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1.
Molecules ; 26(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199200

RESUMO

Glycan-targeting antibodies and pseudo-antibodies have been extensively studied for their stoichiometry, avidity, and their interactions with the rapidly modifying glycan shield of influenza A. Broadly neutralizing antiviral agents bind in the same order when they neutralize enveloped viruses regardless of the location of epitopes to the host receptor binding site. Herein, we investigated the binding of cyanovirin-N (CV-N) to surface-expressed glycoproteins such as those of human immunodeficiency virus (HIV) gp120, hemagglutinin (HA), and Ebola (GP)1,2 and compared their binding affinities with the binding response to the trimer-folded gp140 using surface plasmon resonance (SPR). Binding-site knockout variants of an engineered dimeric CV-N molecule (CVN2) revealed a binding affinity that correlated with the number of (high-) affinity binding sites. Binding curves were specific for the interaction with N-linked glycans upon binding with two low-affinity carbohydrate binding sites. This biologically active assembly of a domain-swapped CVN2, or monomeric CV-N, bound to HA with a maximum KD of 2.7 nM. All three envelope spike proteins were recognized at a nanomolar KD, whereas binding to HIV neutralizing 2G12 by targeting HA and Ebola GP1,2 was measured in the µM range and specific for the bivalent binding scheme in SPR. In conclusion, invariant structural protein patterns provide a substrate for affinity maturation in the membrane-anchored HA regions, as well as the glycan shield on the membrane-distal HA top part. They can also induce high-affinity binding in antiviral CV-N to HA at two sites, and CVN2 binding is achieved at low-affinity binding sites.


Assuntos
Proteínas de Bactérias/metabolismo , Ebolavirus/metabolismo , HIV-1/metabolismo , Orthomyxoviridae/metabolismo , Polissacarídeos/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas do Envelope Viral/metabolismo , Proteínas de Bactérias/farmacologia , Sítios de Ligação , Ebolavirus/imunologia , Ebolavirus/isolamento & purificação , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/isolamento & purificação , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/metabolismo , Doença pelo Vírus Ebola/virologia , Humanos , Influenza Humana/imunologia , Influenza Humana/metabolismo , Influenza Humana/virologia , Orthomyxoviridae/imunologia , Orthomyxoviridae/isolamento & purificação , Polissacarídeos/imunologia , Ligação Proteica , Proteínas Recombinantes/isolamento & purificação , Proteínas do Envelope Viral/imunologia
2.
Sci Rep ; 11(1): 14295, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253743

RESUMO

Methylene blue is an FDA (Food and Drug Administration) and EMA (European Medicines Agency) approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. In this study, we first evaluated the virucidal activity of methylene blue against influenza virus H1N1 upon different incubation times and in the presence or absence of light activation, and then against SARS-CoV-2. We further assessed the therapeutic activity of methylene blue by administering it to cells previously infected with SARS-CoV-2. Finally, we examined the effect of co-administration of the drug together with immune serum. Our findings reveal that methylene blue displays virucidal preventive or therapeutic activity against influenza virus H1N1 and SARS-CoV-2 at low micromolar concentrations and in the absence of UV-activation. We also confirm that MB antiviral activity is based on several mechanisms of action as the extent of genomic RNA degradation is higher in presence of light and after long exposure. Our work supports the interest of testing methylene blue in clinical studies to confirm a preventive and/or therapeutic efficacy against both influenza virus H1N1 and SARS-CoV-2 infections.


Assuntos
COVID-19/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Azul de Metileno/farmacologia , Inativação de Vírus/efeitos dos fármacos , Animais , COVID-19/genética , COVID-19/virologia , Chlorocebus aethiops , Humanos , Influenza Humana/genética , Influenza Humana/virologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Raios Ultravioleta/efeitos adversos , Células Vero , Inativação de Vírus/efeitos da radiação , Replicação Viral/efeitos dos fármacos , Replicação Viral/efeitos da radiação
3.
Sci Rep ; 11(1): 14341, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253835

RESUMO

Computational models for large, resurgent epidemics are recognized as a crucial tool for predicting the spread of infectious diseases. It is widely agreed, that such models can be augmented with realistic multiscale population models and by incorporating human mobility patterns. Nevertheless, a large proportion of recent studies, aimed at better understanding global epidemics, like influenza, measles, H1N1, SARS, and COVID-19, underestimate the role of heterogeneous mixing in populations, characterized by strong social structures and geography. Motivated by the reduced tractability of studies employing homogeneous mixing, which make conclusions hard to deduce, we propose a new, very fine-grained model incorporating the spatial distribution of population into geographical settlements, with a hierarchical organization down to the level of households (inside which we assume homogeneous mixing). In addition, population is organized heterogeneously outside households, and we model the movement of individuals using travel distance and frequency parameters for inter- and intra-settlement movement. Discrete event simulation, employing an adapted SIR model with relapse, reproduces important qualitative characteristics of real epidemics, like high variation in size and temporal heterogeneity (e.g., waves), that are challenging to reproduce and to quantify with existing measures. Our results pinpoint an important aspect, that epidemic size is more sensitive to the increase in distance of travel, rather that the frequency of travel. Finally, we discuss implications for the control of epidemics by integrating human mobility restrictions, as well as progressive vaccination of individuals.


Assuntos
COVID-19/epidemiologia , Doenças Transmissíveis/epidemiologia , Influenza Humana/epidemiologia , COVID-19/virologia , Doenças Transmissíveis/virologia , Simulação por Computador , Epidemias/prevenção & controle , Epidemias/estatística & dados numéricos , Características da Família , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/virologia , SARS-CoV-2/patogenicidade , Viagem/estatística & dados numéricos
4.
Nat Commun ; 12(1): 4313, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262041

RESUMO

How a history of influenza virus infections contributes to protection is not fully understood, but such protection might explain the contrasting age distributions of cases of the two lineages of influenza B, B/Victoria and B/Yamagata. Fitting a statistical model to those distributions using surveillance data from New Zealand, we found they could be explained by historical changes in lineage frequencies combined with cross-protection between strains of the same lineage. We found additional protection against B/Yamagata in people for whom it was their first influenza B infection, similar to the immune imprinting observed in influenza A. While the data were not informative about B/Victoria imprinting, B/Yamagata imprinting could explain the fewer B/Yamagata than B/Victoria cases in cohorts born in the 1990s and the bimodal age distribution of B/Yamagata cases. Longitudinal studies can test if these forms of protection inferred from historical data extend to more recent strains and other populations.


Assuntos
Vírus da Influenza B/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Distribuição por Idade , Proteção Cruzada , Humanos , Memória Imunológica , Vírus da Influenza B/classificação , Influenza Humana/virologia , Modelos Estatísticos , Nova Zelândia/epidemiologia , Probabilidade
5.
Nat Commun ; 12(1): 4427, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285233

RESUMO

The membrane-associated RING-CH (MARCH) proteins are E3 ligases that regulate the stability of various cellular membrane proteins. MARCH8 has been reported to inhibit the infection of HIV-1 and a few other viruses, thus plays an important role in host antiviral defense. However, the antiviral spectrum and the underlying mechanisms of MARCH8 are incompletely defined. Here, we demonstrate that MARCH8 profoundly inhibits influenza A virus (IAV) replication both in vitro and in mice. Mechanistically, MARCH8 suppresses IAV release through redirecting viral M2 protein from the plasma membrane to lysosomes for degradation. Specifically, MARCH8 catalyzes the K63-linked polyubiquitination of M2 at lysine residue 78 (K78). A recombinant A/Puerto Rico/8/34 virus carrying the K78R M2 protein shows greater replication and more severe pathogenicity in cells and mice. More importantly, we found that the M2 protein of the H1N1 IAV has evolved to acquire non-lysine amino acids at positions 78/79 to resist MARCH8-mediated ubiquitination and degradation. Together, our data support the important role of MARCH8 in host anti-IAV intrinsic immune defense by targeting M2, and suggest the inhibitory pressure of MARCH8 on H1N1 IAV transmission in the human population.


Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Ubiquitina-Proteína Ligases/metabolismo , Proteínas da Matriz Viral/metabolismo , Células A549 , Sequência de Aminoácidos , Animais , Modelos Animais de Doenças , Cães , Técnicas de Silenciamento de Genes , Células HEK293 , Células HeLa , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/metabolismo , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/virologia , Lisina/genética , Lisina/metabolismo , Lisossomos/metabolismo , Lisossomos/virologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Ubiquitina-Proteína Ligases/genética , Ubiquitinação/genética , Ubiquitinação/imunologia , Proteínas da Matriz Viral/genética , Replicação Viral
7.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071094

RESUMO

Three main approaches are used to combat severe viral respiratory infections. The first is preemptive vaccination that blocks infection. Weakened or dead viral particles, as well as genetic constructs carrying viral proteins or information about them, are used as an antigen. However, the viral genome is very evolutionary labile and changes continuously. Second, chemical agents are used during infection and inhibit the function of a number of viral proteins. However, these drugs lose their effectiveness because the virus can rapidly acquire resistance to them. The third is the search for points in the host metabolism the effect on which would suppress the replication of the virus but would not have a significant effect on the metabolism of the host. Here, we consider the possibility of using the copper metabolic system as a target to reduce the severity of influenza infection. This is facilitated by the fact that, in mammals, copper status can be rapidly reduced by silver nanoparticles and restored after their cancellation.


Assuntos
Cobre/metabolismo , Vírus da Influenza A/fisiologia , Influenza Humana/metabolismo , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Ceruloplasmina/fisiologia , Proteínas de Transporte de Cobre/metabolismo , ATPases Transportadoras de Cobre/fisiologia , Farmacorresistência Viral , Interações Hospedeiro-Patógeno , Humanos , Vacinas contra Influenza , Influenza Humana/tratamento farmacológico , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Mamíferos/metabolismo , Nanopartículas Metálicas/uso terapêutico , Chaperonas Moleculares/metabolismo , Proteínas PrPC/fisiologia , RNA Viral/fisiologia , Prata/uso terapêutico , Superóxido Dismutase-1/fisiologia , Proteínas Virais/fisiologia , Replicação Viral
8.
PLoS One ; 16(6): e0253451, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34143839

RESUMO

BACKGROUND: Various public health measures have been implemented globally to counter the coronavirus disease 2019 (COVID-19) pandemic. The purpose of this study was to evaluate respiratory virus surveillance data to determine the effectiveness of such interventions in reducing transmission of seasonal respiratory viruses. METHOD: We retrospectively analysed data from the Respiratory Virus Detection Surveillance System in Canada, before and during the COVID-19 pandemic, by interrupted time series regression. RESULTS: The national level of infection with seasonal respiratory viruses, which generally does not necessitate quarantine or contact screening, was greatly reduced after Canada imposed physical distancing and other quarantine measures. The 2019-2020 influenza season ended earlier than it did in the previous year. The influenza virus was replaced by rhinovirus/enterovirus or parainfluenza virus in the previous year, with the overall test positivity remaining at approximately 35%. However, during the 2019-2020 post-influenza period, the overall test positivity of respiratory viruses during the COVID-19 was still low (7.2%). Moreover, the 2020-2021 influenza season had not occurred by the end of February 2021. CONCLUSION: Respiratory virus surveillance data may provide real-world evidence of the effectiveness of implemented public health interventions during the current and future pandemics.


Assuntos
COVID-19/prevenção & controle , Análise de Séries Temporais Interrompida/métodos , Vigilância da População/métodos , Saúde Pública/métodos , SARS-CoV-2/isolamento & purificação , COVID-19/epidemiologia , COVID-19/virologia , Canadá/epidemiologia , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Análise de Séries Temporais Interrompida/estatística & dados numéricos , Modelos Estatísticos , Pandemias , Distanciamento Físico , Saúde Pública/estatística & dados numéricos , Quarentena , Estudos Retrospectivos , SARS-CoV-2/fisiologia , Estações do Ano , Vírus/classificação
9.
Life Sci ; 280: 119744, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34174324

RESUMO

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.


Assuntos
Nanopartículas/química , Polímeros/química , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/virologia , Vacinação , Vacinas Virais/administração & dosagem , Animais , COVID-19/prevenção & controle , COVID-19/virologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Portadores de Fármacos/química , Humanos , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/virologia , Vacinação/métodos , Vacinas Virais/uso terapêutico
10.
Sci Rep ; 11(1): 12703, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135459

RESUMO

Secondary bacterial infections are a potentially fatal complication of influenza infection. We aimed to define the impact of secondary bacterial infections on the clinical course and mortality in coronavirus disease 2019 (COVID-19) patients by comparison with influenza patients. COVID-19 (n = 642) and influenza (n = 742) patients, admitted to a large tertiary center in Israel and for whom blood or sputum culture had been taken were selected for this study. Bacterial culture results, clinical parameters, and death rates were compared. COVID-19 patients had higher rates of bacterial infections than influenza patients (12.6% vs. 8.7%). Notably, the time from admission to bacterial growth was longer in COVID-19 compared to influenza patients (4 (1-8) vs. 1 (1-3) days). Late infections (> 48 h after admission) with gram-positive bacteria were more common in COVID-19 patients (28% vs. 9.5%). Secondary infection was associated with a higher risk of death in both patient groups 2.7-fold (1.22-5.83) for COVID-19, and 3.09-fold (1.11-7.38) for Influenza). The association with death remained significant upon adjustment to age and clinical parameters in COVID-19 but not in influenza infection. Secondary bacterial infection is a notable complication associated with worse outcomes in COVID-19 than influenza patients. Careful surveillance and prompt antibiotic treatment may benefit selected patients.


Assuntos
COVID-19/epidemiologia , COVID-19/mortalidade , Coinfecção/epidemiologia , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/epidemiologia , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/epidemiologia , Vírus da Influenza A/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/mortalidade , Pandemias , SARS-CoV-2/isolamento & purificação , Adulto , Idoso , COVID-19/virologia , Coinfecção/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Influenza Humana/virologia , Israel/epidemiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Estudos Retrospectivos
11.
Sci Rep ; 11(1): 12948, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155232

RESUMO

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was "double-stranded RNA binding" and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.


Assuntos
Adenocarcinoma/etiologia , COVID-19/complicações , Carcinogênese/genética , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Neoplasias Pancreáticas/etiologia , Vírus da SARS , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/complicações , COVID-19/genética , COVID-19/metabolismo , COVID-19/virologia , Caspase 3/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Influenza Humana/genética , Influenza Humana/metabolismo , Influenza Humana/virologia , PTEN Fosfo-Hidrolase/genética , Mapas de Interação de Proteínas , Risco , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/metabolismo , Síndrome Respiratória Aguda Grave/virologia , Transdução de Sinais/genética , Proteína Smad3/genética , Regulação para Cima/genética
12.
BMC Infect Dis ; 21(1): 617, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187397

RESUMO

BACKGROUND: Seasonal influenza leads to significant morbidity and mortality. Rapid self-tests could improve access to influenza testing in community settings. We aimed to evaluate the diagnostic accuracy of a mobile app-guided influenza rapid self-test for adults with influenza like illness (ILI), and identify optimal methods for conducting accuracy studies for home-based assays for influenza and other respiratory viruses. METHODS: This cross-sectional study recruited adults who self-reported ILI online. Participants downloaded a mobile app, which guided them through two low nasal swab self-samples. Participants tested the index swab using a lateral flow assay. Test accuracy results were compared to the reference swab tested in a research laboratory for influenza A/B using a molecular assay. RESULTS: Analysis included 739 participants, 80% were 25-64 years of age, 79% female, and 73% white. Influenza positivity was 5.9% based on the laboratory reference test. Of those who started their test, 92% reported a self-test result. The sensitivity and specificity of participants' interpretation of the test result compared to the laboratory reference standard were 14% (95%CI 5-28%) and 90% (95%CI 87-92%), respectively. CONCLUSIONS: A mobile app facilitated study procedures to determine the accuracy of a home based test for influenza, however, test sensitivity was low. Recruiting individuals outside clinical settings who self-report ILI symptoms may lead to lower rates of influenza and/or less severe disease. Earlier identification of study subjects within 48 h of symptom onset through inclusion criteria and rapid shipping of tests or pre-positioning tests is needed to allow self-testing earlier in the course of illness, when viral load is higher.


Assuntos
Vírus da Influenza A/imunologia , Vírus da Influenza B/imunologia , Influenza Humana/diagnóstico , Aplicativos Móveis , Autoteste , Adulto , Estudos Transversais , Confiabilidade dos Dados , Ensaio de Imunoadsorção Enzimática/métodos , Estudos de Viabilidade , Feminino , Humanos , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
13.
Nat Commun ; 12(1): 3249, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059675

RESUMO

Coronavirus disease 2019 (COVID-19) was detected in China during the 2019-2020 seasonal influenza epidemic. Non-pharmaceutical interventions (NPIs) and behavioral changes to mitigate COVID-19 could have affected transmission dynamics of influenza and other respiratory diseases. By comparing 2019-2020 seasonal influenza activity through March 29, 2020 with the 2011-2019 seasons, we found that COVID-19 outbreaks and related NPIs may have reduced influenza in Southern and Northern China and the United States by 79.2% (lower and upper bounds: 48.8%-87.2%), 79.4% (44.9%-87.4%) and 67.2% (11.5%-80.5%). Decreases in influenza virus infection were also associated with the timing of NPIs. Without COVID-19 NPIs, influenza activity in China and the United States would likely have remained high during the 2019-2020 season. Our findings provide evidence that NPIs can partially mitigate seasonal and, potentially, pandemic influenza.


Assuntos
COVID-19/epidemiologia , Influenza Humana/epidemiologia , Modelos Estatísticos , Pandemias , Infecções Respiratórias/epidemiologia , COVID-19/transmissão , COVID-19/virologia , China/epidemiologia , Humanos , Influenza Humana/transmissão , Influenza Humana/virologia , Orthomyxoviridae/patogenicidade , Orthomyxoviridae/fisiologia , Equipamento de Proteção Individual , Distanciamento Físico , Quarentena/organização & administração , Infecções Respiratórias/transmissão , Infecções Respiratórias/virologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Estações do Ano , Estados Unidos/epidemiologia
15.
Med Sci Monit ; 27: e929572, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33994536

RESUMO

BACKGROUND Obesity is associated with susceptibility to severe influenza infection and several disturbances of the immune response to the influenza vaccine. However, the effect of obesity on the immunogenicity of the influenza vaccine is not fully understood. Our objective here was to assess the immunogenicity of the split, inactivated quadrivalent influenza vaccine (QIV) in Polish adults with obesity. MATERIAL AND METHODS Fifty-three subjects with obesity aged 21-69 years were vaccinated with the QIV in 2017/2018 season. Antibody titers against the 4 vaccine strains were measured using the hemagglutination inhibition (HI) assay. The mean fold antibody increase (MFI), seroprotection rate (protection rate, PR), and seroconversion rate (response rate, RR) were calculated to assess vaccine immunogenicity. RESULTS The vaccine elicited a significant increase in the anti-HI titers against the QIV antigens. The MFI, PR, and RR for the QIV antigens also reached the required age-specific values, indicating the QIV meets current immunogenicity criteria. Individuals with class I and class II/III obesity had similar anti-HI titers, MFI, PR, and RR to each of the vaccine strains. Adults aged <60 years had similar anti-HI titers, MFI, PR, and RR to the QIV strains to those aged ≥60 years. CONCLUSIONS Our results indicate that the split virion, inactivated QIV is immunogenic in adults with obesity regardless of their degree of obesity and age (ie, <60 and ≥60 years).


Assuntos
Imunogenicidade da Vacina/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Obesidade/imunologia , Adulto , Idoso , Anticorpos Antivirais/imunologia , Feminino , Humanos , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Obesidade/virologia , Estações do Ano , Soroconversão/fisiologia , Adulto Jovem
16.
Sci Rep ; 11(1): 10793, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031464

RESUMO

Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expression analysis. Here, we developed an alternative approach that could be applied to dissect the disease-associated molecular changes. We define gene ensemble noise as a measure that represents a variance for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes and calculated within an individual. The gene ensemble noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. By comparing gene expression data from COVID-19, H1N1, and sepsis patients we identified common disturbances in a number of pathways and protein complexes relevant to the sepsis pathology. Among others, these include the mitochondrial respiratory chain complex I and peroxisomes. This suggests a Warburg effect and oxidative stress as common hallmarks of the immune host-pathogen response. Finally, we showed that gene ensemble noise could successfully be applied for the prediction of clinical outcome namely, the mortality of patients. Thus, we conclude that gene ensemble noise represents a promising approach for the investigation of molecular mechanisms of pathology through a prism of alterations in the coherent expression of gene circuits.


Assuntos
COVID-19/patologia , Expressão Gênica , Influenza Humana/patologia , Sepse/patologia , Área Sob a Curva , COVID-19/complicações , COVID-19/virologia , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Redes Reguladoras de Genes/genética , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/complicações , Influenza Humana/virologia , Estresse Oxidativo/genética , Peroxissomos/genética , Peroxissomos/metabolismo , Modelos de Riscos Proporcionais , Curva ROC , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sepse/complicações , Sepse/genética , Sepse/mortalidade , Índice de Gravidade de Doença , Taxa de Sobrevida , Interface Usuário-Computador
17.
Nat Commun ; 12(1): 2931, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006841

RESUMO

Indigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in Indigenous populations, is associated with influenza-induced mortality, although the basis for this association is unclear. Here, we define CD8+ T-cell immune landscapes against influenza A (IAV) and B (IBV) viruses in HLA-A*24:02-expressing Indigenous and non-Indigenous individuals, human tissues, influenza-infected patients and HLA-A*24:02-transgenic mice. We identify immunodominant protective CD8+ T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2550-558-specific CD8+ T cells being cross-reactive between IAV and IBV. Memory CD8+ T cells towards these specificities are present in blood (CD27+CD45RA- phenotype) and tissues (CD103+CD69+ phenotype) of healthy individuals, and effector CD27-CD45RA-PD-1+CD38+CD8+ T cells in IAV/IBV patients. Our data show influenza-specific CD8+ T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8+ T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Epitopos de Linfócito T/genética , Antígeno HLA-A24/genética , Povos Indígenas/genética , Adulto , Alelos , Sequência de Aminoácidos , Animais , Austrália , Linfócitos T CD8-Positivos/imunologia , Células Cultivadas , Cães , Epitopos de Linfócito T/imunologia , Feminino , Frequência do Gene , Antígeno HLA-A24/imunologia , Humanos , Vírus da Influenza A/imunologia , Vírus da Influenza A/fisiologia , Vírus da Influenza B/imunologia , Vírus da Influenza B/fisiologia , Influenza Humana/imunologia , Influenza Humana/virologia , Masculino , Camundongos Transgênicos , Pessoa de Meia-Idade
19.
Clin Dermatol ; 39(1): 5-8, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33972052

RESUMO

Pandemics have ravished the globe periodically, often associated with war, at times commencing as fever and rash, beginning in recorded history in the crowded walled city of Athens during the Peloponnesian War as described in great detail by the Athenian historian and military general Thucydides in 430 BCE. As the world now faces the first major pandemic of the 21st century, we focus on the "plague" commencing in Athens in 430 BCE and the 2 pandemics of the more recent century, which killed more than one million, the Spanish flu of 1918 and the Asian flu of 1957. The latter linked with successful vaccine development thanks to the heroic efforts of microbiologist Maurice Hilleman. We now look back and then forward to the viral infection coronavirus disease 2019 now devastating the world.


Assuntos
Influenza Pandêmica, 1918-1919/história , Influenza Humana/história , Pandemias/história , Conflitos Armados/história , Ásia , Grécia , História Antiga , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia
20.
Can J Public Health ; 112(4): 620-628, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34047965

RESUMO

OBJECTIVES: Seasonal influenza is an acute respiratory infection that presents a significant annual burden to Canadians and the Canadian healthcare system. Social distancing measures that were implemented to control the 2019-2020 novel coronavirus outbreak were investigated for their ability to lessen the incident cases of seasonal influenza. METHODS: We conducted an ecological study using data from Canada's national influenza surveillance system to investigate whether social distancing measures to control COVID-19 reduced the incident cases of seasonal influenza. Data taken from three separate time frames facilitated analysis of the 2019-2020 influenza season prior to, during, and following the implementation of COVID-19-related measures and enabled comparisons with the same time periods during three preceding flu seasons. The incidence, which referred to the number of laboratory-confirmed cases of specific influenza strains, was of primary focus. Further analysis determined the number of new laboratory-confirmed influenza or influenza-like illness outbreaks. RESULTS: Our results indicate a premature end to the 2019-2020 influenza season, with significantly fewer cases and outbreaks being recorded following the enactment of many COVID-19 social distancing policies. The incidence of influenza strains A (H3N2), A (unsubtyped), and B were all significantly lower at the tail end of the 2019-2020 influenza season as compared with preceding seasons (p = 0.0003, p = 0.0007, p = 0.0019). CONCLUSION: Specific social distancing measures and behaviours may serve as effective tools to limit the spread of influenza transmission moving forward, as they become more familiar.


Assuntos
COVID-19/prevenção & controle , Influenza Humana/epidemiologia , Distanciamento Físico , Vigilância em Saúde Pública , COVID-19/epidemiologia , Canadá/epidemiologia , Humanos , Incidência , Influenza Humana/virologia , Estações do Ano
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