Australian Study Find T Cells Responses In COVID-19 Patients Far From Optimal And At Low Levels Compared To Influenza Or Glandular Fever Infections
: Australian researchers from University of Melbourne, Monash University, La Trobe University, James Cook University and University of Tasmania have discovered that killer T cells, key immune cells in fighting viral infections, are present at much lower levels in individuals with COVID-19, compared to influenza or glandular fever.
As CD8+ T cell memory promotes rapid recovery the study team investigated circulating SARS-CoV-2−specific CD8+ T cells from COVID-19 patients. For two HLA-A*02:01 SARS-CoV-2−specific CD8+ T cell epitopes, the team found that, while ex vivo frequencies of responding T cells were approximately fivefold higher than for pre−COVID-19 samples, they were ∼10-fold lower than for influenza or EBV-specific memory CD8+ T cells.
Also these, SARS-CoV-2−specific CD8+ T cells recovered from convalescent COVID-19 patients had an atypically high prevalence of stem cell memory, central memory, and naïve phenotypes showing that they were not properly ‘primed’ to fight the virus. The team was not sure if this was as a result of the virus actions.
The study findings were published in the journal: Proceedings of National Academy of Sciences Of The United States Of America (PNAS) https://www.pnas.org/content/early/2020/09/09/2015486117
The study team led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute- University of Melbourne) looked at 22 COVID-19 samples from patients who experienced asymptomatic, mild or moderate illness.
Dr Jennifer Habel, first author from the University of Melbourne's Doherty Institute, said their research concentrated on CD8 T cells (killer T cells), which are integral to mounting an effective and rapid recovery from viruses such as influenza.
The study team looked at T cells in people who express a protein called human antigen leucocyte (HLA) serotype HLA-A2. HLA proteins are important for T cell recognition and vary across individuals.
Dr Habel told Thailand Medical News, "Surprisingly what we found is those key immune cells were not stimulated optimally for rapid proliferation and expansion to fight SAR-CoV-2.”
She further added, "The magnitude of the killer T cells was only five times higher than those of the naïve immune cells. To give that perspective, it is 10 times lower than what we see during an influenza or glandular fever response."
Further to the magnitude, the study team also looked at the activation profile of these immune cells and found that not only was activation poor, but in some cases these cells remained largely naïve, as if they hadn't been exposed to the virus at all.
Professor Dr Katherine Kedzierska, a laboratory head at the Doherty Institute-University of Melbourne and a world-leading influenza immunology researcher who led this study, said these striking findings support the 'prime and boost' vaccine model.’
Dr Kedzierska added, "Knowing the specific T cel
ls and proteins to target will inform the design of an effective vaccine. This research shows that potentially, if a vaccine was able to prime the immune system of killer T cells and then boost them a short time later, the immune response is likely to be much more robust to fight SARS-CoV2."
The research co-author, Doherty Institute Patron Laureate Professor Peter Doherty further added, "If the SARS-CoV-2 virus is indeed compromising the killer T cell response that can be important for recovery, the best bet may be to get the right vaccine before the virus gets to us."
It should be noted that none of the vaccine candidates currently in the phase 3 trials or are under development are adopting this strategy yet.
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