Pirola wants to evade T cells, it doesn't do a good job.
"Many epitopes recognized by the immune system remain unchanged on the new Pirola variant. It is predicted that this virus will still be recognized by T cells," Sette said.
"It's also possible that T cells 'go after' Pirola's newly mutated peptides, launching new responses against these epitopes, as we've seen with other variants," Grifoni added. "We think this may be one reason why we don't see more severe disease in cases of Pirola virus infection or other recent variants, despite the evolution of the virus."
Grifoni emphasized that these findings are predictions and not based on observations of actual Pirola infections. Still, she thinks it's important to see how observations and predictions are reflected in recent actual research. We still need experimental validation, but we have established several collaborative institutions around the world that are working on this issue.
Sette added that many people are still susceptible to SARS-COV-2, even with the Pirola variant. This is why people should still get vaccinated, especially the latest ones.
The researchers are currently collecting experimental data to further understand T cell responses to variants and further enhance their predictive tools to understand how people who have received bivalent vaccines and/or "breakthrough" infections will develop T cell responses to future variants.
Reference "Predicting that existing SARS-2-specific T cells will cross-recognize BA.2.86" published by Alessandro Sette, John Sidney and Alba Grifoni in the journal Cell Host & Microbe on December 8, 2023.
DOI:10.1016/j.chom.2023.11.010
Compiled source: ScitechDaily