This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Juliane S. Walz
Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6404-7391
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SARS-CoV-2, the virus causing COVID-19, has dramatically altered life around the globe. For antiviral therapeutics like vaccines to work, scientists need to know which areas of the virus - or epitopes - can activate immune cells called T cells. The authors of this study used computer algorithms to predict which epitopes of SARS-CoV-2 could activate T cells. To confirm those predictions, they measured how T cells responded using blood samples from two groups of people: 180 individuals previously infected with SARS-CoV-2 and 185 individuals not exposed to the virus. The team discovered that some epitopes were specific to SARS-CoV-2, while others were cross-reactive—they were similar enough to epitopes on common-cold-causing viruses to prompt a T-cell response. In fact, 81% of unexposed individuals had some T-cell response to these epitopes. While this suggests at least some built-in immune protection from SARS-CoV-2, T-cell responses in previously infected people were much more robust than those in unexposed individuals. Individuals with a broader T-cell response to viral epitopes reported less-severe COVID-19 symptoms, suggesting that people with some T-cell recognition of SARS-CoV-2 prior to infection may exhibit less severe illness. Additional studies comparing the same subjects before and after infection are needed to understand how T-cell cross-reactivity relates to immunity and symptom severity. Nevertheless, this study suggests that promoting T-cell responses to SARS-CoV-2 may be important for designing effective therapeutic and preventive measures.
View Research Highlight
The SARS-CoV-2 pandemic calls for the rapid development of diagnostic, preventive, and therapeutic approaches. CD4+ and CD8+ T cell-mediated immunity is central for control of and protection from viral infections[1-3]. A prerequisite to characterize T-cell immunity, but also for the development of vaccines and immunotherapies, is the identification of the exact viral T-cell epitopes presented on human leukocyte antigens (HLA)[2-8]. This is the first work identifying and characterizing SARS-CoV-2-specific and cross-reactive HLA class I and HLA-DR T-cell epitopes in SARS-CoV-2 convalescents (n = 180) as well as unexposed individuals (n = 185) and confirming their relevance for immunity and COVID-19 disease course. SARS-CoV-2-specific T-cell epitopes enabled detection of post-infectious T-cell immunity, even in seronegative convalescents. Cross-reactive SARS-CoV-2 T-cell epitopes revealed preexisting T-cell responses in 81% of unexposed individuals, and validation of similarity to common cold human coronaviruses provided a functional basis for postulated heterologous immunity[9] in SARS-CoV-2 infection[10,11]. Intensity of T-cell responses and recognition rate of T-cell epitopes was significantly higher in the convalescent donors compared to unexposed individuals, suggesting that not only expansion, but also diversity spread of SARS-CoV-2 T-cell responses occur upon active infection. Whereas anti-SARS-CoV-2 antibody levels were associated with severity of symptoms in our SARS-CoV-2 donors, intensity of T-cell responses did not negatively affect COVID-19 severity. Rather, diversity of SARS-CoV-2 T-cell responses was increased in case of mild symptoms of COVID-19, providing evidence that development of immunity requires recognition of multiple SARS-CoV-2 epitopes. Together, the specific and cross-reactive SARS-CoV-2 T-cell epitopes identified in this work enable the identification of heterologous and post-infectious T-cell immunity and facilitate the development of diagnostic, preventive, and therapeutic measures for COVID-19.
Keywords
SARS-CoV-2, COVID-19, T-cell epitopes, HLA peptides, vaccine design, T-cells, immunity
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Juliane S. Walz
Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6404-7391
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Nature Immunology.
Version 1
Posted 16 Jun, 2020
Community comments: 12
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Nature Immunology.
View Research Highlight
Research Highlight
created by Research Square
SARS-CoV-2, the virus causing COVID-19, has dramatically altered life around the globe. For antiviral therapeutics like vaccines to work, scientists need to know which areas of the virus - or epitopes - can activate immune cells called T cells. The authors of this study used computer algorithms to predict which epitopes of SARS-CoV-2 could activate T cells. To confirm those predictions, they measured how T cells responded using blood samples from two groups of people: 180 individuals previously infected with SARS-CoV-2 and 185 individuals not exposed to the virus. The team discovered that some epitopes were specific to SARS-CoV-2, while others were cross-reactive—they were similar enough to epitopes on common-cold-causing viruses to prompt a T-cell response. In fact, 81% of unexposed individuals had some T-cell response to these epitopes. While this suggests at least some built-in immune protection from SARS-CoV-2, T-cell responses in previously infected people were much more robust than those in unexposed individuals. Individuals with a broader T-cell response to viral epitopes reported less-severe COVID-19 symptoms, suggesting that people with some T-cell recognition of SARS-CoV-2 prior to infection may exhibit less severe illness. Additional studies comparing the same subjects before and after infection are needed to understand how T-cell cross-reactivity relates to immunity and symptom severity. Nevertheless, this study suggests that promoting T-cell responses to SARS-CoV-2 may be important for designing effective therapeutic and preventive measures.
View Research Highlight
The SARS-CoV-2 pandemic calls for the rapid development of diagnostic, preventive, and therapeutic approaches. CD4+ and CD8+ T cell-mediated immunity is central for control of and protection from viral infections[1-3]. A prerequisite to characterize T-cell immunity, but also for the development of vaccines and immunotherapies, is the identification of the exact viral T-cell epitopes presented on human leukocyte antigens (HLA)[2-8]. This is the first work identifying and characterizing SARS-CoV-2-specific and cross-reactive HLA class I and HLA-DR T-cell epitopes in SARS-CoV-2 convalescents (n = 180) as well as unexposed individuals (n = 185) and confirming their relevance for immunity and COVID-19 disease course. SARS-CoV-2-specific T-cell epitopes enabled detection of post-infectious T-cell immunity, even in seronegative convalescents. Cross-reactive SARS-CoV-2 T-cell epitopes revealed preexisting T-cell responses in 81% of unexposed individuals, and validation of similarity to common cold human coronaviruses provided a functional basis for postulated heterologous immunity[9] in SARS-CoV-2 infection[10,11]. Intensity of T-cell responses and recognition rate of T-cell epitopes was significantly higher in the convalescent donors compared to unexposed individuals, suggesting that not only expansion, but also diversity spread of SARS-CoV-2 T-cell responses occur upon active infection. Whereas anti-SARS-CoV-2 antibody levels were associated with severity of symptoms in our SARS-CoV-2 donors, intensity of T-cell responses did not negatively affect COVID-19 severity. Rather, diversity of SARS-CoV-2 T-cell responses was increased in case of mild symptoms of COVID-19, providing evidence that development of immunity requires recognition of multiple SARS-CoV-2 epitopes. Together, the specific and cross-reactive SARS-CoV-2 T-cell epitopes identified in this work enable the identification of heterologous and post-infectious T-cell immunity and facilitate the development of diagnostic, preventive, and therapeutic measures for COVID-19.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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