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2.
Nat Commun ; 12(1): 4740, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362897

RESUMO

Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Coronavirus Humano 229E/imunologia , Coronavirus Humano NL63/imunologia , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Resfriado Comum/imunologia , Resfriado Comum/virologia , Proteção Cruzada/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue
3.
Front Immunol ; 12: 627568, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995351

RESUMO

The beta-coronavirus SARS-CoV-2 induces severe disease (COVID-19) mainly in elderly persons with risk factors, whereas the majority of patients experience a mild course of infection. As the circulating common cold coronaviruses OC43 and HKU1 share some homologous sequences with SARS-CoV-2, beta-coronavirus cross-reactive T-cell responses could influence the susceptibility to SARS-CoV-2 infection and the course of COVID-19. To investigate the role of beta-coronavirus cross-reactive T-cells, we analyzed the T-cell response against a 15 amino acid long peptide (SCoV-DP15: DLSPRWYFYYLGTGP) from the SARS-CoV-2 nucleoprotein sequence with a high homology to the corresponding sequence (QLLPRWYFYYLGTGP) in OC43 and HKU1. SCoV-DP15-specific T-cells were detected in 4 out of 23 (17.4%) SARS-CoV-2-seronegative healthy donors. As HIV-1 infection is a potential risk factor for COVID-19, we also studied a cohort of HIV-1-infected patients on antiretroviral therapy. 44 out of these 116 HIV-1-infected patients (37.9%) showed a specific recognition of the SCoV-DP15 peptide or of shorter peptides within SCoV-DP15 by CD4+ T-cells and/or by CD8+ T-cells. We could define several new cross-reactive HLA-I-restricted epitopes in the SARS-CoV-2 nucleoprotein such as SPRWYFYYL (HLA-B*07, HLA-B*35), DLSPRWYFYY (HLA-A*02), LSPRWYFYY (HLA-A*29), WYFYYLGTGP and WYFYYLGT. Epitope specific CD8+ T-cell lines recognized corresponding epitopes within OC43 and HKU1 to a similar degree or even at lower peptide concentrations suggesting that they were induced by infection with OC43 or HKU1. Our results confirm that SARS-CoV-2-seronegative subjects can target SARS-CoV-2 not only by beta-coronavirus cross-reactive CD4+ T-cells but also by cross-reactive CD8+ cytotoxic T-cells (CTL). The delineation of cross-reactive T-cell epitopes contributes to an efficient epitope-specific immunomonitoring of SARS-CoV-2-specific T-cells. Further prospective studies are needed to prove a protective role of cross-reactive T-cells and their restricting HLA alleles for control of SARS-CoV-2 infection. The frequent observation of SARS-CoV-2-reactive T-cells in HIV-1-infected subjects could be a reason that treated HIV-1 infection does not seem to be a strong risk factor for the development of severe COVID-19.


Assuntos
Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , Resfriado Comum/imunologia , Epitopos de Linfócito T/imunologia , Nucleoproteínas/imunologia , SARS-CoV-2/imunologia , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Linfócitos T CD4-Positivos/patologia , COVID-19/genética , COVID-19/patologia , Linhagem Celular , Resfriado Comum/genética , Resfriado Comum/patologia , Reações Cruzadas , Epitopos de Linfócito T/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nucleoproteínas/genética , SARS-CoV-2/genética , Linfócitos T Citotóxicos/patologia
4.
Front Immunol ; 12: 675679, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995420

RESUMO

Background: COVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP. Patients and Methods: Patients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed. Results: CCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex. Conclusions: Common cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.


Assuntos
Anticorpos Antivirais , Betacoronavirus/imunologia , COVID-19/terapia , Resfriado Comum/imunologia , Convalescença , Coronavirus Humano OC43/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/mortalidade , Reações Cruzadas , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade
5.
Nature ; 594(7864): 553-559, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33971664

RESUMO

Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID50) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.


Assuntos
Anticorpos Neutralizantes/imunologia , Betacoronavirus/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Resfriado Comum/prevenção & controle , Reações Cruzadas/imunologia , Pandemias , Vacinas Virais/imunologia , Adjuvantes Imunológicos , Administração Intranasal , Animais , COVID-19/epidemiologia , Vacinas contra COVID-19/imunologia , Resfriado Comum/imunologia , Resfriado Comum/virologia , Modelos Animais de Doenças , Feminino , Humanos , Macaca/imunologia , Masculino , Modelos Moleculares , Nanopartículas/química , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Traqueia , Vacinação
6.
J Med Virol ; 93(7): 4544-4548, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33724483

RESUMO

Few studies exist on the clinical manifestation of coronavirus disease 2019 (COVID-19) in patients who previously had a common cold due to an endemic coronavirus (eCoV). In a retrospective scan of the data obtained in our microbiology laboratory, 64 patients who were diagnosed with an eCoV infection between 2016 and 2020 were identified. National COVID-19 surveillance data showed that four (6.2%) of 64 patients were infected with severe acute respiratory syndrome coronavirus 2 by the end of 2020, while, simultaneously, the COVID-19 prevalence in the city of Malatya ranged from 7.8% (polymerase chain reaction-based diagnosis) to 9.2% (total diagnosis). The differences were found statistically significant (6.2% vs. 7.8%, p < .01; 6.2% vs. 9.2%, p < .001). Patient interviews and evaluation of medical records revealed that these four patients did not manifest any severe COVID-19 symptoms despite their substantial comorbidities, and they did not require hospitalization. Consequently, despite a low number of samples, we determined a lower frequency of COVID-19 among the patients who had a prior eCoV infection, and the results of this study support the previous findings that people with a prior eCoV infection develop a milder case of COVID-19. Our results may provide some insights for future studies aiming at vaccine development, but detailed investigations are still required.


Assuntos
COVID-19/imunologia , COVID-19/patologia , Resfriado Comum/imunologia , Resfriado Comum/patologia , Adulto , COVID-19/diagnóstico , Resfriado Comum/diagnóstico , Comorbidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Turquia
7.
JCI Insight ; 6(4)2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33497357

RESUMO

Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these "common cold" viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage immunoprecipitation sequencing. Seroprevalence of antibodies against endemic HCoVs ranged between approximately 4% and 27% depending on the species and cohort. We identified at least 136 novel linear B cell epitopes. Antibody repertoires against endemic HCoVs were qualitatively different between children and adults in that anti-HCoV IgG specificities more frequently found among children targeted functionally important and structurally conserved regions of the spike, nucleocapsid, and matrix proteins. Moreover, antibody specificities targeting the highly conserved fusion peptide region and S2' cleavage site of the spike protein were broadly cross-reactive with peptides of epidemic human and nonhuman coronaviruses. In contrast, an acidic tandem repeat in the N-terminal region of the Nsp3 subdomain of the HCoV-HKU1 polyprotein was the predominant target of antibody responses in adult donors. Our findings shed light on the dominant species-specific and pan-CoV target sites of human antibody responses to coronavirus infection, thereby providing important insights for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.


Assuntos
Anticorpos Antivirais/isolamento & purificação , Resfriado Comum/virologia , Infecções por Coronavirus/imunologia , Coronavirus/imunologia , Doenças Endêmicas , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos , Antígenos Virais/sangue , Antígenos Virais/imunologia , Criança , Pré-Escolar , Resfriado Comum/sangue , Resfriado Comum/epidemiologia , Resfriado Comum/imunologia , Coronavirus/isolamento & purificação , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Reações Cruzadas , Epitopos de Linfócito B/sangue , Epitopos de Linfócito B/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Domínios Proteicos/imunologia , Estudos Retrospectivos , Estudos Soroepidemiológicos , Proteínas Virais/imunologia
8.
J Clin Invest ; 131(1)2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33216734

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues to cause morbidity and mortality. Since SARS coronavirus 2 (SARS-CoV-2) was identified as the cause for COVID-19, some have questioned whether exposure to seasonal common cold coronaviruses (CCCs) could provide tangible protection against SARS-CoV-2 infection or disease. In this issue of the JCI, Sagar et al. examined SARS-CoV-2 infections and outcomes of patients who had previously tested positive or negative for CCC infection (CCC+ or CCC-) by a comprehensive respiratory panel using PCR. No differences were seen between groups in terms of susceptibility to SARS-CoV-2 infection. However, hospitalized patients with a documented history of CCC infection had lower rates of intensive care unit (ICU) admissions and higher rates of survival than hospitalized CCC- patients. While these findings are associative and not causative, they highlight evidence suggesting that previous CCC infection may influence the disease course of SARS-CoV-2 infection.


Assuntos
COVID-19 , Resfriado Comum/imunologia , Pandemias , SARS-CoV-2/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , Resfriado Comum/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade
10.
Med Sci Monit ; 26: e929789, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33239605

RESUMO

Recent studies have shown a significant level of T cell immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in convalescent coronavirus disease 2019 (COVID-19) patients and unexposed healthy individuals. Also, SARS-CoV-2-reactive T memory cells occur in unexposed healthy individuals from endemic coronaviruses that cause the 'common cold.' The finding of the expression of adaptive SARS-CoV-2-reactive T memory cells in unexposed healthy individuals may be due to multiple cross-reactive viral protein targets following previous exposure to endemic human coronavirus infections. The opinion of the authors is that determination of protein sequence homologies across seemingly disparate viral protein libraries may provide epitope-matching data that link SARS-CoV-2-reactive T memory cell signatures to prior administration of cross-reacting vaccines to common viral pathogens. Exposure to SARS-CoV-2 initiates diverse cellular immune responses, including the associated 'cytokine storm'. Therefore, it is possible that the intact virus possesses a required degree of conformational matching, or stereoselectivity, to effectively target its receptor on multiple cell types. Therefore, conformational matching may be viewed as an evolving mechanism of viral infection and viral replication by an evolutionary modification of the angiotensin-converting enzyme 2 (ACE2) receptor required for SARS-CoV-2 binding and host cell entry. The authors propose that convalescent memory T cell immunity in individuals with mild or asymptomatic SARS-CoV-2 infection may result from an evolutionarily adapted immune response to coronavirus and the 'common cold'.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Infecções Assintomáticas , COVID-19/imunologia , Resfriado Comum/imunologia , Memória Imunológica/genética , Anticorpos Antivirais , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/virologia , Resfriado Comum/prevenção & controle , Resfriado Comum/virologia , Reações Cruzadas/genética , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Evolução Molecular , Humanos , Imunidade Celular/genética , Imunogenicidade da Vacina , Rhinovirus/genética , Rhinovirus/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Homologia de Sequência , Índice de Gravidade de Doença , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Internalização do Vírus , Replicação Viral/genética , Replicação Viral/imunologia
11.
J Infect ; 81(6): 923-930, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33127456

RESUMO

BACKGROUND: Immunological cross-reactivity between common cold coronaviruses (CCC) and SARS-CoV-2 might account for the reduced incidence of COVID-19 in children. Evidence to support speculation includes in vitro evidence for humoral and cellular cross-reactivity with SARS-CoV-2 in specimens obtained before the pandemic started. METHOD: We used retrospective health insurance enrollment records, claims, and laboratory results to assemble a cohort of 869,236 insured individuals who had a PCR test for SARS-CoV-2. We estimated the effects of having clinical encounters for various diagnostic categories in the year preceding the study period on the risk of a positive test result. FINDINGS: After adjusting for age, gender and care seeking behavior, we identified that individuals with diagnoses for common cold symptoms, including acute sinusitis, bronchitis, or pharyngitis in the preceding year had a lower risk of testing positive for SARS-CoV-2 (OR=0.76, 95%CI=0.75, 0.77). No reduction in the odds of a positive test for SARS-CoV-2 was seen in individuals under 18 years. The reduction in odds in adults remained stable for four years but was strongest in those with recent common cold symptoms. INTERPRETATION: While this study cannot attribute this association to cross-immunity resulting from a prior CCC infection, it is one potential explanation. Regardless of the cause, the reduction in the odds of being infected by SARS-CoV-2 among those with a recent diagnosis of common cold symptoms may have a role in shifting future COVD-19 infection patterns from endemic to episodic.


Assuntos
COVID-19/epidemiologia , Resfriado Comum/epidemiologia , Infecções por Coronavirus/epidemiologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Resfriado Comum/imunologia , Coronavirus/imunologia , Infecções por Coronavirus/imunologia , Reações Cruzadas , Feminino , Humanos , Imunidade , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
12.
Proc Natl Acad Sci U S A ; 117(44): 27598-27607, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33060297

RESUMO

Human rhinoviruses (RVs) are positive-strand RNA viruses that cause respiratory tract disease in children and adults. Here we show that the innate immune signaling protein STING is required for efficient replication of members of two distinct RV species, RV-A and RV-C. The host factor activity of STING was identified in a genome-wide RNA interference (RNAi) screen and confirmed in primary human small airway epithelial cells. Replication of RV-A serotypes was strictly dependent on STING, whereas RV-B serotypes were notably less dependent. Subgenomic RV-A and RV-C RNA replicons failed to amplify in the absence of STING, revealing it to be required for a step in RNA replication. STING was expressed on phosphatidylinositol 4-phosphate (PI4P)-enriched membranes and was enriched in RV-A16 compared with RV-B14 replication organelles isolated in isopycnic gradients. The host factor activity of STING was species-specific, as murine STING (mSTING) did not rescue RV-A16 replication in STING-deficient cells. This species specificity mapped primarily to the cytoplasmic, ligand-binding domain of STING. Mouse-adaptive mutations in the RV-A16 2C protein allowed for robust replication in cells expressing mSTING, suggesting a role for 2C in recruiting STING to RV-A replication organelles. Palmitoylation of STING was not required for RV-A16 replication, nor was the C-terminal tail of STING that mediates IRF3 signaling. Despite co-opting STING to promote its replication, interferon signaling in response to STING agonists remained intact in RV-A16 infected cells. These data demonstrate a surprising requirement for a key host mediator of innate immunity to DNA viruses in the life cycle of a small pathogenic RNA virus.


Assuntos
Enterovirus/patogenicidade , Interações Hospedeiro-Patógeno/imunologia , Proteínas de Membrana/metabolismo , Replicação Viral/imunologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Resfriado Comum/imunologia , Resfriado Comum/virologia , Enterovirus/genética , Enterovirus/imunologia , Enterovirus/metabolismo , Células HeLa , Humanos , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Lipoilação , Proteínas de Membrana/agonistas , Mutação , Domínios Proteicos/genética , Transdução de Sinais , Especificidade da Espécie , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
13.
J Clin Invest ; 130(12): 6631-6638, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32966269

RESUMO

BACKGROUNDT cell responses to the common cold coronaviruses have not been well characterized. Preexisting T cell immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported, and a recent study suggested that this immunity was due to cross-recognition of the novel coronavirus by T cells specific for the common cold coronaviruses.METHODSWe used the enzyme-linked immunospot (ELISPOT) assay to characterize the T cell responses against peptide pools derived from the spike protein of 3 common cold coronaviruses (HCoV-229E, HCoV-NL63, and HCoV-OC43) and SARS-CoV-2 in 21 healthy donors (HDs) who were seronegative for SARS-CoV-2 and had no known exposure to the virus. An in vitro expansion culture assay was also used to analyze memory T cell responses.RESULTSWe found responses to the spike protein of the 3 common cold coronaviruses in many of the donors. We then focused on HCoV-NL63 and detected broad T cell responses to the spike protein and identified 22 targeted peptides. Interestingly, only 1 study participant had a significant response to SARS-CoV-2 spike or nucleocapsid protein in the ELISPOT assay. In vitro expansion studies suggested that T cells specific for the HCoV-NL63 spike protein in this individual could also recognize SARS-CoV-2 spike protein peptide pools.CONCLUSIONHDs have circulating T cells specific for the spike proteins of HCoV-NL63, HCoV-229E, and HCoV-OC43. T cell responses to SARS-CoV-2 spike and nucleocapsid proteins were present in only 1 participant and were potentially the result of cross-recognition by T cells specific for the common cold coronaviruses. Further studies are needed to determine whether this cross-recognition influences coronavirus disease 2019 (COVID-19) outcomes.


Assuntos
COVID-19/imunologia , Resfriado Comum/imunologia , Coronavirus Humano 229E/imunologia , Coronavirus Humano NL63/imunologia , Coronavirus Humano OC43/imunologia , Imunidade Celular , SARS-CoV-2/imunologia , Linfócitos T/imunologia , Adulto , Reações Cruzadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Biosci Rep ; 40(9)2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32914848

RESUMO

INTRODUCTION: Asthma is a disease that has been associated with the presence of different genetic and socio-environmental factors. OBJECTIVE: To identify and evaluate the seasonality of respiratory syncytial virus (RSV) and human rhinovirus (RV) in asthmatic children and adolescents in tropical climate, as well as to assess the socioeconomic and environmental factors involved. METHODS: The study was conducted in a referral hospital, where a total of 151 children were recruited with a respiratory infection. The International Study of Asthma and Allergies in Childhood (ISAAC) protocol and a questionnaire were applied, and a skin prick test was performed. The nasal swab was collected to detect RV and RSV through molecular assay. National Meteorological Institute (INMET) database was the source of climatic information. RESULTS: The socio-environmental characterization of asthmatic children showed the family history of allergy, disturbed sleep at night, dry cough, allergic rhinitis, individuals sensitized to at least one mite. We identified RV in 75% of children with asthma and 66.7% of RSV in children with asthma. There was an association between the presence of RV and the dry season whereas the presence of the RSV was associated with the rainy season. Contributing to these results, a negative correlation was observed between the RSV and the wind speed and the maximum temperature (T. Max) and a positive correlation with precipitation. CONCLUSIONS: The results suggest a high prevalence of RV and RSV in asthmatic children and the seasonality of these viruses were present in different climatic periods. This has significant implications for understanding short- and long-term clinical complications in asthmatic patients.


Assuntos
Asma/complicações , Resfriado Comum/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Asma/imunologia , Brasil/epidemiologia , Criança , Pré-Escolar , Resfriado Comum/diagnóstico , Resfriado Comum/imunologia , Resfriado Comum/virologia , Feminino , Humanos , Masculino , Prevalência , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Rhinovirus/imunologia , Rhinovirus/isolamento & purificação , Estações do Ano , Clima Tropical
17.
Sci Rep ; 10(1): 9750, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546721

RESUMO

Rhinoviruses (RVs) are the main cause of the common cold worldwide. To date, more than 160 types of the virus have been recognized, categorized into three major species - A, B, and C. There are currently no approved vaccines available to prevent infection with RVs. To elicit antibodies against conserved regions located on capsid proteins of RV A viruses, mice were sequentially vaccinated with DNA plasmids encoding capsid proteins of different RV A types. After a final boost with whole virus, antibody-expressing hybridomas were generated. After isotyping, 11 monoclonal antibodies (mAbs) expressing an IgG subtype Fc-domain were selected for further expansion and purification. Three mAbs showed cross-reactivity against multiple strains of RV A viruses by ELISA, including strains A1A, A1B, A15, A16 and A49. Other mAbs had strain-specific binding patterns, with the majority of mAbs showing reactivity to RV-A15, the strain used for the final vaccination. We found that the RV-A15-specific mAbs, but not the cross-reactive mAbs, had neutralizing activity against RV-A15. An antibody dependent cellular phagocytosis (ADCP) assay revealed substantial ADCP activity for one of the cross-reactive mAbs. Epitope mapping of the neutralizing mAbs via escape mutant virus generation revealed a shared binding epitope on VP1 of RV-A15 for several neutralizing mAbs. The epitope of the ADCP-active, non-neutralizing mAb was determined by microarray analysis of peptides generated from the VP1 capsid protein. VP1-specific, cross-reactive antibodies, especially those with ADCP activity, could contribute to protection against RV infections.


Assuntos
Anticorpos Monoclonais/imunologia , Resfriado Comum/imunologia , Rhinovirus/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Proteínas do Capsídeo/imunologia , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática , Mapeamento de Epitopos , Humanos , Hibridomas/imunologia , Camundongos , Fagocitose/imunologia , Fagocitose/fisiologia , Rhinovirus/genética , Proteínas Virais/imunologia
19.
Front Immunol ; 11: 596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32328066

RESUMO

Introduction: The responses of cystic fibrosis (CF) airway epithelial cells (AEC) to rhinovirus (RV) infection are likely to contribute to early pathobiology of lung disease with increased neutrophilic inflammation and lower apoptosis reported. Necrosis of AEC resulting in airway inflammation driven by IL-1 signaling is a characteristic finding in CF detectable in airways of young children. Being the most common early-life infection, RV-induced epithelial necrosis may contribute to early neutrophilic inflammation in CF via IL-1 signaling. As little is known about IL-1 and biology of CF lung disease, this study assessed cellular and pro-inflammatory responses of CF and non-CF AEC following RV infection, with the hypothesis that RV infection drives epithelial necrosis and IL-1 driven inflammation. Methods:Primary AEC obtained from children with (n = 6) and without CF (n = 6) were infected with RV (MOI 3) for 24 h and viable, necrotic and apoptotic events quantified via flow cytometry using a seven-step gating strategy (% total events). IL-1α, IL-1ß, IL-1Ra, IL-8, CXCL10, CCL5, IFN-ß, IL-28A, IL-28B, and IL-29 were also measured in cell culture supernatants (pg/mL). Results:RV infection reduced viable events in non-CF AEC (p < 0.05), increased necrotic events in non-CF and CF AEC (p < 0.05) and increased apoptotic events in non-CF AEC (p < 0.05). Infection induced IL-1α and IL-1ß production in both phenotypes (p < 0.05) but only correlated with necrosis (IL-1α: r = 0.80; IL-1ß: r = 0.77; p < 0.0001) in CF AEC. RV infection also increased IL-1Ra in non-CF and CF AEC (p < 0.05), although significantly more in non-CF AEC (p < 0.05). Finally, infection stimulated IL-8 production in non-CF and CF AEC (p < 0.05) and correlated with IL-1α (r = 0.63 & r = 0.74 respectively; p < 0.0001). Conclusions:This study found RV infection drives necrotic cell death in CF AEC. Furthermore, RV induced IL-1 strongly correlated with necrotic cell death in these cells. As IL-1R signaling drives airway neutrophilia and mucin production, these observations suggest RV infection early in life may exacerbate inflammation and mucin accumulation driving early CF lung disease. Since IL-1R can be targeted therapeutically with IL-1Ra, these data suggest a new anti-inflammatory therapeutic approach targeting downstream effects of IL-1R signaling to mitigate viral-induced, muco-inflammatory triggers of early lung disease.


Assuntos
Resfriado Comum/imunologia , Fibrose Cística/virologia , Interleucina-1/imunologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia , Pré-Escolar , Resfriado Comum/complicações , Resfriado Comum/patologia , Fibrose Cística/imunologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/patologia , Inflamação/virologia , Masculino , Necrose/patologia , Necrose/virologia , Rhinovirus
20.
Curr Opin Allergy Clin Immunol ; 20(2): 131-137, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31985546

RESUMO

PURPOSE OF REVIEW: Asthma is the most common chronic disease in pediatric age. Childhood-onset asthma, as opposed to adult-onset asthma, is typically characterized by a personal and often a family history of atopy and related markers of type 2-mediated inflammation. However, the interplay between atopy and asthma development is more complex than a linear dose-response relationship. RECENT FINDINGS: Family and personal history of atopic diseases have been confirmed as major risk factors for asthma occurrence and persistence in children. Early life and multiple sensitizations to aeroallergens significantly increase the risk of asthma development in school age. Early life lower respiratory tract viral infections, especially caused by rhinovirus, also increase the susceptibility to atopic asthma in childhood. Human rhinovirus type C receptor CDHR3 polymorphisms have been shown to affect receptor epithelial expression, activation, and asthma development and exacerbation severity in children. Atopic sensitization and respiratory viral infections can synergistically enhance the susceptibility to asthma through multiple mechanisms, including the IgE-mediated inhibition of innate antiviral responses to rhinovirus. Emerging evidence shows that several nonatopic factors are also involved in the asthma pathogenesis in genetically predisposed individuals, including early life exposure to environmental factors, and lung and gut microbiome composition. SUMMARY: The current review outlines recent data on the complex role of atopy in asthma pathogenesis and persistence, and addresses new research topics such as the role of epigenetics and the lung microbiome.


Assuntos
Alérgenos/imunologia , Asma/imunologia , Resfriado Comum/complicações , Exposição Ambiental/efeitos adversos , Hipersensibilidade Imediata/complicações , Alérgenos/efeitos adversos , Asma/genética , Asma/microbiologia , Caderinas/genética , Caderinas/metabolismo , Criança , Doença Crônica , Resfriado Comum/genética , Resfriado Comum/imunologia , Resfriado Comum/virologia , Relação Dose-Resposta Imunológica , Predisposição Genética para Doença , Humanos , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/microbiologia , Imunidade Inata , Imunoglobulina E/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Pulmão/imunologia , Pulmão/microbiologia , Anamnese , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Microbiota/imunologia , Polimorfismo de Nucleotídeo Único , Mucosa Respiratória/imunologia , Mucosa Respiratória/microbiologia , Rhinovirus/imunologia
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