T Cells: A Potential Secret Weapon Against the Latest COVID “Variant of Concern”

The global detection of a new SARS-CoV-2 variant, Pirola (BA.2.86), has caused concern due to its high rate of mutation. La Jolla Institute for Immunology's researchers are employing the Immune Epitope Database to predict T cell responses to the Pirola variant. Their findings suggest that current vaccines, as well as previous exposure to variants such as Omicron, may still provide significant protection. However, these results remain predictive and need further experimental validity. Credit for this information goes to SciTechDaily.com.

Biologists at LJI are using bioinformatics to predict possible T cell adaptations in response to the Pirola variant, which is highly mutated.

A new SARS-CoV-2 "variant of concern" was identified in Israel and Denmark back in August, and since then, this variant, known as BA.2.86 or "Pirola," has been spreading globally. This is worrying because of Pirola's high mutation rate, similar to the mutation rate of Omicron when compared to the early SARS-CoV-2 variant used in the initial vaccinations.

In response to the spread of Pirola, LJI researchers are investigating if COVID-19 vaccines, or previous exposure to SARS-CoV-2, could protect individuals from severe illness.

LJI Professor Alessandro Sette thinks high-rate mutations might make the virus escape T cell immunity. However, a new study in Cell Host & Microbe suggests that T cells can bypass the Pirola's mutations and identify their targets correctly. According to LJI Research Assistant Professor Alba Grifoni, Ph.D., this observation indicates positive news, as previous exposure to Omicron or vaccination with the new bivalent vaccines might equip an individual with T cells capable of generating responses specifically tailored for combating Pirola.

The researchers turned to the Immune Epitope Database (IEDB) for their latest study. This repository contains findings on how immune cells recognize fragments or "epitopes" on microbes collected by global immunologists.

The researchers already had a clear image of how COVID-19 vaccines or previous SARS-CoV-2 exposure trains T cells to target SARS-CoV-2 epitopes thanks to the IEDB. They utilized this data to design a bioinformatics pipeline predicting T cell responses to the Pirola variant.

Grifoni explained that they simulated the T cell response to Pirola using experimental and predicted data from former SARS-CoV-2 variants. Their findings suggest that most T cells could still target the Pirola epitopes.

In essence, Pirola is unsuccessful in evading T cell responses. Grifoni adds that numerous recognized epitopes by the immune system are still conserved in the new Pirola variant. Sette believes that T cells will still recognize the virus.

Grifoni explains that T cells might also produce a new response against the Pirola's newly mutated peptides, as they've seen with other variants. This could be a factor in why more severe disease hasn't been observed in recent variants, including Pirola, despite viral evolution.

Grifoni emphasizes that these findings are predictions and not based on actual Pirola infections. Nonetheless, she believes it's crucial to understand how these computer-based predictions apply to real-world studies. Despite the need for experimental validation, the investigation into this question is currently ongoing via global collaborations, according to Grifoni.

Even the Pirola variant can still infect several individuals, as Sette adds. Hence the need for vaccination, particularly with updated vaccines.

The researchers are in the process of collecting experimental data to better understand T cell responses to various variants and strengthen their prediction tools. Grifoni expresses particular interest in determining the response of individuals who had bivalent vaccine boosters or experienced "breakthrough" infections to future variants.