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1.
Nat Commun ; 12(1): 2055, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824342

RESUMO

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.


Assuntos
Antivirais/farmacologia , /virologia , Reações Cruzadas/imunologia , Imunoensaio/métodos , Linfócitos T/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Citocinas/metabolismo , Células HEK293 , Pessoal de Saúde , Humanos , Imunoglobulina G/imunologia , Memória Imunológica , Interferon gama/metabolismo , Pandemias , Peptídeos/metabolismo , /efeitos dos fármacos
2.
Nat Commun ; 12(1): 2037, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795692

RESUMO

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.


Assuntos
Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , /imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , /imunologia , Criança , Pré-Escolar , Reações Cruzadas/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Pessoa de Meia-Idade , Receptores de IgG/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto Jovem
3.
Virol J ; 18(1): 54, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33706767

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic remains ongoing around the world, including in areas where dengue is endemic. Dengue and COVID-19, to some extent, have similar clinical and laboratory features, which can lead to misdiagnosis, delayed treatment and patient's isolation. The use of rapid diagnostic tests (RDT) is easy and convenient for fast diagnosis, however there may be issues with cross-reactivity with antibodies for other pathogens. METHODS: We assessed the possibility of cross-reactivity between SARS-CoV-2 and dengue antibodies by: (1) testing five brands of COVID-19 IgG / IgM RDTs on 60 RT-PCR-confirmed dengue samples; (2) testing 95 RT-PCR-confirmed COVID-19 samples on dengue RDT; and (3) testing samples positive for COVID-19 IgG and/or IgM on dengue RDT. RESULTS: We observed a high specificity across all five brands of COVID-19 RDTs, ranging from 98.3 to 100%. Out of the confirmed COVID-19 samples, one patient tested positive for dengue IgM only, another tested positive for dengue IgG only. One patient tested positive for dengue IgG, IgM, and NS1, suggesting a co-infection. In COVID-19 IgG and/or IgM samples, 6.3% of COVID-19 IgG-positive samples also tested positive for dengue IgG, while 21.1% of COVID-19 IgM-positive samples also tested positive for dengue IgG. CONCLUSION: Despite the high specificity of the COVID-19 RDT, we observed cross-reactions and false-positive results between dengue and COVID-19. Dengue and COVID-19 co-infection was also found. Health practitioners in dengue endemic areas should be careful when using antibody RDT for the diagnosis of dengue during the COVID-19 pandemic to avoid misdiagnosis.


Assuntos
Anticorpos Antivirais/imunologia , Reações Cruzadas/imunologia , Vírus da Dengue/imunologia , Dengue/diagnóstico , /imunologia , Adolescente , Adulto , Criança , Diagnóstico Diferencial , Testes Diagnósticos de Rotina , Reações Falso-Positivas , Feminino , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Indonésia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Proteínas não Estruturais Virais/imunologia , Adulto Jovem
5.
Emerg Microbes Infect ; 10(1): 664-676, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33734013

RESUMO

Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63, and -HKU1 widely spread in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive. In this study, we profiled the temporal changes of IgG antibody against spike proteins (S-IgG) of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivities of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between the levels of HCoV-OC43 S-IgG and the disease severity in COVID-19 patients. We found that SARS-CoV-2 S-IgG titres mounted until days 22-28, whereas HCoV-OC43 antibody titres increased until days 15-21 and then plateaued until day 46. However, IgG titres against HCoV-NL63, -229E, and -HKU1 showed no significant increase. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detectable in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titres were significantly higher in patients with severe disease than those in mild patients at days 1-21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation. At days 1-10 PSO, HCoV-OC43 S-IgG titres correlated to disease severity in the age group over 60. Our data indicate that there is a correlation between cross-reactive antibody against HCoV-OC43 spike protein and disease severity in COVID-19 patients.


Assuntos
Anticorpos Antivirais/sangue , Coronavirus Humano OC43/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
6.
Nat Commun ; 12(1): 1203, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619277

RESUMO

Influenza A virus infection in swine impacts the agricultural industry in addition to its zoonotic potential. Here, we utilize epigraph, a computational algorithm, to design a universal swine H3 influenza vaccine. The epigraph hemagglutinin proteins are delivered using an Adenovirus type 5 vector and are compared to a wild type hemagglutinin and the commercial inactivated vaccine, FluSure. In mice, epigraph vaccination leads to significant cross-reactive antibody and T-cell responses against a diverse panel of swH3 isolates. Epigraph vaccination also reduces weight loss and lung viral titers in mice after challenge with three divergent swH3 viruses. Vaccination studies in swine, the target species for this vaccine, show stronger levels of cross-reactive antibodies and T-cell responses after immunization with the epigraph vaccine compared to the wild type and FluSure vaccines. In both murine and swine models, epigraph vaccination shows superior cross-reactive immunity that should be further investigated as a universal swH3 vaccine.


Assuntos
Algoritmos , Reações Cruzadas/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Imunidade , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Animais , Formação de Anticorpos/imunologia , Epitopos/imunologia , Feminino , Humanos , Influenza Humana/sangue , Influenza Humana/imunologia , Influenza Humana/virologia , Pulmão/patologia , Pulmão/virologia , Masculino , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/sangue , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Suínos , Linfócitos T/imunologia , Vacinação , Perda de Peso
7.
Cell Rep ; 34(7): 108737, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33545052

RESUMO

In the ongoing coronavirus disease 2019 (COVID-19) pandemic, there remain unanswered questions regarding the nature and significance of the humoral immune response toward other coronavirus infections. Here, we investigate the cross-reactivity of antibodies raised against the first severe acute respiratory syndrome coronavirus (SARS-CoV) for their reactivity toward SARS-CoV-2. We extensively characterize a selection of 10 antibodies covering all of the SARS-CoV structural proteins: spike, membrane, nucleocapsid, and envelope. Although nearly all of the examined SARS-CoV antibodies display some level of reactivity to SARS-CoV-2, we find only partial cross-neutralization for the spike antibodies. The implications of our work are two-fold. First, we establish a set of antibodies with known reactivity to both SARS-CoV and SARS-CoV-2, which will allow further study of both viruses. Second, we provide empirical evidence of the high propensity for antibody cross-reactivity between distinct strains of human coronaviruses, which is critical information for designing diagnostic and vaccine strategies for COVID-19.


Assuntos
Anticorpos Antivirais/imunologia , Vírus da SARS/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , /imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Células HEK293 , Humanos , Imunidade Humoral/imunologia , Pandemias , Vírus da SARS/genética , Glicoproteína da Espícula de Coronavírus/genética
8.
BMC Med ; 19(1): 19, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33430856

RESUMO

BACKGROUND: Cross-reactivity to SARS-CoV-2 from exposure to endemic human coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and COVID-19 severity. Here we explore the potential role of cross-reactivity induced by eHCoVs on age-specific COVID-19 severity in a mathematical model of eHCoV and SARS-CoV-2 transmission. METHODS: We use an individual-based model, calibrated to prior knowledge of eHCoV dynamics, to fully track individual histories of exposure to eHCoVs. We also model the emergent dynamics of SARS-CoV-2 and the risk of hospitalisation upon infection. RESULTS: We hypothesise that primary exposure with any eHCoV confers temporary cross-protection against severe SARS-CoV-2 infection, while life-long re-exposure to the same eHCoV diminishes cross-protection, and increases the potential for disease severity. We show numerically that our proposed mechanism can explain age patterns of COVID-19 hospitalisation in EU/EEA countries and the UK. We further show that some of the observed variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates under this model. CONCLUSIONS: This study provides a "proof of possibility" for certain biological and epidemiological mechanisms that could potentially drive COVID-19-related variation across age groups. Our findings call for further research on the role of cross-reactivity to eHCoVs and highlight data interpretation challenges arising from health care capacity and SARS-CoV-2 testing.


Assuntos
Infecções por Coronavirus , Proteção Cruzada/imunologia , Reações Cruzadas/imunologia , /imunologia , Fatores Etários , /imunologia , Coronavirus/classificação , Coronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Doenças Endêmicas , Hospitalização/estatística & dados numéricos , Humanos , Imunidade Heteróloga/imunologia , Modelagem Computacional Específica para o Paciente , Índice de Gravidade de Doença
9.
Immun Inflamm Dis ; 9(1): 128-133, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33320447

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged throughout the world. Building knowledge around Covid-19 is crucial to devise facts based approaches to respond efficiently against this pandemic. AIM: We aimed to investigate pre-existing humoral cross-reactive immunity to SARS-CoV-2. METHOD: We have tested the reactivity against SARS-CoV-2 nucleocapsid (N) antigen of sera collected from healthy healthcare volunteers in 2014. We assessed immunoglobulins reactive against SARS-CoV-2 N-antigen using a well-validated serological platform; Elecsys assay. RESULTS: Sera from 32 subjects (out of 135 [23.7%]) were reactive to SARS-CoV-2 N-antigen, suggesting the presence of anti-SARS-CoV-2 N-antigen antibodies. CONCLUSION: Although the clinical relevance of the observed reactivity can only be speculated and needs to be investigated, the implication of this finding for coronavirus disease 2019 seroepidemiological survey and vaccines' clinical trials is critical.


Assuntos
/imunologia , Reações Cruzadas/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Humoral , /imunologia , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Feminino , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos
10.
Methods Mol Biol ; 2236: 9-17, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33237536

RESUMO

While myeloid-derived suppressor cells (MDSCs) in humans and mice have been intensively investigated, there is limited knowledge of these cells in nonhuman primates (NHPs). NHPs serve as critical models for late-stage testing of several biomedical inventions before proceeding with clinical trials and it is therefore important to fully understand their immune compartments and similarities with humans. Here, using antihuman cross-reactive antibodies, we provide flow cytometric analysis protocols for identification of MDSCs in the blood of rhesus macaques, one of the major NHP species as experimental models. Discrepancies and similarities between rhesus and human MDSCs are discussed.


Assuntos
Imunofenotipagem/métodos , Células Supressoras Mieloides/citologia , Animais , Anticorpos/metabolismo , Separação Celular , Reações Cruzadas/imunologia , Análise de Dados , Leucócitos Mononucleares/citologia , Macaca mulatta , Células Supressoras Mieloides/metabolismo , Fenótipo , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Coloração e Rotulagem
11.
Rev. esp. quimioter ; 33(6): 392-398, dic. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-195990

RESUMO

Los coronavirus (CoVs) son un amplio grupo de virus en el que se encuentra el SARS-CoV-2 (familia Coronaviridae, subfamilia Coronavirinae, género Betacoronavirus y subgénero Sarbecovirus). Sus principales proteínas estructurales son la de membrana (M), la de envoltura (E), la nucleocápside (N) y la espicular (S). La respuesta inmune frente a SARS-CoV-2 implica la vertiente celular y humoral, con anticuerpos neutralizantes potencialmente defensivos fundamentalmente dirigidos frente al antígeno S. Aunque los datos de seroprevalencia se asumen muy frecuentemente como marcadores de protección, no necesariamentelo son. En España se estima que al menos cuatro quintas partes de la población deberían estar inmuno-protegidas para asegurar la inmunidad de grupo. Dada la alta tasa de letalidad por COVID-19, la adquisición de esta protección únicamente mediante el contagio natural no es asumible y se debe abogar por otras medidas como puede ser la inmunización masiva. En la actualidad existen varios prototipos de vacunas (que incluyen virus vivos, vectores virológicos, péptidos y proteínas y ácidos nucleicos) en diversas etapas de evaluación clínica. Se prevé que en breve alguna de estas nuevas vacunas se encuentre ya disponible en el mercado. En este texto se revisan aspectos relacionados con estos asuntos


The coronavirus are a wide group of viruses among that the SARS-CoV-2 is included (family Coronaviridae, subfamily Coronavirinae, genus Betacoronavirus and subgenus Sarbecovirus). Its main structural proteins are the membrane (M), the envelope (E), the nucleocapsid (N) and spike (S). The immune response to SARS-CoV-2 involves the cellular and the humoral sides, with neutralizing antibodies fundamentally directed against the S antigen. Although the seroprevalence data are frequently assumed as protection markers, no necessarily they are. In Spain, it is estimated that, to assure the herd immunity, at least four-fifths of the population should be immunoprotected. Due the high fatality rate of COVID-19, the acquisition of the protection only by the natural infection it not assumable and other measures as the mass immunization are required. Currently, there are several vaccine prototypes (including life virus, viral vectors, peptides and proteins and nucleic acid) in different phase of clinical evaluation. Foreseeably, some of these news vaccines would be soon commercially available. In this text, aspects related to these issues are reviewed


Assuntos
Humanos , Infecções por Coronavirus/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus/imunologia , Vacinação , Vacinas Virais/imunologia , Pandemias , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Ensaios Clínicos como Assunto/classificação , Reações Cruzadas/imunologia , Imunidade Coletiva/imunologia , Imunização , Testes de Neutralização/métodos , Proteínas Estruturais Virais
12.
Allergol. immunopatol ; 48(6): 589-596, nov.-dic. 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-199247

RESUMO

INTRODUCTION AND OBJECTIVES: Wheat and cereal grains have a broad range of cross-reactivity, but the clinical relevance of this cross-reactivity is uncertain. This study aimed to evaluate clinical and in vitro cross-reactivity with barley, oat, and Job's tears among wheat-allergic patients. MATERIALS AND METHODS: Patients aged 5 to 15 years with IgE-mediated wheat allergy were enrolled. Skin prick test (SPT) and specific IgE (sIgE) to wheat, barley, and oat, and SPT to Job's tears were performed. Oral food challenge (OFC) was conducted if the SPT was ≤5 mm in size and there was no history of anaphylaxis to each grain. Profiles of sIgE bound allergens of wheat, barley, and oat, and inhibition ELISA of IgE binding to barley and oat with wheat were performed. RESULTS: Ten patients with a median age of 8 years were enrolled. Nine of those patients had a history of wheat anaphylaxis. The median SPT size and sIgE level to wheat was 7.3 mm and 146.5 kUA/l, respectively. The cross-reactivity rate for barley, oat, and Job's tears was 60.0%, 33.3%, and 20.0%, respectively. Significantly larger SPT size and higher sIgE level were observed in patients with positive cross-reactivity to barley and oat when compared to patients without cross-reactivity. Barley and oat extracts inhibited 59% and 16% of sIgE bound to wheat gliadins and glutenins, respectively. CONCLUSION: The cross-reactivity rate was quite low for oat and Job's tears compared to that of barley; therefore, avoidance of all cereal grains may be unnecessary in patients with severe wheat allergy


No disponible


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Hipersensibilidade a Trigo/imunologia , Grão Comestível/imunologia , Imunoglobulina E/imunologia , Testes Cutâneos/métodos , Ensaio de Imunoadsorção Enzimática , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Análise de Variância , Fatores de Tempo , Coix/imunologia , Hordeum/imunologia , Avena/imunologia , Reações Cruzadas/imunologia
13.
Viruses ; 13(1)2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33374950

RESUMO

Virus-induced inflammation plays a critical role in determining the clinical outcome of an acute respiratory virus infection. We have shown previously that the administration of immunobiotic Lactobacillus plantarum (Lp) directly to the respiratory tract prevents lethal inflammatory responses to subsequent infection with a mouse respiratory virus pathogen. While Lp-mediated protective responses involve non-redundant contributions of both Toll-like receptor 2 (TLR2) and NOD2, the cellular basis of these findings remains unclear. Here, we address the impact of Lp and its capacity to suppress inflammation in virus-infected respiratory epithelial cells in two cell culture models. We found that both MLE-12 cells and polarized mouse tracheal epithelial cells (mTECs) were susceptible to infection with Influenza A and released proinflammatory cytokines, including CCL2, CCL5, CXCL1, and CXCL10, in response to replicating virus. MLE-12 cells express NOD2 (81 ± 6.3%) and TLR2 (19 ± 4%), respond to Lp, and are TLR2-specific, but not NOD2-specific, biochemical agonists. By contrast, we found that mTECs express NOD2 (81 ± 17%) but minimal TLR2 (0.93 ± 0.58%); nonetheless, mTECs respond to Lp and the TLR2 agonist, Pam2CSK4, but not NOD2 agonists or the bifunctional TLR2-NOD2 agonist, CL-429. Although MLE-12 cells and mTECS were both activated by Lp, little to no cytokine suppression was observed in response to Lp followed by virus infection via a protocol that replicated experimental conditions that were effective in vivo. Further study and a more complex approach may be required to reveal critical factors that suppress virus-induced inflammatory responses.


Assuntos
Reações Cruzadas/imunologia , Inflamação/etiologia , Lactobacillus plantarum/fisiologia , Probióticos , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Animais , Linhagem Celular , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/metabolismo , Imunofenotipagem , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Ligantes , Camundongos , Camundongos Knockout , Receptores de Reconhecimento de Padrão/metabolismo , Mucosa Respiratória/microbiologia , Mucosa Respiratória/patologia , Receptor 2 Toll-Like/metabolismo , Viroses/complicações , Viroses/virologia , Perda de Peso
14.
PLoS Negl Trop Dis ; 14(12): e0008998, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33370333

RESUMO

Clonorchiasis caused by Clonorchis sinensis is endemic in East Asia; approximately 15 million people have been infected thus far. To diagnose the infection, serodiagnostic tests with excellent functionality should be performed. First, 607 expressed sequence tags encoding polypeptides with a secretory signal were expressed into recombinant proteins using an in vitro translation system. By protein array-based screening using C. sinensis-infected sera, 18 antigen candidate proteins were selected and assayed for cross-reactivity against Opisthorchis viverrini-infected sera. Of the six antigenic proteins selected, four were synthesized on large scale in vitro and evaluated for antigenicity against the flukes-infected human sera using ELISA. CsAg17 antigen showed the highest sensitivity (77.1%) and specificity (71.2%). The sensitivity and specificity of the bacterially produced CsAg17-28GST fusion antigen was similar to those of CsAg17 antigen. CsAg17 antigen can be used to develop point-of-care serodiagnostic tests for clonorchiasis.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Clonorquíase/diagnóstico , Clonorchis sinensis/imunologia , Animais , Clonorchis sinensis/genética , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática , Peixes/parasitologia , Humanos , Imunoglobulina G/sangue , Opisthorchis/imunologia , Testes Imediatos , Proteogenômica , Alimentos Crus/parasitologia , Sensibilidade e Especificidade , Testes Sorológicos
15.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375120

RESUMO

Shellfish allergy affects 2% of the world's population and persists for life in most patients. The diagnosis of shellfish allergy, in particular shrimp, is challenging due to the similarity of allergenic proteins from other invertebrates. Despite the clinical importance of immunological cross-reactivity among shellfish species and between allergenic invertebrates such as dust mites, the underlying molecular basis is not well understood. Here we mine the complete transcriptome of five frequently consumed shrimp species to identify and compare allergens with all known allergen sources. The transcriptomes were assembled de novo, using Trinity, from raw RNA-Seq data of the whiteleg shrimp (Litopenaeus vannamei), black tiger shrimp (Penaeus monodon), banana shrimp (Fenneropenaeus merguiensis), king shrimp (Melicertus latisulcatus), and endeavour shrimp (Metapenaeus endeavouri). BLAST searching using the two major allergen databases, WHO/IUIS Allergen Nomenclature and AllergenOnline, successfully identified all seven known crustacean allergens. The analyses revealed up to 39 unreported allergens in the different shrimp species, including heat shock protein (HSP), alpha-tubulin, chymotrypsin, cyclophilin, beta-enolase, aldolase A, and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Multiple sequence alignment (Clustal Omega) demonstrated high homology with allergens from other invertebrates including mites and cockroaches. This first transcriptomic analyses of allergens in a major food source provides a valuable resource for investigating shellfish allergens, comparing invertebrate allergens and future development of improved diagnostics for food allergy.


Assuntos
Alérgenos/genética , Proteínas de Artrópodes/genética , Hipersensibilidade Alimentar/genética , Perfilação da Expressão Gênica/métodos , Penaeidae/genética , Transcriptoma/genética , Alérgenos/imunologia , Animais , Proteínas de Artrópodes/classificação , Proteínas de Artrópodes/imunologia , Reações Cruzadas/imunologia , Evolução Molecular , Hipersensibilidade Alimentar/imunologia , Humanos , Penaeidae/classificação , Penaeidae/imunologia , Filogenia , Alimentos Marinhos/análise , Especificidade da Espécie , Tropomiosina/genética , Tropomiosina/imunologia
16.
Front Immunol ; 11: 2130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013898

RESUMO

In the last decades, a number of infectious viruses have emerged from wildlife or re-emerged, generating serious threats to the global health and to the economy worldwide. Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. Vaccination is probably the most effective tool in helping the immune system to activate protective responses against pathogens, reducing morbidity and mortality, as proven by historical records. Under health emergency conditions, new and alternative approaches in vaccine design and development are imperative for a rapid and massive vaccination coverage, to manage a disease outbreak and curtail the epidemic spread. This review gives an update on the current vaccination strategies for some of the emerging/re-emerging viruses, and discusses challenges and hurdles to overcome for developing efficacious vaccines against future pathogens.


Assuntos
Betacoronavirus/imunologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinação , Vacinas Virais/imunologia , Animais , Anticorpos Facilitadores/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Humanos , Imunização Passiva , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades/imunologia
17.
Pediatr Infect Dis J ; 39(11): e366-e367, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33021596

RESUMO

With recent reports showing clinical and laboratory overlap of multisystem inflammatory syndrome in children and Kawasaki disease (KD), we addressed the hypothesis that cross coronavirus humoral immunity leads to a parallel postinfectious phenomenon explaining similar pathologic findings in KD and multisystem inflammatory syndrome in children. We demonstrated no cross-reactivity in children with KD but observed some nonspecific interactions postintravenous immunoglobulin infusion.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunoglobulinas/imunologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Pneumonia Viral/imunologia , Proteínas Virais/imunologia , Criança , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Humanos , Imunidade Humoral , Imunoglobulinas/sangue , Síndrome de Linfonodos Mucocutâneos/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia
18.
Emerg Microbes Infect ; 9(1): 2013-2019, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32867625

RESUMO

COVID-19 is a new respiratory illness caused by SARS-CoV-2, and has constituted a global public health emergency. Cat is susceptible to SARS-CoV-2. However, the prevalence of SARS-CoV-2 in cats remains largely unknown. Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. Fifteen sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among them, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). In addition, we continuously monitored serum antibody dynamics of two positive cats every 10 days over 130 days. Their serum antibodies reached the peak at 10 days after first sampling, and declined to the limit of detection within 110 days. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/veterinária , Pandemias/veterinária , Pneumonia Viral/veterinária , Animais , Gatos , China , Infecções por Coronavirus/epidemiologia , Coronavirus Felino/imunologia , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina G/sangue , Proteínas do Nucleocapsídeo/imunologia , Fosfoproteínas , Pneumonia Viral/epidemiologia , Glicoproteína da Espícula de Coronavírus/imunologia
20.
PLoS Negl Trop Dis ; 14(9): e0008676, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32956362

RESUMO

Dengue virus (DENV)-associated disease is a growing threat to public health across the globe. Co-circulating as four different serotypes, DENV poses a unique challenge for vaccine design as immunity to one serotype predisposes a person to severe and potentially lethal disease upon infection from other serotypes. Recent experimental studies suggest that an effective vaccine against DENV should elicit a strong T cell response against all serotypes, which could be achieved by directing T cell responses toward cross-serotypically conserved epitopes while avoiding serotype-specific ones. Here, we used experimentally-determined DENV T cell epitopes and patient-derived DENV sequences to assess the cross-serotypic variability of the epitopes. We reveal a distinct near-binary pattern of epitope conservation across serotypes for a large number of DENV epitopes. Based on the conservation profile, we identify a set of 55 epitopes that are highly conserved in at least 3 serotypes. Most of the highly conserved epitopes lie in functionally important regions of DENV non-structural proteins. By considering the global distribution of human leukocyte antigen (HLA) alleles associated with these DENV epitopes, we identify a potentially robust subset of HLA class I and class II restricted epitopes that can serve as targets for a universal T cell-based vaccine against DENV while covering ~99% of the global population.


Assuntos
Reações Cruzadas/imunologia , Vacinas contra Dengue/imunologia , Epitopos de Linfócito T/imunologia , Linfócitos T/imunologia , Dengue/prevenção & controle , Vacinas contra Dengue/genética , Vírus da Dengue/imunologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Modelos Moleculares , Estrutura Terciária de Proteína , Proteoma , Análise de Sequência de Proteína , Sorogrupo
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