Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (8)

ORF1 (3)

ProteinS (3)

ORF3a (2)

ProteinM (1)


SARS-CoV-2 Proteins
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    Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV MESHD

    Authors: Aljawharah Alrubayyi; Ester Gea-Mallorqui; Emma Touizer; Dan Hameiri-Bowen; Jakub Kopycinski; Bethany Charlton; Narasha Fisher-Pearson; Luke Muir; Annachiara Rosa; Chloe Roustan; Christopher Earl; Peter Cherepanov; Pierre Pellegrino; Laura Waters; Fiona Burns; Sabine Kinloch; Tao Dong; Lucy Dorrell; Sarah Rowland-Jones; Laura E McCoy; Dimitra Peppa

    doi:10.1101/2021.02.15.431215 Date: 2021-02-16 Source: bioRxiv

    There is an urgent need to understand the nature of immune responses generated against SARS-CoV-2, to better inform risk-mitigation strategies for people living with HIV MESHD (PLWH). Although not all PLWH are considered immunosuppressed, residual cellular immune deficiency and ongoing inflammation MESHD could influence COVID-19 MESHD disease severity, the evolution and durability of protective memory responses. Here, we performed an integrated analysis, characterizing the nature, breadth and magnitude of SARS-CoV-2-specific immune responses in PLWH, controlled on ART, and HIV negative subjects. Both groups were in the convalescent phase of predominately mild COVID-19 MESHD disease. The majority of PLWH mounted SARS-CoV-2 Spike PROTEIN- and Nucleoprotein PROTEIN-specific antibodies with neutralizing activity and SARS-CoV-2-specific T cell responses, as measured by ELISpot, at levels comparable to HIV negative subjects. T cell responses against Spike, Membrane and Nucleocapsid were the most prominent, with SARS-CoV-2-specific CD4 HGNC T cells outnumbering CD8 HGNC T cells. Notably, the overall magnitude of SARS-CoV-2-specific T cell responses related to the size of the naive CD4 HGNC T cell pool and the CD4 HGNC: CD8 HGNC ratio in PLWH, in whom disparate antibody and T cell responses were observed. Both humoral and cellular responses to SARS-CoV-2 were detected at 5-7 months post-infection, providing evidence of medium-term durability of responses irrespective of HIV serostatus MESHD. Incomplete immune reconstitution on ART and a low CD4 HGNC: CD8 HGNC ratio could, however, hamper the development of immunity to SARS-CoV-2 and serve as a useful tool for risk stratification of PLWH. These findings have implications for the individual management and potential effectiveness of vaccination against SARS-CoV-2 in PLWH.

    Identification of Cross-Reactive CD8 HGNC+ T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants

    Authors: Chao Hu; Meiying Shen; XiaoJian Han; Qian Chen; Luo Li; Siyin Chen; Jing Zhang; Fengxia Gao; Wang Wang; Yingming Wang; Tingting Li; Shenglong Li; Jingjing Huang; Jianwei Wang; Ju Zhu; Dan Chen; Qingchen Wu; Kun Tao; Da Pang; Aishun Jin; Drew W. Barron-Kraus; Harrison C. Shrock; - UFCOVID Interventions Team; Justin Lessler; Carl D. Laird; Derek A.T. Cummings

    doi:10.1101/2020.11.02.364729 Date: 2020-11-03 Source: bioRxiv

    Despite the growing knowledge of T cell responses and their epitopes in COVID-19 MESHD patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Using a peptide library predicted with HLA class I-restriction, specific CD8 HGNC+ T cell responses were identified in over 75% of COVID-19 MESHD convalescent patients. Among the 15 SARS-CoV-2 epitopes identified from the S and N proteins PROTEIN, N361-369 (KTFPPTEPK) was the most dominant epitope. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity, and they exhibited complementary cross-reactivity to reported N361-369 mutant variants. In dendritic cells (DCs) and the lung organoid model, we found that the N361-369 epitope could be processed and endogenously presented to elicit the activation and cytotoxicity MESHD of CD8 HGNC+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, illuminating natural ways of viral clearance with high relevancy in the vaccine development.

    SARS-CoV-2 genome-wide mapping of CD8 HGNC T cell recognition reveals strong immunodominance and substantial CD8 HGNC T cell activation in COVID-19 MESHD patients

    Authors: Sunil Kumar Saini; Ditte Stampe Hersby; Tripti Tamhane; Helle Rus Povlsen; Susana Patricia Amaya Hernandez; Morten Nielsen; Anne Ortved Gang; Sine Reker Hadrup; Sergio Poli; Lance M. Peter; Chase J. Taylor; Jessica B. Blackburn; Bradley W. Richmond; Andrew G. Nicholson; Doris Rassl; William A. Wallace; Ivan O. Rosas; R. Gisli Jenkins; Naftali Kaminski; Jonathan A. Kropski; Nicholas E. Banovich; - Human Cell Atlas Lung Biological Network; Renata J Medeiros; Juliana MM Gomes; Mara Souza Junqueira; Katia Conceicao; Leticia G. Pontes; Antonio Condino Neto; Andrea C Perez; Leonardo G Barcellos; Jose Dias Correa Junior; Erick Gustavo Dorlass; Niels OS Camara; Edison Luiz Durigon; Fernando Q Cunha; Rafael H Nobrega; Glaucia M Machado-Santelli; Chuck S Farah; Flavio P Veras; Jorge Galindo-Villegas; Leticia Costa-Lotufo; Thiago M Cunha; Roger Chammas; Luciani R. Carvalho; Cristiane R. Guzzo; Ives Charlie-Silva

    doi:10.1101/2020.10.19.344911 Date: 2020-10-19 Source: bioRxiv

    To understand the CD8 HGNC+ T cell immunity related to viral protection and disease severity in COVID-19 MESHD, we evaluated the complete SARS-CoV-2 genome (3141 MHC-I binding peptides) to identify immunogenic T cell epitopes, and determine the level of CD8 HGNC+ T cell involvement using DNA-barcoded peptide-major histocompatibility complex (pMHC) multimers. COVID-19 MESHD patients showed strong T cell responses, with up to 25% of all CD8 HGNC+ lymphocytes specific to SARS-CoV-2-derived immunodominant epitopes, derived from ORF1 PROTEIN ( open reading frame 1 PROTEIN), ORF3 HGNC, and Nucleocapsid (N) protein PROTEIN. A strong signature of T cell activation was observed in COVID-19 MESHD patients, while no T cell activation was seen in the non-exposed and high exposure risk healthy donors. Interestingly, patients with severe disease displayed the largest T cell populations with a strong activation profile. These results will have important implications for understanding the T cell immunity to SARS-CoV-2 infection MESHD, and how T cell immunity might influence disease development.

    Antigenic variation of SARS-CoV-2 in response to immune pressure

    Authors: Diego Forni; Rachele Cagliani; Chiara Pontremoli; Alessandra Mozzi; Uberto Pozzoli; Mario Clerici; Manuela Sironi

    doi:10.1101/2020.07.15.204610 Date: 2020-07-15 Source: bioRxiv

    The ongoing evolution of SARS-CoV-2 is expected to be at least partially driven by the selective pressure imposed by the human immune system. We exploited the availability of a large number of high-quality SARS-CoV-2 genomes, as well as of validated epitope predictions, to show that B cell epitopes in the spike glycoprotein PROTEIN (S) and in the nucleocapsid protein (N PROTEIN) have higher diversity than non-epitope positions. Similar results were obtained for other human coronaviruses. Conversely, in the SARS-CoV-2 population, epitopes for CD4 HGNC+ and CD8 HGNC+ T cells were not more variable than non-epitope positions. A significant reduction in epitope variability was instead observed for some of the most immunogenic proteins (S PROTEIN, N, ORF8 PROTEIN, and ORF3a PROTEIN). Analysis over longer evolutionary time-frames indicated that this effect is not due to differential constraints. These data indicate that SARS-CoV-2 is evolving to elude the host humoral immune response, whereas recognition by T cells might benefit the virus.

    Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain: In silico analysis

    Authors: Onyeka S. Chukwudozie; Rebecca C Chukwuanukwu; Iroanya O. Onyekachi; Eze M. Daniel; Duru C. Vincent; Dele-Alimi T. Onaopemipo; Kehinde B. David; Bankole T. Taiwo; Obi C. Perpetua; Okinedo U. Elizabeth

    doi:10.1101/2020.06.30.176537 Date: 2020-07-01 Source: bioRxiv

    ABSTRACTThe novel coronavirus disease MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we, therefore, designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of nucleocapsid protein PROTEIN that aid in viral replication. Promising antigenic B-cells and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and non-allergenic property. Two CD8 HGNC+ and Three CD4 HGNC+ T-cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity MESHD, and putative restrictions to a number of MHC-I and II alleles. With these selected epitopes, a non-allergenic chimeric peptide vaccine incapable of inducing a Type II hypersensitivity reaction MESHD was constructed. The molecular interaction between the toll-like receptor-5 HGNC ( TLR5 HGNC) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.Competing Interest StatementThe authors have declared no competing interest.View Full Text

    Broad and strong memory CD4 HGNC+ and CD8 HGNC+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 MESHD patients.

    Authors: Tao Dong; Yanchun Peng; Alexander J Mentzer; Guihai Liu; Xuan Yao; Zixi Yin; Danning Dong; Wanwisa Dejnirattisai; Lance Turtle; Timothy Rostron; Krishanthi Subramaniam; Paul Thomson; Ping Zhang; Christina Dold; Jeremy Ratcliff; Thushan de Silva; Paul Sopp; Dannielle Wellington; Ushani Rajapaksa; Wayne Paes; Persephone Borrow; Benedikt M Kessler; Jeremy W Fry; Nikolai F Schwabe; Malcolm G Semple; J Kenneth Baillie; Peter JM Openshaw; Richard J Cornall; Chris Conlon; Gavin Screaton; Paul Klenerman; Juthathip Mongkolsapaya; Andrew McMichael; Julian C Knight; Graham Ogg; Peter Simmonds; Teresa Lockett; Robert Levin; Shona C Moore; Mariolina Salio; Giorgio Napolitani; Yi-Ling Chen; Susie Dunachie; Piyada Supasa; Chang Liu; Cesar Lopez-Camacho; Jose Slon-Campos; Yuguang Zhao; David I Stuart; Guido Paeson; Jonathan Grimes; Fred Antson; Oliver W Bayfield; Dorothy EDP Hawkins; De-Sheng Ker; Azim Ansari; Ellie Barnes; John Frater; Georgina Kerr; Philip Goulder

    doi:10.1101/2020.06.05.134551 Date: 2020-06-08 Source: bioRxiv

    COVID-19 MESHD is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19 MESHD, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFN{gamma} based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1 PROTEIN. We found the breadth, magnitude and frequency of memory T cell responses from COVID-19 MESHD were significantly higher in severe compared to mild COVID-19 MESHD cases, and this effect was most marked in response to spike, membrane, and ORF3a PROTEIN proteins. Total and spike-specific T cell responses correlated with the anti-Spike, anti-Receptor Binding Domain (RBD) as well as anti- Nucleoprotein PROTEIN (NP) endpoint antibody titre (p<0.001, <0.001 and =0.002). We identified 39 separate peptides containing CD4 HGNC+ and/or CD8 HGNC+ epitopes, which strikingly included six immunodominant epitope clusters targeted by T cells in many donors, including 3 clusters in spike (recognised by 29%, 24%, 18% donors), two in the membrane protein (M PROTEIN, 32%, 47%) and one in the nucleoprotein PROTEIN (Np, 35%). CD8 HGNC+ responses were further defined for their HLA restriction, including B*4001-restricted T cells showing central memory and effector memory MESHD phenotype. In mild cases, higher frequencies of multi-cytokine producing M- and NP-specific CD8 HGNC+ T cells than spike-specific CD8 HGNC+ T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8 HGNC+ to CD4 HGNC+ T cell responses. Immunodominant epitope clusters and peptides containing T cell epitopes identified in this study will provide critical tools to study the role of virus-specific T cells in control and resolution of SARS-CoV-2 infections MESHD. The identification of T cell specificity and functionality associated with milder disease, highlights the potential importance of including non- spike proteins PROTEIN within future COVID-19 MESHD vaccine design.

    Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals

    Authors: Nina Le Bert; Anthony Tanoto Tan; Kamini Kunasegaran; Christine Y. L. Tham; Morteza Hafezi; Adeline Chia; Melissa Chng; Meiyin Lin; Nicole Tan; Martin Linster; Wan Ni Chia; Mark I-Cheng Chen; Lin-Fa Wang; Eng Eong Ooi; Shirin Kalimuddin; Paul Anantharajal Tambyah; Jenny Guek-Hong Low; Yee-Joo Tan; Antonio Bertoletti

    doi:10.1101/2020.05.26.115832 Date: 2020-05-27 Source: bioRxiv

    Memory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural ( nucleocapsid protein PROTEIN, NP) and non-structural (NSP-7 and NSP13 PROTEIN of ORF1 PROTEIN) regions of SARS-CoV-2 in convalescent from COVID-19 MESHD (n=24). In all of them we demonstrated the presence of CD4 HGNC and CD8 HGNC T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 MESHD or contact with SARS/ COVID-19 MESHD patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 PROTEIN and 13, which were rarely detected in COVID-19 MESHD- and SARS-recovered patients. Epitope characterization of NSP7 PROTEIN-specific T cells showed recognition of protein fragments with low homology to "common cold" human coronaviruses but conserved among animal betacoranaviruses. Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection MESHD is of paramount importance for the management of the current COVID-19 pandemic MESHD.

    Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia ( NCP PROTEIN)

    Authors: Suxin Wan; Qingjie Yi; Shibing Fan; Jinglong Lv; Xianxiang Zhang; Lian Guo; Chunhui Lang; Qing Xiao; Kaihu Xiao; Zhengjun Yi; Mao Qiang; Jianglin Xiang; Bangshuo Zhang; Yongping Chen

    doi:10.1101/2020.02.10.20021832 Date: 2020-02-12 Source: medRxiv

    Background: To explore the cellular immunity and cytokines status of NCP PROTEIN patients and to predict the correlation between the cellular immunity levels, cytokines and the severity of patients. Methods: 123 NCP PROTEIN patients were divided into mild and severe groups. Peripheral blood was collected, lymphocyte subsets and cytokines were detected. Correlation analysis was performed on the lymphocyte subsets and cytokines, and the differences between the indexes of the two groups were analyzed. Results: 102 mild and 21 severe patients were included. Lymphocyte subsets were reduced in two groups. The proportion of CD8 HGNC + T reduction in the mild and severe group was 28.43% and 61.9%, respectively; The proportion of B cell reduction was 25.49% and 28.57%; The proportion of NK cell reduction was 34.31% and 47.62%; The detection value of IL-6 HGNC was 0 in 55.88% of the mild group, mild group has a significantly lower proportion of patients with IL-6 HGNC higher than normal than severe group; There was no significant linear correlation between the lymphocyte subsets and cytokines, while significant differences were noticed between the two groups in CD4 HGNC + T, CD8 HGNC + T, IL-6 HGNC and IL-10 HGNC. Conclusions: Low levels of CD4 HGNC+T and CD8 HGNC+T are common in severe NCP PROTEIN. IL-6 HGNC and IL-10 HGNC levels were higher in severe patients. T cell subsets and cytokines can be used as one of the basis for predicting the transition from mild to severe. Large number of samples are still needed to confirm the "warning value" of CD4 HGNC + T, CD8 HGNC + T IL-6 HGNC and IL-10 HGNC.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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