This study underscores the key role of T cells in providing long-term protection against evolving COVID variants
A new study by END-VOC researchers at ISGlobal and UCL reveals that while the highly mutated SARS-CoV-2 BA.2.86 variant, also known as Pirola, evades the action of many neutralizing antibodies, T cells—key players in the immune system—remain largely resilient. The findings underscore the importance of T-cell immunity in the fight against COVID-19, even as the virus evolves.
Why Pirola
The Omicron subvariant BA.2.86, also known as ‘Pirola’, raised significant concerns due to its 63 amino acid changes compared to the ancestral SARS-CoV-2 Wuhan spike (S) protein. “The magnitude of change between Pirola and its BA.2 ancestor is comparable to the genetic leap observed between the Delta and Omicron variants,” explains UCL researcher François Balloux. The worry was that immunity to previous variants, acquired through infection or vaccination, would not be protective enough against Pirola. This is where Carlota Dobaño and Gemma Moncunill’s team at ISGlobal came in. Together, the END VOC researchers tested immune responses in individuals who were vaccinated and who, in most cases, had also been infected with Omicron or pre-Omicron variants.
What they found
They found that BA.2.86 significantly evades neutralizing antibodies, making it harder for the immune system to block the infection. However, T-cell responses—responsible for recognizing and destroying infected cells showed only a modest decrease in their ability to recognize the new variant. “T-cell responses remained generally well preserved in individuals previously exposed through vaccination and/or infection,” says first author of the study, Rocio Rubio. On average, T-cell recognition of Pirola decreased by just 7.5% to 14.2%, depending on the specific immune markers analysed.
T cell resilience
Computer modelling predicted that the BA.2.86 mutations in Spike were likely to affect six of the ten most common epitopes (aminoacid sequences) recognised by T cells. However, this effect is mitigated by the large number of T cell epitopes distributed across the whole virus. Unlike neutralising antibodies, which target Spike, the viral protein that mutates the most, T cells recognize a broader range of viral proteins. This makes them more resilient to changes in the virus, offering protection against severe disease.
The first exposure matters
The study also showed that T-cell immunity is stronger in individuals who first encountered the virus through infection rather than vaccination, especially if it was the ancestral or the Delta variant. “Exposure to the whole virus, rather than just the Spike protein in vaccines, may result in a more robust and sustained T-cell immune response,” explains Gemma Moncunill, last author of the study. Finally, the researchers found no correlation between the strength of T-cell responses to Pirola, and the levels of binding or neutralising antibodies.
What this means for the future
The findings highlight the critical role of T cells in protecting us against COVID-19, especially as new variants emerge. While antibody responses are often the focus of vaccine development, these results suggest that boosting T cell immunity could be key to long-term protection.
Reference
Rubio R, Yavlinsky A, Escalera-Zamudio M et al. Initial antigen encounter determines robust T-cell immunity against SARS-CoV-2 BA.2.86 variant three years later. J of Infection. DOI: 10.1016/j.jinf.2024.106402
