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1.
Genome Med ; 12(1): 70, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32791978

RESUMO

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.


Assuntos
Infecções por Coronavirus/imunologia , Epitopos/imunologia , Antígenos HLA/imunologia , Pneumonia Viral/imunologia , Linfócitos T/imunologia , Vacinas Virais/imunologia , Alelos , Afinidade de Anticorpos , Biologia Computacional , Infecções por Coronavirus/genética , Infecções por Coronavirus/prevenção & controle , Epitopos/química , Epitopos/genética , Genoma Viral , Antígenos HLA/química , Antígenos HLA/genética , Humanos , Imunogenicidade da Vacina , Espectrometria de Massas , Pandemias , Vacinas Virais/química , Vacinas Virais/genética
2.
Front Immunol ; 11: 1663, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754160

RESUMO

A recent pandemic caused by a single-stranded RNA virus, COVID-19, initially discovered in China, is now spreading globally. This poses a serious threat that needs to be addressed immediately. Genome analysis of SARS-CoV-2 has revealed its close relation to SARS-coronavirus along with few changes in its spike protein. The spike protein aids in receptor binding and viral entry within the host and therefore represents a potential target for vaccine and therapeutic development. In the current study, the spike protein of SARS-CoV-2 was explored for potential immunogenic epitopes to design multi-epitope vaccine constructs. The S1 and S2 domains of spike proteins were analyzed, and two vaccine constructs were prioritized with T-cell and B-cell epitopes. We adapted a comprehensive predictive framework to provide novel insights into immunogenic epitopes of spike proteins, which can further be evaluated as potential vaccine candidates against COVID-19. Prioritized epitopes were then modeled using linkers and adjuvants, and respective 3D models were constructed to evaluate their physiochemical properties and their possible interactions with ACE2, HLA Superfamily alleles, TLR2, and TLR4.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Sequência de Aminoácidos , Infecções por Coronavirus/virologia , Epitopos de Linfócito B/química , Epitopos de Linfócito T/química , Antígenos HLA/química , Antígenos HLA/imunologia , Humanos , Modelos Químicos , Simulação de Acoplamento Molecular , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/virologia , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Glicoproteína da Espícula de Coronavírus/imunologia , Receptor 2 Toll-Like/química , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/química , Receptor 4 Toll-Like/imunologia , Vacinas Virais/química
3.
BMC Bioinformatics ; 21(1): 295, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640979

RESUMO

BACKGROUND: The human leukocyte antigen (HLA) gene family plays a key role in the immune response and thus is crucial in many biomedical and clinical settings. Utilizing Sanger sequencing, the golden standard technology for HLA typing enables accurate identification of HLA alleles in high-resolution. However, only the commercial software, such as uTYPE, SBT-Assign, and SBTEngine, and very few open-source tools could be applied to perform HLA typing based on Sanger sequencing. RESULTS: We developed a user-friendly, cross-platform and open-source desktop application, known as SOAPTyping, for Sanger-based typing in HLA class I and II alleles. SOAPTyping can produce accurate results with a comprehensible protocol and featured functions. Moreover, SOAPTyping supports a more advanced group-specific sequencing primers (GSSP) module to solve the ambiguous typing results. We used SOAPTyping to analyze 36 samples with known HLA typing from the University of California Los Angeles (UCLA) International HLA DNA Exchange platform and 100 anonymous clinical samples, and the HLA typing results from SOAPTyping are identical to the golden results and 5.5 times faster than commercial software uTYPE, which shows the usability of SOAPTyping. CONCLUSIONS: We introduce the SOAPTyping as the first open-source and cross-platform HLA typing software with the capability of producing high-resolution HLA typing predictions from Sanger sequence data.


Assuntos
Antígenos HLA/genética , Teste de Histocompatibilidade/métodos , Análise de Sequência de DNA , Software , Alelos , Primers do DNA , Antígenos de Histocompatibilidade Classe I , Antígenos de Histocompatibilidade Classe II , Humanos
4.
PLoS Negl Trop Dis ; 14(7): e0008436, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32639997

RESUMO

Nodding syndrome (NS) is a devastating and enigmatic childhood epilepsy. NS is accompanied by multiple neurological impairments and neuroinflammation, and associated with the parasite Onchocerca volvulus (Ov) and other environmental factors. Moreover, NS seems to be an 'Autoimmune Epilepsy' since: 1. ~50% of NS patients have neurotoxic cross-reactive Ov/Leimodin-I autoimmune antibodies. 2. Our recently published findings: Most (~86%) of NS patients have glutamate-receptor AMPA-GluR3B peptide autoimmune antibodies that bind, induce Reactive Oxygen Species, and kill both neural cells and T cells. Furthermore, NS patient's IgG induce seizures, brain multiple damage alike occurring in brains of NS patients, and elevation of T cells and activated microglia and astrocytes, in brains of normal mice. Human Leukocyte antigen (HLA) class I and II molecules are critical for initiating effective beneficial immunity against foreign microorganisms and contributing to proper brain function, but also predispose to detrimental autoimmunity against self-peptides. We analyzed seven HLA loci, either by next-generation-sequencing or Sequence-Specific-Oligonucleotide-Probe, in 48 NS patients and 51 healthy controls from South Sudan. We discovered that NS associates significantly with both protective HLA haplotype: HLA-B*42:01, C*17:01, DRB1*03:02, DQB1*04:02 and DQA1*04:01, and susceptible motif: Ala24, Glu63 and Phe67, in the HLA-B peptide-binding groove. These amino acids create a hydrophobic and sterically closed peptide-binding HLA pocket, favoring proline residue. Our findings suggest that immunogenetic fingerprints in HLA peptide-binding grooves tentatively associate with protection or susceptibility to NS. Accordingly, different HLA molecules may explain why under similar environmental factors, only some children, within the same families, tribes and districts, develop NS, while others do not.


Assuntos
Antígenos HLA/química , Antígenos HLA/imunologia , Síndrome do Cabeceio/imunologia , Adolescente , Adulto , Motivos de Aminoácidos , Autoanticorpos/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Suscetibilidade a Doenças , Feminino , Antígenos HLA/genética , Humanos , Masculino , Síndrome do Cabeceio/genética , Síndrome do Cabeceio/prevenção & controle , Receptores de AMPA/genética , Receptores de AMPA/imunologia , Sudão do Sul , Adulto Jovem
5.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32675312

RESUMO

BACKGROUND: Pandemic COVID-19 by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) infection is facilitated by the ACE2 receptor and protease TMPRSS2. Modestly sized case series have described clinical factors associated with COVID-19, while ACE2 and TMPRSS2 expression analyses have been described in some cell types. Patients with cancer may have worse outcomes to COVID-19. METHODS: We performed an integrated study of ACE2 and TMPRSS2 gene expression across and within organ systems, by normal versus tumor, across several existing databases (The Cancer Genome Atlas, Census of Immune Single Cell Expression Atlas, The Human Cell Landscape, and more). We correlated gene expression with clinical factors (including but not limited to age, gender, race, body mass index, and smoking history), HLA genotype, immune gene expression patterns, cell subsets, and single-cell sequencing as well as commensal microbiome. RESULTS: Matched normal tissues generally display higher ACE2 and TMPRSS2 expression compared with cancer, with normal and tumor from digestive organs expressing the highest levels. No clinical factors were consistently identified to be significantly associated with gene expression levels though outlier organ systems were observed for some factors. Similarly, no HLA genotypes were consistently associated with gene expression levels. Strong correlations were observed between ACE2 expression levels and multiple immune gene signatures including interferon-stimulated genes and the T cell-inflamed phenotype as well as inverse associations with angiogenesis and transforming growth factor-ß signatures. ACE2 positively correlated with macrophage subsets across tumor types. TMPRSS2 was less associated with immune gene expression but was strongly associated with epithelial cell abundance. Single-cell sequencing analysis across nine independent studies demonstrated little to no ACE2 or TMPRSS2 expression in lymphocytes or macrophages. ACE2 and TMPRSS2 gene expression associated with commensal microbiota in matched normal tissues particularly from colorectal cancers, with distinct bacterial populations showing strong associations. CONCLUSIONS: We performed a large-scale integration of ACE2 and TMPRSS2 gene expression across clinical, genetic, and microbiome domains. We identify novel associations with the microbiota and confirm host immunity associations with gene expression. We suggest caution in interpretation regarding genetic associations with ACE2 expression suggested from smaller case series.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Neoplasias/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Serina Endopeptidases/metabolismo , Idoso , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Conjuntos de Dados como Assunto , Feminino , Microbioma Gastrointestinal/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Antígenos HLA/sangue , Antígenos HLA/imunologia , Humanos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/microbiologia , Neoplasias/patologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , RNA-Seq
6.
Exp Clin Transplant ; 18(3): 275-283, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-594579

RESUMO

OBJECTIVES: COVID-19 is a great threat to the modern world and significant threat to immunocompromised patients, including patients with chronic renal failure. We evaluated COVID-19 incidence among our hemodialysis patients and investigated the most probable immune mechanisms against COVID-19. MATERIALS AND METHODS: Baskent University has 21 dialysis centers across Turkey, with 2420 patients on hemodialysis and 30 on peritoneal dialysis. Among these, we retrospectively evaluated 602 patients (257 female/345 male) with chronic renal failure receiving hemodialysis as renal replacement therapy; 7 patients (1.1%) were infected with SARS-CoV-2. We retrospectively collected patient demographic characteristics, clinical data, and immunological factors affecting the clinical course of the disease. We divided patients into groups and included 2 control groups (individuals with normal renal functions): group I included COVID-19-positive patients with normal renal function, group II included COVID-19-positive hemodialysis patients, group III included COVID-19-negative hemodialysis patients, and group IV included COVID-19-negative patients with normal renal function. Lymphocyte subsets in peripheral blood and typing of human leukocyte antigens were analyzed in all groups, with killer cell immunoglobulin like receptor genes analyzed only in COVID-19-positive patients and healthy controls. RESULTS: No deaths occurred among the 7 COVID-19-positive hemodialysis patients. Group I patients were significantly older than patients in groups II and III (P = .039, P = .030, respectively) but not significantly different from group IV (P = .060). Absolute counts of natural killer cells in healthy controls were higherthan in other groups (but not significantly). ActivatedT cells were significantly increased in both COVID-19-positive groups versus COVID-19-negative groups. Groups showed significant differences in C and DQ loci with respect to distribution of alleles in both HLA classes. CONCLUSIONS: Although immunocompromised patients are at greater risk for COVID-19, we found lower COVID-19 incidence in our hemodialysis patients, which should be further investigated in in vitro and molecular studies.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Hospedeiro Imunocomprometido , Falência Renal Crônica/terapia , Infecções Oportunistas/epidemiologia , Pneumonia Viral/epidemiologia , Diálise Renal/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Antígenos HLA/imunologia , Interações Hospedeiro-Patógeno , Humanos , Incidência , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/imunologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Linfócitos T/imunologia , Resultado do Tratamento , Turquia/epidemiologia , Adulto Jovem
7.
Immunobiology ; 225(3): 151955, 2020 05.
Artigo em Inglês | MEDLINE | ID: covidwho-309013

RESUMO

SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus. So far, the pandemic has caused the death of hundreds of thousands of people upon infection and spreading. To date, no effective vaccine is available which can combat the infection caused by this virus. Therefore, this study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation, three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against the SARS-CoV-2. Thereafter, the molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. This study should contribute to uphold the present efforts of the researches to secure a definitive preventative measure against this lethal disease.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Proteínas Virais/química , Vacinas Virais/biossíntese , Sequência de Aminoácidos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Biologia Computacional/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Progressão da Doença , Epitopos/química , Epitopos/imunologia , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunogenicidade da Vacina , Simulação de Acoplamento Molecular , Plasmídeos/química , Plasmídeos/imunologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Conformação Proteica , Genética Reversa/métodos , Alinhamento de Sequência , Vacinas de Subunidades , Proteínas Virais/genética , Proteínas Virais/imunologia
8.
HLA ; 96(3): 277-298, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32475052

RESUMO

We report detailed peptide-binding affinities between 438 HLA Class I and Class II proteins and complete proteomes of seven pandemic human viruses, including coronaviruses, influenza viruses and HIV-1. We contrast these affinities with HLA allele frequencies across hundreds of human populations worldwide. Statistical modelling shows that peptide-binding affinities classified into four distinct categories depend on the HLA locus but that the type of virus is only a weak predictor, except in the case of HIV-1. Among the strong HLA binders (IC50 ≤ 50), we uncovered 16 alleles (the top ones being A*02:02, B*15:03 and DRB1*01:02) binding more than 1% of peptides derived from all viruses, 9 (top ones including HLA-A*68:01, B*15:25, C*03:02 and DRB1*07:01) binding all viruses except HIV-1, and 15 (top ones A*02:01 and C*14:02) only binding coronaviruses. The frequencies of strongest and weakest HLA peptide binders differ significantly among populations from different geographic regions. In particular, Indigenous peoples of America show both higher frequencies of strongest and lower frequencies of weakest HLA binders. As many HLA proteins are found to be strong binders of peptides derived from distinct viral families, and are hence promiscuous (or generalist), we discuss this result in relation to possible signatures of natural selection on HLA promiscuous alleles due to past pathogenic infections. Our findings are highly relevant for both evolutionary genetics and the development of vaccine therapies. However they should not lead to forget that individual resistance and vulnerability to diseases go beyond the sole HLA allelic affinity and depend on multiple, complex and often unknown biological, environmental and other variables.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por HIV/epidemiologia , Antígenos HLA/química , Influenza Humana/epidemiologia , Pandemias , Peptídeos/química , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Proteínas Virais/química , África/epidemiologia , América/epidemiologia , Sequência de Aminoácidos , Ásia/epidemiologia , Austrália/epidemiologia , Betacoronavirus/genética , Betacoronavirus/imunologia , Biologia Computacional , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Europa (Continente)/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/imunologia , Antígenos HLA/classificação , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/imunologia , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Influenza Humana/virologia , Cinética , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Peptídeos/genética , Peptídeos/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Ligação Proteica , Vírus da SARS/genética , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Proteínas Virais/genética , Proteínas Virais/imunologia
10.
Exp Clin Transplant ; 18(3): 275-283, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32519618

RESUMO

OBJECTIVES: COVID-19 is a great threat to the modern world and significant threat to immunocompromised patients, including patients with chronic renal failure. We evaluated COVID-19 incidence among our hemodialysis patients and investigated the most probable immune mechanisms against COVID-19. MATERIALS AND METHODS: Baskent University has 21 dialysis centers across Turkey, with 2420 patients on hemodialysis and 30 on peritoneal dialysis. Among these, we retrospectively evaluated 602 patients (257 female/345 male) with chronic renal failure receiving hemodialysis as renal replacement therapy; 7 patients (1.1%) were infected with SARS-CoV-2. We retrospectively collected patient demographic characteristics, clinical data, and immunological factors affecting the clinical course of the disease. We divided patients into groups and included 2 control groups (individuals with normal renal functions): group I included COVID-19-positive patients with normal renal function, group II included COVID-19-positive hemodialysis patients, group III included COVID-19-negative hemodialysis patients, and group IV included COVID-19-negative patients with normal renal function. Lymphocyte subsets in peripheral blood and typing of human leukocyte antigens were analyzed in all groups, with killer cell immunoglobulin like receptor genes analyzed only in COVID-19-positive patients and healthy controls. RESULTS: No deaths occurred among the 7 COVID-19-positive hemodialysis patients. Group I patients were significantly older than patients in groups II and III (P = .039, P = .030, respectively) but not significantly different from group IV (P = .060). Absolute counts of natural killer cells in healthy controls were higherthan in other groups (but not significantly). ActivatedT cells were significantly increased in both COVID-19-positive groups versus COVID-19-negative groups. Groups showed significant differences in C and DQ loci with respect to distribution of alleles in both HLA classes. CONCLUSIONS: Although immunocompromised patients are at greater risk for COVID-19, we found lower COVID-19 incidence in our hemodialysis patients, which should be further investigated in in vitro and molecular studies.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Hospedeiro Imunocomprometido , Falência Renal Crônica/terapia , Infecções Oportunistas/epidemiologia , Pneumonia Viral/epidemiologia , Diálise Renal/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Antígenos HLA/imunologia , Interações Hospedeiro-Patógeno , Humanos , Incidência , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/imunologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Linfócitos T/imunologia , Resultado do Tratamento , Turquia/epidemiologia , Adulto Jovem
11.
Immunobiology ; 225(3): 151955, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32517882

RESUMO

SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus. So far, the pandemic has caused the death of hundreds of thousands of people upon infection and spreading. To date, no effective vaccine is available which can combat the infection caused by this virus. Therefore, this study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation, three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against the SARS-CoV-2. Thereafter, the molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. This study should contribute to uphold the present efforts of the researches to secure a definitive preventative measure against this lethal disease.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Proteínas Virais/química , Vacinas Virais/biossíntese , Sequência de Aminoácidos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Biologia Computacional/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Progressão da Doença , Epitopos/química , Epitopos/imunologia , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunogenicidade da Vacina , Simulação de Acoplamento Molecular , Plasmídeos/química , Plasmídeos/imunologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Conformação Proteica , Genética Reversa/métodos , Alinhamento de Sequência , Vacinas de Subunidades , Proteínas Virais/genética , Proteínas Virais/imunologia
13.
Biomed Res Int ; 2020: 2683286, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-400795

RESUMO

Background: A new endemic disease has spread across Wuhan City, China, in December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a "public-health emergency of international concern" due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus, the objective of this study is to design a multiepitope peptide vaccine against COVID-19 using an immunoinformatics approach. Method: Several techniques facilitating the combination of the immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the envelope protein of 2019-nCoV as a target. Results: Extensive mutations, insertion, and deletion were discovered with comparative sequencing in the COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. Conclusion: The T-cell epitope-based peptide vaccine was designed for COVID-19 using the envelope protein as an immunogenic target. Nevertheless, the proposed vaccine rapidly needs to be validated clinically in order to ensure its safety and immunogenic profile to help stop this epidemic before it leads to devastating global outbreaks.


Assuntos
Betacoronavirus/imunologia , Biologia Computacional/métodos , Infecções por Coronavirus/imunologia , Epitopos/imunologia , Pneumonia Viral/imunologia , Vacinas de Subunidades/imunologia , Proteínas Virais/imunologia , Vacinas Virais/imunologia , Sequência de Aminoácidos , Infecções por Coronavirus/prevenção & controle , Epitopos/química , Epitopos de Linfócito T/imunologia , Evolução Molecular , Antígenos HLA/imunologia , Humanos , Modelos Moleculares , Pandemias , Software , Proteínas Virais/química
14.
Eur Rev Med Pharmacol Sci ; 24(8): 4607-4615, 2020 04.
Artigo em Inglês | MEDLINE | ID: covidwho-205205

RESUMO

COVID-19 pandemic can cause irreparable damage to the involved society. This study aimed to provide a summary of the up-to-dated clinical display, diagnostics, molecular and genetic implications for COVID-19 infected patients. In this review, 73 research articles published before 25 March 2020 were analyzed to better understand the clinical characteristics of patients and to introduce the available serological, hematology and molecular diagnostic methods. Apart from articles extracted from PubMed and Google Scholar, WHO (https://www.who.int/), NHC (National Health Commission of the People's Republic of China (http://www.nhc.gov.cn/), NICE (National Institute for Health and Clinical Excellence, https://www.nice.org.uk/), CDC (Centers for Disease Control and Prevention, https://www.cdc.gov/), and National Administration of Traditional Chinese Medicine (http://www.satcm.gov.cn/) were also accessed to search for eligible studies. Papers published between January 1, 2020, and 25 March 2020 were searched in English and the terms "2019-nCoV, Covid-19, Clinical Characteristics OR manifestation, method of detection, COVID-19 Genome and molecular test" were used. As the pandemic continues to evolve, there have been reports about the possibility of asymptomatic transmission of this newly emerged pneumonia virus. We highlighted the role of HLA haplotype in virus infection as HLA typing will provide susceptibility information for personalized prevention, diagnosis, and treatment in future studies. All the data in this article will assist researchers and clinicians to develop their clinical views regarding infected patients and to emphasize the origin of SARS-CoV-2 for diagnostics.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Antígenos HLA/genética , Pneumonia Viral/diagnóstico , Autopsia , Doenças Cardiovasculares/etiologia , Infecções por Coronavirus/complicações , Genoma Viral , Haplótipos , Humanos , Nefropatias/etiologia , Hepatopatias/etiologia , Pandemias , Pneumonia Viral/complicações , RNA Viral/isolamento & purificação , Manejo de Espécimes
15.
Hum Cell ; 33(3): 537-544, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32449112

RESUMO

Previous studies have shown that some specific long non-coding RNAs are dysregulated in vascular walls and abnormally expressed in vascular disease. LncRNA HLA complex group 18 (HCG18) is a member of the HLA complex group, which has been rarely investigated in human diseases. In this study, we aimed to investigate the role of HCG in vascular smooth muscle cells. HCG18 was over-expressed by adenovirus transfection and knocked down in vascular smooth muscle cells by shRNA. Cell proliferation was detected by CCK-8 assays. Flow cytometry was employed to test the impacts of HCG18 on vascular smooth muscle apoptotic cells. The expression of associated genes in protein and mRNA levels was detected by western blotting, immunofluorescence and qRT-PCR. The interactions between HCG18 and fused in sarcoma (FUS) were confirmed by RNA EMSA and RIP assays. The expression of serum HCG18 was decreased in hypertensive patients and PDGF-BB-treated vascular smooth muscle cells. HCG18 inhibited proliferation and induced apoptotic cells in vascular smooth muscle cells. In addition, we also found that HCG18 can inhibit vascular smooth muscle cell phenotypic switching from a contractile to a secretory phenotype. Finally, our results showed that HCG18 enhanced apoptotic cells by directly binding with FUS. Our findings reveal that HCG18 is involved in the regulation of proliferation, apoptosis and the expression levels of markers of the contractile and synthetic phenotype.


Assuntos
Proliferação de Células/genética , Antígenos HLA/fisiologia , Músculo Liso Vascular/citologia , Fenótipo , RNA Longo não Codificante/fisiologia , Apoptose/genética , Células Cultivadas , Expressão Gênica/genética , Antígenos HLA/genética , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
16.
HLA ; 96(2): 194-196, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32424945

RESUMO

COVID-19 is a respiratory disease caused by a novel coronavirus and is currently a global pandemic. HLA variation is associated with COVID-19 because HLA plays a pivotal role in the immune response to pathogens. Here, 82 individuals with COVID-19 were genotyped for HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 loci using next-generation sequencing (NGS). Frequencies of the HLA-C*07:29, C*08:01G, B*15:27, B*40:06, DRB1*04:06, and DPB1*36:01 alleles were higher, while the frequencies of the DRB1*12:02 and DPB1*04:01 alleles were lower in COVID-19 patients than in the control population, with uncorrected statistical significance. Only HLA-C*07:29 and B*15:27 were significant when the corrected P-value was considered. These data suggested that some HLA alleles may be associated with the occurrence of COVID-19.


Assuntos
Infecções por Coronavirus/genética , Antígenos HLA/genética , Pneumonia Viral/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Betacoronavirus , China/epidemiologia , Infecções por Coronavirus/imunologia , Frequência do Gene , Genótipo , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Sistema Imunitário , Modelos Estatísticos , Pandemias , Pneumonia Viral/imunologia , Polimorfismo Genético
17.
Biomed Res Int ; 2020: 2683286, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32461973

RESUMO

Background: A new endemic disease has spread across Wuhan City, China, in December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a "public-health emergency of international concern" due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus, the objective of this study is to design a multiepitope peptide vaccine against COVID-19 using an immunoinformatics approach. Method: Several techniques facilitating the combination of the immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the envelope protein of 2019-nCoV as a target. Results: Extensive mutations, insertion, and deletion were discovered with comparative sequencing in the COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. Conclusion: The T-cell epitope-based peptide vaccine was designed for COVID-19 using the envelope protein as an immunogenic target. Nevertheless, the proposed vaccine rapidly needs to be validated clinically in order to ensure its safety and immunogenic profile to help stop this epidemic before it leads to devastating global outbreaks.


Assuntos
Betacoronavirus/imunologia , Biologia Computacional/métodos , Infecções por Coronavirus/imunologia , Epitopos/imunologia , Pneumonia Viral/imunologia , Vacinas de Subunidades/imunologia , Proteínas Virais/imunologia , Vacinas Virais/imunologia , Sequência de Aminoácidos , Infecções por Coronavirus/prevenção & controle , Epitopos/química , Epitopos de Linfócito T/imunologia , Evolução Molecular , Antígenos HLA/imunologia , Humanos , Modelos Moleculares , Pandemias , Software , Proteínas Virais/química
18.
Eur Rev Med Pharmacol Sci ; 24(8): 4607-4615, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32374001

RESUMO

COVID-19 pandemic can cause irreparable damage to the involved society. This study aimed to provide a summary of the up-to-dated clinical display, diagnostics, molecular and genetic implications for COVID-19 infected patients. In this review, 73 research articles published before 25 March 2020 were analyzed to better understand the clinical characteristics of patients and to introduce the available serological, hematology and molecular diagnostic methods. Apart from articles extracted from PubMed and Google Scholar, WHO (https://www.who.int/), NHC (National Health Commission of the People's Republic of China (http://www.nhc.gov.cn/), NICE (National Institute for Health and Clinical Excellence, https://www.nice.org.uk/), CDC (Centers for Disease Control and Prevention, https://www.cdc.gov/), and National Administration of Traditional Chinese Medicine (http://www.satcm.gov.cn/) were also accessed to search for eligible studies. Papers published between January 1, 2020, and 25 March 2020 were searched in English and the terms "2019-nCoV, Covid-19, Clinical Characteristics OR manifestation, method of detection, COVID-19 Genome and molecular test" were used. As the pandemic continues to evolve, there have been reports about the possibility of asymptomatic transmission of this newly emerged pneumonia virus. We highlighted the role of HLA haplotype in virus infection as HLA typing will provide susceptibility information for personalized prevention, diagnosis, and treatment in future studies. All the data in this article will assist researchers and clinicians to develop their clinical views regarding infected patients and to emphasize the origin of SARS-CoV-2 for diagnostics.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Antígenos HLA/genética , Pneumonia Viral/diagnóstico , Autopsia , Doenças Cardiovasculares/etiologia , Infecções por Coronavirus/complicações , Genoma Viral , Haplótipos , Humanos , Nefropatias/etiologia , Hepatopatias/etiologia , Pandemias , Pneumonia Viral/complicações , RNA Viral/isolamento & purificação , Manejo de Espécimes
19.
Transplant Proc ; 52(3): 754-758, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32248911

RESUMO

OBJECTIVE: Successful allogeneic hematopoietic stem cell transplantation (HSCT) relies on human leukocyte antigen (HLA) matching. However, whether HLA-matching between donors and recipients increases recipients' risk of genetic disease remains unclear. METHODS: We investigated whether HLA-matched donor cells used for HSCT have similar microsatellite DNA polymorphisms to HSCT recipients at 19 randomly selected loci including CSF1PO, D12S391, D13S317, D16S539, D18S51, D19S433, D21S11, D2S1338, D3S1358, D5S818, D6S1043, D7S820, D8S1179, FGA, PentaD, PentaE, TH01, TPOX, and VWA. We analyzed allele matching at each short tandem repeat (STR) loci in HLA-matched and mismatched (control) groups using binary outcomes and a quantitative numerical method. RESULTS: The frequencies were similar between the HLA-matched group and the mismatched group for D6S1043. However, the allele matching rate was higher in the HLA-matched group than that in the mismatched group at 14 of the 19 STR loci. Overall, a significant increase in the rate of STR matching was observed in the HLA-matched group compared to the mismatched group (P = .004). CONCLUSION: It would be interesting to know if the HLA matched pairs came more often in question than their mismatched counterparts as candidates for fully HLA-matched unrelated HSCT. The actual risk for HSCT donors developing these diseases needs further evaluation.


Assuntos
Antígenos HLA , Transplante de Células-Tronco Hematopoéticas , Polimorfismo Genético , Doadores de Tecidos , Alelos , Aloenxertos , Frequência do Gene , Genética Populacional , Células-Tronco Hematopoéticas , Humanos , Repetições de Microssatélites , Fatores de Risco
20.
Ann Thorac Surg ; 110(2): 414-423, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32251655

RESUMO

BACKGROUND: Sensitized candidates with unacceptable antigens are a group that demands special attention in organ transplantation. Calculated panel reactive antigen (cPRA) is not used to modify allocation priorities in lung transplantation. The impact of cPRA on waiting list time and mortality is unknown. METHODS: We performed a retrospective review of candidates for lung transplantation listed from May 2005 to 2018. Data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing STAR (Standard Analysis and Research) dataset was paired with additional unacceptable human leukocyte antigen (UA-HLA) data, which were used to calculate the listing cPRA. Candidates were stratified based on the lack of UA-HLAs or cPRA level for candidates with unacceptable antigens reported. Unadjusted competing risks and adjusted subdistribution hazard models were fit. RESULTS: A total of 29,085 candidates met inclusion criteria for analysis. Of these, 23,562 (81%) with no UA-HLAs, 3472 (11.9%) with a cPRA less than 50, and 2051 with a cPRA greater than or equal to 50 (7.1%). On adjusted analysis, a cPRA greater than or equal to 50 was independently associated with increased waitlist mortality at 1 year (hazard ratio, 1.71; 95% confidence interval, 1.55-1.88; P < .001) and decreased rate of transplantation (71.9% vs 69.5% vs 44.4%; P < .001). Furthermore, patients with a cPRA greater than or equal to 50 had a longer waitlist time compared with a cPRA less than 50 and no UA-HLA candidates (mean 293.69 days vs 162.38 days and 143.26 days, respectively; P < .001). However, once transplanted, posttransplant survival among the cohorts was similar. CONCLUSIONS: Further evaluation of organ allocation with consideration of a candidate's cPRA may be warranted in order to optimize equity in access to transplants.


Assuntos
Antígenos HLA/sangue , Transplante de Pulmão/mortalidade , Seleção de Pacientes , Imunologia de Transplantes , Listas de Espera/mortalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Obtenção de Tecidos e Órgãos/métodos
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