Understanding T cell immunity against SARS-CoV-2, the causative pathogen of COVID-19, can assist in the development of efficacious vaccines and novel diagnostic technologies.
A thorough understanding of the epitopic targets of SARS-CoV-2 by T cells in recovered individuals could also help us to determine their cross-reactivity against novel SARS-CoV-2 variants of concern (VoC), which exhibit important genetic mutations at the viral spike protein (the main antigenic target for most COVID-19 vaccines).
New research by a team of scientists at The Hong Kong University of Science and Technology sheds light on the epitopic targets of SARS-CoV-2 by T cells in COVID-19 convalescents. The team’s findings suggest that the epitopes targeted by T cells during infection may not be affected by the emergence of SARS-CoV-2 variants.
To arrive at these findings, the scientists undertook a meta-analysis of SARS-CoV-2 T cell epitopes from eighteen studies, including cohorts of recovering COVID-19 patients, enabling them to analyze an overall sample size of 852 patients.
They observed results from patients from a wide variety of areas, across four continents, including a range of different ages, both sexes, disease severities and blood collection times. The team reported their findings in the scientific journal Cell Reports Medicine.
T-cell Responses over time
Studies of convalescent or recovering COVID-19 patients have shown that SARS-CoV-2-specific T cells can be detected up to nine months post-infection, which offers insight into the potential of T cells to provide longer-lasting immunity after neutralizing antibodies begin to wane. With different discussions about how long T cell immunity can last after SARS-CoV-2 infection, and the bearing this has on our ability to arrest the COVID-19 pandemic, research into this area is incredibly important.
Antibody responses are also a subject of concern regarding the longevity of SARS-CoV-2 immunity, as they have been reported to decline within a few months post-infection. Additionally, when other closely related human coronaviruses like SARS-CoV have been examined, specific T cells have been shown to remain in the body for up to 17 years post-infection. Meanwhile, evidence suggests that corresponding antibody responses to SARS-CoV are only present for up to a few years. By analyzing the SARS-CoV-2 infection, as well as considering the effects in similar viruses, a predictable immune response can be estimated and aid in the development and administration of immune-boosting prophylactics.
By characterizing the SARS-CoV-2 T cell epitopes and human leucocyte antigen (HLA) association, the researchers provide insightful information on the expected T cell response after both vaccine- and infection-induced immunity.
These can also help to assist research into populations of specific ethnicities or those in specific geographic areas with prevalent HLA alleles which would react to the infection and the immunity that would go along with that. Understanding any geographical or ethnicity-related differences in immune responses can help healthcare systems provide targeted support and meet specific treatment needs where needed.
The significance of this research is that it could assess the T cell responses induced by the COVID-19, which mainly focus on the viral spike protein, as well as provide insight into how the immune response can be boosted in those who are less likely to respond to the infection effectively.
Professor Ahmed Abdul Quadeer, the first author of the study, from the Department of Electronic and Computer Engineering, commented that the focus of the scientists consisted of being "specifically on recovered COVID-19 patients as their immune responses are representative of effective responses against the virus."
The research group uncovered more than 700 T cell epitopes, as well as twenty specific immunoprevalent epitopes that induced the T cell response in the sample size analyzed.
They also found that although antibody responses can be more affected by variants, the T cell responses still seem to hold up against genetic mutations of the virus. Professor Mathew Mckay, who co-led this research, believes this is "good news, particularly for vaccines," as "assuming that vaccines mimic [responses] of natural infection," then the T cell response can be more safely assumed to be relied upon even amid emerging variants.
This analysis undertaken by these researchers looked at a range of recovering COVID-19 patients and found that the T cell response remained more or less consistent in the sample population, regardless of SARS-CoV-2 variants. The data was integrated into a web platform which the scientists plan to update with further information as their research into the virus T-cell epitopes continues, advancing the knowledge of this disease steadily.
Professor Quadeer hopes this platform can be used as an online resource globally for researchers worldwide, enabling further understanding of the T cell responses against the virus. He is anticipating that this can help to aid further studies with his team providing a stepping stone and basis for other researchers to build upon for the advancement into COVID-19 vaccines and diagnostics.
- Quadeer, A.A., Ahmed, S.F., McKay, M.R., Landscape of epitopes targeted by T cells in 852 convalescent COVID-19 patients: Meta-analysis, immunoprevalence and web platform, Cell Reports Medicine (2021), DOI: https://doi.org/10.1016/j.xcrm.2021.100312, https://www.sciencedirect.com/science/article/pii/S2666379121001555