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  1. Article ; Online: SARS-CoV-2-induced humoral immunity through B cell epitope analysis in COVID-19 infected individuals.

    Yoshida, Shota / Ono, Chikako / Hayashi, Hiroki / Fukumoto, Shinya / Shiraishi, Satoshi / Tomono, Kazunori / Arase, Hisashi / Matsuura, Yoshiharu / Nakagami, Hironori

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 5934

    Abstract: The aim of this study is to understand adaptive immunity to SARS-CoV-2 through the analysis of B ... cell epitope and neutralizing activity in coronavirus disease 2019 (COVID-19) patients. We obtained ... but not IgM, antibody titer of COVID-19 patients. In the analysis of the predicted the linear B cell ...

    Abstract The aim of this study is to understand adaptive immunity to SARS-CoV-2 through the analysis of B cell epitope and neutralizing activity in coronavirus disease 2019 (COVID-19) patients. We obtained serum from forty-three COVID-19 patients from patients in the intensive care unit of Osaka University Hospital (n = 12) and in Osaka City Juso Hospital (n = 31). Most individuals revealed neutralizing activity against SARS-CoV-2 assessed by a pseudotype virus-neutralizing assay. The antibody production against the spike glycoprotein (S protein) or receptor-binding domain (RBD) of SARS-CoV-2 was elevated, with large individual differences, as assessed by ELISA. We observed the correlation between neutralizing antibody titer and IgG, but not IgM, antibody titer of COVID-19 patients. In the analysis of the predicted the linear B cell epitopes, hot spots in the N-terminal domain of the S protein were observed in the serum from patients in the intensive care unit of Osaka University Hospital. Overall, the analysis of antibody production and B cell epitopes of the S protein from patient serum may provide a novel target for the vaccine development against SARS-CoV-2.
    MeSH term(s) Amino Acid Sequence ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/virology ; Enzyme-Linked Immunosorbent Assay ; Epitopes, B-Lymphocyte/immunology ; Female ; Host-Pathogen Interactions ; Humans ; Immunity, Humoral ; Male ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/immunology
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes, B-Lymphocyte ; Spike Glycoprotein, Coronavirus
    Language English
    Publishing date 2021-03-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-85202-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SARS-CoV-2-induced humoral immunity through B cell epitope analysis in COVID-19 infected individuals

    Shota Yoshida / Chikako Ono / Hiroki Hayashi / Shinya Fukumoto / Satoshi Shiraishi / Kazunori Tomono / Hisashi Arase / Yoshiharu Matsuura / Hironori Nakagami

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: ... through the analysis of B cell epitope and neutralizing activity in coronavirus disease 2019 (COVID-19) patients ... but not IgM, antibody titer of COVID-19 patients. In the analysis of the predicted the linear B cell ... Abstract The aim of this study is to understand adaptive immunity to SARS-CoV-2 ...

    Abstract Abstract The aim of this study is to understand adaptive immunity to SARS-CoV-2 through the analysis of B cell epitope and neutralizing activity in coronavirus disease 2019 (COVID-19) patients. We obtained serum from forty-three COVID-19 patients from patients in the intensive care unit of Osaka University Hospital (n = 12) and in Osaka City Juso Hospital (n = 31). Most individuals revealed neutralizing activity against SARS-CoV-2 assessed by a pseudotype virus-neutralizing assay. The antibody production against the spike glycoprotein (S protein) or receptor-binding domain (RBD) of SARS-CoV-2 was elevated, with large individual differences, as assessed by ELISA. We observed the correlation between neutralizing antibody titer and IgG, but not IgM, antibody titer of COVID-19 patients. In the analysis of the predicted the linear B cell epitopes, hot spots in the N-terminal domain of the S protein were observed in the serum from patients in the intensive care unit of Osaka University Hospital. Overall, the analysis of antibody production and B cell epitopes of the S protein from patient serum may provide a novel target for the vaccine development against SARS-CoV-2.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: SARS-CoV-2-induced humoral immunity through B cell epitope analysis and neutralizing activity in COVID-19 infected individuals in Japan

    Yoshida, Shota / Ono, Chikako / Hayashi, Hiroki / Shiraishi, Satoshi / Tomono, Kazunori / Arase, Hisashi / Matsuura, Yoshiharu / Nakagami, Hironori

    bioRxiv

    Abstract: The aim of this study is to understand adaptive immunity to SARS-CoV-2 through the analysis of B ... serum from thirteen COVID-19 patients. Most individuals revealed neutralizing activity against SARS-CoV ... cell epitope and neutralizing activity in coronavirus disease 2019 (COVID-19) patients. We obtained ...

    Abstract The aim of this study is to understand adaptive immunity to SARS-CoV-2 through the analysis of B cell epitope and neutralizing activity in coronavirus disease 2019 (COVID-19) patients. We obtained serum from thirteen COVID-19 patients. Most individuals revealed neutralizing activity against SARS-CoV-2 assessed by a pseudotype virus-neutralizing assay. The antibody production against the spike glycoprotein (S protein) or receptor-binding domain (RBD) of SARS-CoV-2 was elevated, with large individual differences, as assessed by ELISA. In the analysis of the predicted the linear B cell epitopes, two regions (671-690 aa. and 1146-1164 aa.), which were located in S1 and S2 but not in the RBD, were highly reactive with the sera from patients. In the further analysis of the B cell epitope within the S protein by utilizing a B cell epitope array, a hot spot in the N-terminal domain of the S protein but not the RBD was observed in individuals with neutralizing activity. Overall, the analysis of antibody production and B cell epitopes of the S protein from patient serum may provide a novel target for the vaccine development against SARS-CoV-2.
    Keywords covid19
    Publisher BioRxiv; WHO
    Document type Article ; Online
    DOI 10.1101/2020.07.22.212761
    Database COVID19

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  4. Article ; Online: SARS-CoV-2-induced humoral immunity through B cell epitope analysis and neutralizing activity in COVID-19 infected individuals in Japan

    Yoshida, Shota / Ono, Chikako / Hayashi, Hiroki / Shiraishi, Satoshi / Kazunori, Tomono / Arase, Hisashi / Matsuura, Yoshiharu / Nakagami, Hironori

    bioRxiv

    Abstract: The aim of this study is to understand adaptive immunity to SARS-CoV-2 through the analysis of B ... serum from thirteen COVID-19 patients. Most individuals revealed neutralizing activity against SARS-CoV ... cell epitope and neutralizing activity in coronavirus disease 2019 (COVID-19) patients. We obtained ...

    Abstract The aim of this study is to understand adaptive immunity to SARS-CoV-2 through the analysis of B cell epitope and neutralizing activity in coronavirus disease 2019 (COVID-19) patients. We obtained serum from thirteen COVID-19 patients. Most individuals revealed neutralizing activity against SARS-CoV-2 assessed by a pseudotype virus-neutralizing assay. The antibody production against the spike glycoprotein (S protein) or receptor-binding domain (RBD) of SARS-CoV-2 was elevated, with large individual differences, as assessed by ELISA. In the analysis of the predicted the linear B cell epitopes, two regions (671-690 aa. and 1146-1164 aa.), which were located in S1 and S2 but not in the RBD, were highly reactive with the sera from patients. In the further analysis of the B cell epitope within the S protein by utilizing a B cell epitope array, a hot spot in the N-terminal domain of the S protein but not the RBD was observed in individuals with neutralizing activity. Overall, the analysis of antibody production and B cell epitopes of the S protein from patient serum may provide a novel target for the vaccine development against SARS-CoV-2.
    Keywords covid19
    Language English
    Publishing date 2020-07-23
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.07.22.212761
    Database COVID19

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  5. Article ; Online: Multiparametric analysis of the specific immune response against SARS-CoV-2.

    Vránová, Lucie / Poláková, Ingrid / Vaníková, Šárka / Saláková, Martina / Musil, Jan / Vaníčková, Marie / Vencálek, Ondřej / Holub, Michal / Bohoněk, Miloš / Řezáč, David / Dresler, Jiří / Tachezy, Ruth / Šmahel, Michal

    Infectious diseases (London, England)

    2024  , Page(s) 1–19

    Abstract: Background: SARS-CoV-2, which causes COVID-19, has killed more than 7 million people worldwide ... We confirmed that SARS-CoV-2 infection induces the establishment of long-term memory IgG: Conclusion ... long-term perturbation of the overall antiviral immune response caused by SARS-CoV-2 infection. ...

    Abstract Background: SARS-CoV-2, which causes COVID-19, has killed more than 7 million people worldwide. Understanding the development of postinfectious and postvaccination immune responses is necessary for effective treatment and the introduction of appropriate antipandemic measures.
    Objectives: We analysed humoral and cell-mediated anti-SARS-CoV-2 immune responses to spike (S), nucleocapsid (N), membrane (M), and open reading frame (O) proteins in individuals collected up to 1.5 years after COVID-19 onset and evaluated immune memory.
    Methods: Peripheral blood mononuclear cells and serum were collected from patients after COVID-19. Sampling was performed in two rounds: 3-6 months after infection and after another year. Most of the patients were vaccinated between samplings. SARS-CoV-2-seronegative donors served as controls. ELISpot assays were used to detect SARS-CoV-2-specific T and B cells using peptide pools (S, NMO) or recombinant proteins (rS, rN), respectively. A CEF peptide pool consisting of selected viral epitopes was applied to assess the antiviral T-cell response. SARS-CoV-2-specific antibodies were detected
    Results: We confirmed that SARS-CoV-2 infection induces the establishment of long-term memory IgG
    Conclusion: This study supports the importance of repeated vaccination for enhancing immunity and suggests a possible long-term perturbation of the overall antiviral immune response caused by SARS-CoV-2 infection.
    Language English
    Publishing date 2024-05-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2839775-7
    ISSN 2374-4243 ; 2374-4235
    ISSN (online) 2374-4243
    ISSN 2374-4235
    DOI 10.1080/23744235.2024.2358379
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Single-cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine.

    Sureshchandra, Suhas / Lewis, Sloan A / Doratt, Brianna M / Jankeel, Allen / Coimbra Ibraim, Izabela / Messaoudi, Ilhem

    JCI insight

    2021  Volume 6, Issue 24

    Abstract: mRNA vaccines for SARS-CoV-2 have shown exceptional clinical efficacy, providing robust protection ... cellular responses to 2 doses of mRNA vaccine with responses observed in convalescent individuals ... the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion ...

    Abstract mRNA vaccines for SARS-CoV-2 have shown exceptional clinical efficacy, providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used scRNA-Seq and functional assays to compare humoral and cellular responses to 2 doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4+ T cells, and robust antigen-specific polyfunctional CD4+ T cell responses following vaccination. On the other hand, although clonally expanded CD8+ T cells were observed following both vaccination and natural infection, CD8+ T cell responses were relatively weak and variable. In addition, TCR gene usage was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of CD8+ T cell clones that occupy distinct clusters compared to those induced by vaccination and likely recognize a broader set of viral antigens of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response in which early CD4+ T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8+ T cells, together capable of contributing to future recall responses.
    MeSH term(s) 2019-nCoV Vaccine mRNA-1273/immunology ; 2019-nCoV Vaccine mRNA-1273/therapeutic use ; Adaptive Immunity/genetics ; Adaptive Immunity/immunology ; Adult ; Aged ; Antigens, Viral ; B-Lymphocytes ; BNT162 Vaccine/immunology ; BNT162 Vaccine/therapeutic use ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; COVID-19 Vaccines/therapeutic use ; Carrier State ; Convalescence ; Epitopes ; Female ; Humans ; Immunity, Cellular/genetics ; Immunity, Cellular/immunology ; Immunity, Humoral/genetics ; Immunity, Humoral/immunology ; Immunogenicity, Vaccine ; Immunologic Memory ; Male ; Middle Aged ; RNA-Seq ; SARS-CoV-2 ; Single-Cell Analysis ; Spike Glycoprotein, Coronavirus/immunology ; Th1 Cells ; Th17 Cells ; Vaccines, Synthetic/immunology ; Vaccines, Synthetic/therapeutic use ; Young Adult ; mRNA Vaccines/immunology ; mRNA Vaccines/therapeutic use
    Chemical Substances Antigens, Viral ; COVID-19 Vaccines ; Epitopes ; Spike Glycoprotein, Coronavirus ; Vaccines, Synthetic ; mRNA Vaccines ; spike protein, SARS-CoV-2 ; 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; BNT162 Vaccine (N38TVC63NU)
    Language English
    Publishing date 2021-12-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.153201
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Sequence-based prediction of SARS-CoV-2 vaccine targets using a mass spectrometry-based bioinformatics predictor identifies immunogenic T cell epitopes.

    Poran, Asaf / Harjanto, Dewi / Malloy, Matthew / Arieta, Christina M / Rothenberg, Daniel A / Lenkala, Divya / van Buuren, Marit M / Addona, Terri A / Rooney, Michael S / Srinivasan, Lakshmi / Gaynor, Richard B

    Genome medicine

    2020  Volume 12, Issue 1, Page(s) 70

    Abstract: ... for protective immunity against SARS-CoV-2. Early reports identify protective roles for both humoral and ... epitopes from SARS-CoV-2 proteins. We assayed a subset of these epitopes in a T cell induction assay ... cell-mediated immunity for SARS-CoV-2.: Methods: We leveraged our bioinformatics binding prediction tools for human ...

    Abstract Background: The ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Early reports identify protective roles for both humoral and cell-mediated immunity for SARS-CoV-2.
    Methods: We leveraged our bioinformatics binding prediction tools for human leukocyte antigen (HLA)-I and HLA-II alleles that were developed using mass spectrometry-based profiling of individual HLA-I and HLA-II alleles to predict peptide binding to diverse allele sets. We applied these binding predictors to viral genomes from the Coronaviridae family and specifically focused on T cell epitopes from SARS-CoV-2 proteins. We assayed a subset of these epitopes in a T cell induction assay for their ability to elicit CD8
    Results: We first validated HLA-I and HLA-II predictions on Coronaviridae family epitopes deposited in the Virus Pathogen Database and Analysis Resource (ViPR) database. We then utilized our HLA-I and HLA-II predictors to identify 11,897 HLA-I and 8046 HLA-II candidate peptides which were highly ranked for binding across 13 open reading frames (ORFs) of SARS-CoV-2. These peptides are predicted to provide over 99% allele coverage for the US, European, and Asian populations. From our SARS-CoV-2-predicted peptide-HLA-I allele pairs, 374 pairs identically matched what was previously reported in the ViPR database, originating from other coronaviruses with identical sequences. Of these pairs, 333 (89%) had a positive HLA binding assay result, reinforcing the validity of our predictions. We then demonstrated that a subset of these highly predicted epitopes were immunogenic based on their recognition by specific CD8
    Conclusions: Using our bioinformatics platform, we identify multiple putative epitopes that are potential targets for CD4
    MeSH term(s) Alleles ; Antibody Affinity ; COVID-19 ; COVID-19 Vaccines ; Computational Biology ; Coronavirus Infections/genetics ; Coronavirus Infections/immunology ; Coronavirus Infections/prevention & control ; Epitopes/chemistry ; Epitopes/genetics ; Epitopes/immunology ; Genome, Viral ; HLA Antigens/chemistry ; HLA Antigens/genetics ; HLA Antigens/immunology ; Humans ; Immunogenicity, Vaccine ; Mass Spectrometry ; Pandemics ; Pneumonia, Viral/immunology ; T-Lymphocytes/immunology ; Viral Vaccines/chemistry ; Viral Vaccines/genetics ; Viral Vaccines/immunology
    Chemical Substances COVID-19 Vaccines ; Epitopes ; HLA Antigens ; Viral Vaccines
    Keywords covid19
    Language English
    Publishing date 2020-08-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-020-00767-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Sequence-based prediction of SARS-CoV-2 vaccine targets using a mass spectrometry-based bioinformatics predictor identifies immunogenic T cell epitopes

    Asaf Poran / Dewi Harjanto / Matthew Malloy / Christina M. Arieta / Daniel A. Rothenberg / Divya Lenkala / Marit M. van Buuren / Terri A. Addona / Michael S. Rooney / Lakshmi Srinivasan / Richard B. Gaynor

    Genome Medicine, Vol 12, Iss 1, Pp 1-

    2020  Volume 15

    Abstract: ... for both humoral and cell-mediated immunity for SARS-CoV-2. Methods We leveraged our bioinformatics binding ... mononuclear cells (PBMCs). Finally, we characterized the expression of SARS-CoV-2 proteins in virally infected ... specifically focused on T cell epitopes from SARS-CoV-2 proteins. We assayed a subset of these epitopes in a T ...

    Abstract Abstract Background The ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Early reports identify protective roles for both humoral and cell-mediated immunity for SARS-CoV-2. Methods We leveraged our bioinformatics binding prediction tools for human leukocyte antigen (HLA)-I and HLA-II alleles that were developed using mass spectrometry-based profiling of individual HLA-I and HLA-II alleles to predict peptide binding to diverse allele sets. We applied these binding predictors to viral genomes from the Coronaviridae family and specifically focused on T cell epitopes from SARS-CoV-2 proteins. We assayed a subset of these epitopes in a T cell induction assay for their ability to elicit CD8+ T cell responses. Results We first validated HLA-I and HLA-II predictions on Coronaviridae family epitopes deposited in the Virus Pathogen Database and Analysis Resource (ViPR) database. We then utilized our HLA-I and HLA-II predictors to identify 11,897 HLA-I and 8046 HLA-II candidate peptides which were highly ranked for binding across 13 open reading frames (ORFs) of SARS-CoV-2. These peptides are predicted to provide over 99% allele coverage for the US, European, and Asian populations. From our SARS-CoV-2-predicted peptide-HLA-I allele pairs, 374 pairs identically matched what was previously reported in the ViPR database, originating from other coronaviruses with identical sequences. Of these pairs, 333 (89%) had a positive HLA binding assay result, reinforcing the validity of our predictions. We then demonstrated that a subset of these highly predicted epitopes were immunogenic based on their recognition by specific CD8+ T cells in healthy human donor peripheral blood mononuclear cells (PBMCs). Finally, we characterized the expression of SARS-CoV-2 proteins in virally infected cells to prioritize those which could be potential targets for T cell immunity. Conclusions Using our bioinformatics platform, we identify multiple putative epitopes that are ...
    Keywords COVID-19 ; SARS-CoV-2 T cell epitopes ; Computational biology ; HLA-I binding prediction ; HLA-II binding prediction ; T cell assay ; Medicine ; R ; Genetics ; QH426-470 ; covid19
    Subject code 570
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Sequence-based prediction of SARS-CoV-2 vaccine targets using a mass spectrometry-based bioinformatics predictor identifies immunogenic T cell epitopes

    Poran, Asaf / Harjanto, Dewi / Malloy, Matthew / Arieta, Christina M / Rothenberg, Daniel A / Lenkala, Divya / van Buuren, Marit M / Addona, Terri A / Rooney, Michael S / Srinivasan, Lakshmi / Gaynor, Richard B

    Genome Med

    Abstract: ... we characterized the expression of SARS-CoV-2 proteins in virally infected cells to prioritize those which could be ... for protective immunity against SARS-CoV-2. Early reports identify protective roles for both humoral and ... epitopes from SARS-CoV-2 proteins. We assayed a subset of these epitopes in a T cell induction assay ...

    Abstract BACKGROUND: The ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Early reports identify protective roles for both humoral and cell-mediated immunity for SARS-CoV-2. METHODS: We leveraged our bioinformatics binding prediction tools for human leukocyte antigen (HLA)-I and HLA-II alleles that were developed using mass spectrometry-based profiling of individual HLA-I and HLA-II alleles to predict peptide binding to diverse allele sets. We applied these binding predictors to viral genomes from the Coronaviridae family and specifically focused on T cell epitopes from SARS-CoV-2 proteins. We assayed a subset of these epitopes in a T cell induction assay for their ability to elicit CD8+ T cell responses. RESULTS: We first validated HLA-I and HLA-II predictions on Coronaviridae family epitopes deposited in the Virus Pathogen Database and Analysis Resource (ViPR) database. We then utilized our HLA-I and HLA-II predictors to identify 11,897 HLA-I and 8046 HLA-II candidate peptides which were highly ranked for binding across 13 open reading frames (ORFs) of SARS-CoV-2. These peptides are predicted to provide over 99% allele coverage for the US, European, and Asian populations. From our SARS-CoV-2-predicted peptide-HLA-I allele pairs, 374 pairs identically matched what was previously reported in the ViPR database, originating from other coronaviruses with identical sequences. Of these pairs, 333 (89%) had a positive HLA binding assay result, reinforcing the validity of our predictions. We then demonstrated that a subset of these highly predicted epitopes were immunogenic based on their recognition by specific CD8+ T cells in healthy human donor peripheral blood mononuclear cells (PBMCs). Finally, we characterized the expression of SARS-CoV-2 proteins in virally infected cells to prioritize those which could be potential targets for T cell immunity. CONCLUSIONS: Using our bioinformatics platform, we identify multiple putative epitopes that are potential targets for CD4+ and CD8+ T cells, whose HLA binding properties cover nearly the entire population. We also confirm that our binding predictors can predict epitopes eliciting CD8+ T cell responses from multiple SARS-CoV-2 proteins. Protein expression and population HLA allele coverage, combined with the ability to identify T cell epitopes, should be considered in SARS-CoV-2 vaccine design strategies and immune monitoring.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #714063
    Database COVID19

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