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1.
Front Immunol ; 12: 629193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732251

RESUMO

Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.


Assuntos
/imunologia , Síndrome da Liberação de Citocina/imunologia , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Índice de Gravidade de Doença , /sangue , /virologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/virologia , Citocinas/sangue , Humanos , Inflamação/imunologia , Influenza Humana/sangue , Influenza Humana/virologia , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/virologia
2.
Nat Commun ; 12(1): 1722, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741916

RESUMO

Broadly neutralizing antibodies (bnAbs) have been developed as potential countermeasures for seasonal and pandemic influenza. Deep characterization of these bnAbs and polyclonal sera provides pivotal understanding for influenza immunity and informs effective vaccine design. However, conventional virus neutralization assays require high-containment laboratories and are difficult to standardize and roboticize. Here, we build a panel of engineered influenza viruses carrying a reporter gene to replace an essential viral gene, and develop an assay using the panel for in-depth profiling of neutralizing antibodies. Replication of these viruses is restricted to cells expressing the missing viral gene, allowing it to be manipulated in a biosafety level 2 environment. We generate the neutralization profile of 24 bnAbs using a 55-virus panel encompassing the near-complete diversity of human H1N1 and H3N2, as well as pandemic subtype viruses. Our system offers in-depth profiling of influenza immunity, including the antibodies against the hemagglutinin stem, a major target of universal influenza vaccines.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vírus da Influenza A/imunologia , Influenza Humana/virologia , Antígenos Virais/imunologia , Perfilação da Expressão Gênica , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Hemaglutininas , Humanos , Imunidade , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A/genética , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/virologia , Filogenia
3.
PLoS One ; 16(2): e0247605, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33635872

RESUMO

Neutrophils participate in the early phase of the innate response to uncomplicated influenza A virus (IAV) infection but also are a major component in later stages of severe IAV or COVID 19 infection where neutrophil extracellular traps (NETs) and associated cell free histones are highly pro-inflammatory. It is likely that IAV interacts with histones during infection. We show that histone H4 binds to IAV and aggregates viral particles. In addition, histone H4 markedly potentiates IAV induced neutrophil respiratory burst responses. Prior studies have shown reactive oxidants to be detrimental during severe IAV infection. C reactive protein (CRP) and surfactant protein D (SP-D) rise during IAV infection. We now show that both of these innate immune proteins bind to histone H4 and significantly down regulate respiratory burst and other responses to histone H4. Isolated constructs composed only of the neck and carbohydrate recognition domain of SP-D also bind to histone H4 and partially limit neutrophil responses to it. These studies indicate that complexes formed of histones and IAV are a potent neutrophil activating stimulus. This finding could account for excess inflammation during IAV or other severe viral infections. The ability of CRP and SP-D to bind to histone H4 may be part of a protective response against excessive inflammation in vivo.


Assuntos
Proteína C-Reativa/imunologia , Histonas/imunologia , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Neutrófilos/imunologia , Proteína D Associada a Surfactante Pulmonar/imunologia , Células Cultivadas , Humanos , Imunidade Inata , Inflamação/etiologia , Inflamação/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Influenza Humana/complicações
4.
Arch Virol ; 166(4): 1197-1201, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33598814

RESUMO

Waterfowl are considered to be the natural hosts of avian influenza virus. In 2017, two reassortant highly pathogenic H5N6 avian influenza viruses of clade 2.3.4.4, subclade II, were identified in wild birds in eastern China. Genome sequencing and phylogenetic and antigenicity analysis showed that the viruses originated from multiple reassortments. To evaluate their pathogenicity in mammals, 15 BALB/c mice were infected with these viruses, and survival and weight loss were monitored for 14 days. Infection was associated with moderate pathogenicity in the mice, and the viruses could replicate in the lungs without prior adaptation. Thus, the existence of these viruses poses a continuous threat to both birds and humans.


Assuntos
Animais Selvagens/virologia , Aves/virologia , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/virologia , Vírus Reordenados/isolamento & purificação , Animais , China/epidemiologia , Variação Genética , Genoma Viral/genética , Genótipo , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Vírus da Influenza A/patogenicidade , Camundongos , Camundongos Endogâmicos BALB C , Filogenia , RNA Viral/genética , Vírus Reordenados/genética , Vírus Reordenados/imunologia , Vírus Reordenados/patogenicidade , Proteínas Virais/genética , Proteínas Virais/imunologia
5.
Arch Virol ; 166(4): 1113-1124, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33576898

RESUMO

Avian influenza virus (AIV), Newcastle disease virus (NDV), and avian infectious bronchitis virus (IBV) inflict immense damage on the global poultry industry annually. Serological diagnostic methods are fundamental for the effective control and prevention of outbreaks caused by these viruses. In this study, a novel triplex protein microarray assay was developed and validated for the rapid and simultaneous visualized detection of antibodies against AIV, NDV, and IBV in chicken sera. The AIV nuclear protein (NP), NDV phosphoprotein (P), and IBV nonstructural protein 5 (nsp5) were produced in a prokaryotic expression system, purified, and immobilized onto an initiator integrated poly(dimethylsiloxane) (iPDMS) film as probes to detect antibodies against these viruses in chicken sera. After optimization of the reaction conditions, no cross-reactivity was detected with infectious bursal disease virus, avian leukosis virus subgroup J and chicken anemia virus antisera. The lowest detectable antibody titers in this assay corresponded to hemagglutination inhibition (HI) titers of 24 and 21 for AIV and NDV, respectively, and to an IDEXX antibody titer of 103 for IBV, using the HI assay and IDEXX commercial ELISA kit as the reference methods. When156 serum samples were tested using the new assay, the HI test and the IBV IDEXX ELISA kit, the assay showed 96.8% (151/156), 97.4% (152/156) and 99.4% (155/156) diagnostic accuracy for detection of AIV, NDV and IBV antibody, respectively. The current study suggests that the newly developed triplex microarray is rapid, sensitive, and specific, providing a viable alternative assay for AIV, NDV, and IBV antibody screening in epidemiological investigations and vaccination evaluations.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Bronquite Infecciosa/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Vírus da Doença de Newcastle/isolamento & purificação , Doenças das Aves Domésticas/diagnóstico , Análise Serial de Proteínas/veterinária , Animais , Antígenos Virais/genética , Antígenos Virais/imunologia , Antígenos Virais/metabolismo , Galinhas , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/veterinária , Imunoensaio/normas , Imunoensaio/veterinária , Vírus da Bronquite Infecciosa/imunologia , Vírus da Influenza A/imunologia , Influenza Aviária/diagnóstico , Doença de Newcastle/diagnóstico , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/virologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Sensibilidade e Especificidade , Testes Sorológicos/normas , Testes Sorológicos/veterinária
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.
Viruses ; 13(2)2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33494528

RESUMO

Natural killer (NK) cells are part of the innate immunity repertoire, and function in the recognition and destruction of tumorigenic and pathogen-infected cells. Engagement of NK cell activating receptors can lead to functional activation of NK cells, resulting in lysis of target cells. NK cell activating receptors specific for non-major histocompatibility complex ligands are NKp46, NKp44, NKp30, NKG2D, and CD16 (also known as FcγRIII). The natural cytotoxicity receptors (NCRs), NKp46, NKp44, and NKp30, have been implicated in functional activation of NK cells following influenza virus infection via binding with influenza virus hemagglutinin (HA). In this review we describe NK cell and influenza A virus biology, and the interactions of influenza A virus HA and other pathogen lectins with NK cell natural cytotoxicity receptors (NCRs). We review concepts which intersect viral immunology, traditional virology and glycobiology to provide insights into the interactions between influenza virus HA and the NCRs. Furthermore, we provide expert opinion on future directions that would provide insights into currently unanswered questions.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A/imunologia , Células Matadoras Naturais/imunologia , Receptor 1 Desencadeador da Citotoxicidade Natural/imunologia , Receptor 2 Desencadeador da Citotoxicidade Natural/imunologia , Receptor 3 Desencadeador da Citotoxicidade Natural/imunologia , Proteínas Ligadas por GPI/imunologia , Humanos , Receptores de IgG/imunologia
8.
Viruses ; 13(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477472

RESUMO

Influenza A Viruses (IAV) in domestic swine (IAV-S) are associated with sporadic zoonotic transmission at the human-animal interface. Previous pandemic IAVs originated from animals, which emphasizes the importance of characterizing human immunity against the increasingly diverse IAV-S. We analyzed serum samples from healthy human donors (n = 153) using hemagglutination-inhibition (HAI) assay to assess existing serologic protection against a panel of contemporary IAV-S isolated from swine in the United States (n = 11). Age-specific seroprotection rates (SPR), which are the proportion of individuals with HAI ≥ 1:40, corresponded with lower or moderate pandemic risk classifications for the multiple IAV-S examined (one H1-δ1, one H1-δ2, three H3-IVA, one H3-IVB, one H3-IVF). Individuals born between 2004 and 2013 had SPRs of 0% for the five classified H3 subtype IAV-S, indicating youth may be particularly predisposed to infection with these viruses. Expansion of existing immunologic gaps over time could increase likelihood of future IAV-S spillover to humans and facilitate subsequent sustained human-to-human transmission resulting in disease outbreaks with pandemic potential.


Assuntos
Vírus da Influenza A/imunologia , Influenza Humana/epidemiologia , Influenza Humana/transmissão , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/imunologia , Adulto , Idoso , Animais , Feminino , Humanos , Vírus da Influenza A/classificação , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Estações do Ano , Testes Sorológicos , Suínos , Doenças dos Suínos/virologia , Estados Unidos/epidemiologia
9.
Arch Virol ; 166(2): 571-579, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410993

RESUMO

This study compared concurrent and separate primary vaccination against equid alphaherpesviruses 1 and 4, genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae, and equine influenza A virus, genus Alphainfluenzavirus, family Orthomyxoviridae. Their vernacular names are equine herpesvirus 1 and 4 (EHV1/4) and equine influenza virus (EIV). Infection with these respiratory pathogens is associated with loss of performance, interruption of training schedules, and on occasion, cancellation of equestrian events. Vaccination is highly recommended, and for some activities it is a mandatory requirement of the relevant authority. As there is a dearth of information relating to the impact of concurrent vaccination on the antibody response to EHV and EIV vaccines, they are usually administered separately, often 2 weeks apart. In a previous study of booster vaccination in Thoroughbred racehorses, concurrent vaccination with whole-virus inactivated carbopol-adjuvanted EHV and EIV vaccines did not impact negatively on the antibody response. In this study, investigations were extended to concurrent versus separate primary vaccination of warmblood foals. A field study was conducted to compare the immune response to a carbopol-adjuvanted EHV vaccine and an immune stimulating complex (ISCOM)-adjuvanted EI vaccine administered concurrently and 2 weeks apart. No adverse clinical reactions were observed, the pattern of EI and EHV antibody response was similar for both groups, and there was no evidence that concurrent primary vaccination compromised the humoral response. The results are of relevance to horse owners who wish to decrease veterinary costs, limit handling of young animals, and simplify record keeping by vaccinating concurrently.


Assuntos
Infecções por Herpesviridae/imunologia , Vacinas contra Herpesvirus/imunologia , Doenças dos Cavalos/imunologia , Cavalos/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Feminino , Doenças dos Cavalos/virologia , Cavalos/virologia , Imunidade Humoral/imunologia , Imunização Secundária/métodos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Vacinação/métodos , Vacinas de Produtos Inativados/imunologia
10.
Nat Commun ; 12(1): 559, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495478

RESUMO

Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among VH3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of VH3-30 antibodies and reveals that 3I14 represents a novel structural solution within the VH3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Epitopos/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A/imunologia , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/metabolismo , Epitopos/química , Epitopos/metabolismo , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Vírus da Influenza A/metabolismo , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/virologia
11.
Methods Mol Biol ; 2241: 99-112, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33486731

RESUMO

Eosinophils are granulocytes that were historically considered to be terminally differentiated at the time of bone marrow egress. However, more recent evidence provides a new outlook on these cells as complex immunomodulators that are involved in host defense and homeostasis. Our work established a role for eosinophils as mediators of antiviral immune responses during influenza in hosts that were sensitized and challenged with fungal allergens. Herein, we describe methods for working with murine eosinophils in the context of influenza A virus.


Assuntos
Eosinófilos/citologia , Micoses/imunologia , Viroses/imunologia , Alérgenos , Animais , Asma/imunologia , Modelos Animais de Doenças , Cães , Eosinófilos/imunologia , Vírus da Influenza A/imunologia , Vírus da Influenza A/patogenicidade , Contagem de Leucócitos , Células Madin Darby de Rim Canino , Camundongos
12.
Vet Res ; 52(1): 8, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33436086

RESUMO

Since 2014, clade 2.3.4.4 has become the dominant epidemic branch of the Asian lineage H5 subtype highly pathogenic avian influenza virus (HPAIV) in southern and eastern China, while the H5N6 subtype is the most prevalent. We have shown earlier that lack of glycosylation at position 158 of the hemagglutinin (HA) glycoprotein due to the T160A mutation is a key determinant of the dual receptor binding property of clade 2.3.4.4 H5NX subtypes. Our present study aims to explore other effects of this site among H5N6 viruses. Here we report that N-linked glycosylation at site 158 facilitated the assembly of virus-like particles and enhanced virus replication in A549, MDCK, and chicken embryonic fibroblast (CEF) cells. Consistently, the HA-glycosylated H5N6 virus induced higher levels of inflammatory factors and resulted in stronger pathogenicity in mice than the virus without glycosylation at site 158. However, H5N6 viruses without glycosylation at site 158 were more resistant to heat and bound host cells better than the HA-glycosylated viruses. H5N6 virus without glycosylation at this site triggered the host immune response mechanism to antagonize the viral infection, making viral pathogenicity milder and favoring virus spread. These findings highlight the importance of glycosylation at site 158 of HA for the pathogenicity of the H5N6 viruses.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A/metabolismo , Influenza Aviária/virologia , Células A549/virologia , Animais , Embrião de Galinha/virologia , Galinhas , Glicosilação , Testes de Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/fisiologia , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Vírus da Influenza A/fisiologia , Influenza Aviária/imunologia , Influenza Humana/imunologia , Influenza Humana/virologia , Reação em Cadeia da Polimerase em Tempo Real
13.
Science ; 371(6526): 271-276, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33446553

RESUMO

Type I interferon (IFN) signaling in fetal tissues causes developmental abnormalities and fetal demise. Although pathogens that infect fetal tissues can induce birth defects through the local production of type I IFN, it remains unknown why systemic IFN generated during maternal infections only rarely causes fetal developmental defects. Here, we report that activation of the guanine nucleotide-binding protein-coupled estrogen receptor 1 (GPER1) during pregnancy is both necessary and sufficient to suppress IFN signaling and does so disproportionately in reproductive and fetal tissues. Inactivation of GPER1 in mice halted fetal development and promoted fetal demise, but only in the context of maternal inflammation. Thus, GPER1 is a central regulator of IFN signaling during pregnancy that allows dynamic antiviral responses in maternal tissues while also preserving fetal health.


Assuntos
Doenças Fetais/imunologia , Inflamação/imunologia , Troca Materno-Fetal/imunologia , Complicações Infecciosas na Gravidez/imunologia , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Benzodioxóis/farmacologia , Sistemas CRISPR-Cas , Feminino , Doenças Fetais/virologia , Feto/imunologia , Feto/virologia , Humanos , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Interferon Tipo I/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Placenta/imunologia , Placenta/virologia , Gravidez , Quinolinas/farmacologia , Receptores Estrogênicos/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/antagonistas & inibidores
14.
Esc. Anna Nery Rev. Enferm ; 25(spe): e20200379, 2021. graf
Artigo em Português | LILACS, BDENF - Enfermagem | ID: biblio-1148333

RESUMO

Objetivo: descrever a experiência de integração ensino-serviço durante a primeira etapa da 22ª Campanha Nacional de Vacinação contra a Influenza na emergência da COVID-19. Método: relato de experiência sobre a parceria de um curso de enfermagem de uma das instituições de ensino superior de Ribeirão Preto-SP, Brasil, com serviços da Atenção Primária à Saúde na referida campanha, no período de março a abril de 2020. Resultados: essa parceria mobilizou diversos voluntários para implementar 35 postos volantes de vacinação, incluindo um drive-thru. Nessa primeira etapa, foram aplicadas 91.697 doses do imunobiológico em idosos, de um total de 98.189, que correspondeu a 83,3%, valor muito próximo da cobertura vacinal de 90% esperada para esse grupo populacional. Com a parceria, o número total de doses aplicadas em idosos ao final da 22a campanha, na cidade, superou em 42,6% a média dos últimos cinco anos. Conclusão e implicações para a prática: atribui-se esse percentual ao trabalho coletivo e multiprofissional e ao compromisso social das instituições envolvidas com a proteção da saúde, a preservação da vida e o fortalecimento do Sistema Único de Saúde.


Objective: to describe the experience of teaching-service integration during the first stage of the 22nd Brazilian National Influenza Vaccination Campaign in the emergence of COVID-19. Method: this is an experience report on the partnership of a nursing course from one of the higher education institutions in Ribeirão Preto-SP, Brazil, with Primary Health Care services in that campaign, from March to April 2020. Results: this partnership mobilized several volunteers to implement 35 vaccination stations, including a drive-thru. In this first stage, 91,697 doses of the immunobiological agent were applied to older adults, from a total of 98,189, which corresponded to 83.3%, a value very close to the 90% vaccination coverage expected for this population group. With the partnership, the total number of doses applied to older adults at the end of the 22nd campaign in the city exceeded the average of the last five years by 42.6%. Conclusion and implications for practice: this percentage is attributed to the collective and multiprofessional work and the social commitment of the institutions involved with protection of health, preservation of life and strengthening of the Unified Health System.


Objetivo: describir la experiencia de integración enseñanza-servicio durante la primera etapa de la 22ª Campaña Nacional de Vacunación contra el Influenza en la emergencia de la covid-19. Método: un relato de experiencia de la asociación de un curso de enfermería de una institución de enseñanza superior de Ribeirão Preto-SP, Brasil con servicios de la atención primaria a la salud en la referida campaña, en el período de marzo a abril de 2020. Resultados: esta asociación movilizó a varios voluntarios para implementar 35 estaciones de vacunación, incluyendo un drive-thru. En esa primera etapa, fueron aplicadas 91.697 dosis del inmunobiológico en ancianos, de un total de 98.189, que correspondió a 83,3%, valor muy próximo de la cobertura vacunal de 90% esperada para ese grupo poblacional. Con la asociación, el número total de dosis aplicadas en ancianos al final de la 22a campaña en la ciudad superó en 42,6% el promedio de los últimos cinco años. Conclusión e implicaciones para la práctica: este porcentaje se atribuye al trabajo colectivo e interprofesional y al compromiso social de las instituciones involucradas con la protección de la salud, la preservación de la vida y el fortalecimiento del Sistema Único de Salud.


Assuntos
Humanos , Masculino , Feminino , Idoso , Vírus da Influenza A/imunologia , Atenção Primária à Saúde , Vacinas contra Influenza , Programas de Imunização , Influenza Humana/prevenção & controle , Pneumonia Viral/prevenção & controle , Infecções por Coronavirus/prevenção & controle , Educação em Enfermagem , Betacoronavirus
15.
BMJ Case Rep ; 13(12)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33370941

RESUMO

A 9-year-old girl was admitted to the paediatric intensive care unit with acute respiratory failure due to influenza. Nine months earlier, she presented with unexplained lymphoedema of the lower extremities and monocytopenia. She had a history of occasional finger warts and onychomycoses. During hospitalisation, the patient was diagnosed with Emberger syndrome caused by GATA2 deficiency. The admission was complicated by thromboses in the right hand, leading to amputation of multiple fingers. From then on, the patient has been in good recovery, the function of her right hand was improving and an allogeneic haematopoietic cell transplantation has now been successfully performed.


Assuntos
Dedos/patologia , Deficiência de GATA2/complicações , Fator de Transcrição GATA2/deficiência , Vírus da Influenza A/imunologia , /imunologia , Amputação , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Criança , Códon sem Sentido , Análise Mutacional de DNA , Quimioterapia Combinada , Feminino , Dedos/cirurgia , Deficiência de GATA2/diagnóstico , Deficiência de GATA2/genética , Deficiência de GATA2/imunologia , Fator de Transcrição GATA2/genética , Gangrena/imunologia , Gangrena/cirurgia , Glucocorticoides/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/complicações , Influenza Humana/imunologia , Influenza Humana/terapia , Influenza Humana/virologia , Pulmão/diagnóstico por imagem , Pulmão/imunologia , Respiração Artificial , /terapia , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
16.
JAMA Netw Open ; 3(12): e2030455, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33351086

RESUMO

Importance: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti-SARS-CoV-2 antibody, and incidence of fetoplacental infection. Design, Setting, and Participants: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription-polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2. Exposures: SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR. Main Outcomes and Measures: The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti-SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta. Results: Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti-receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti-SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti-receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted. Conclusions and Relevance: In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.


Assuntos
Anticorpos Antivirais/imunologia , Sangue Fetal/imunologia , Imunidade Materno-Adquirida/imunologia , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Placenta/metabolismo , Complicações Infecciosas na Gravidez/imunologia , /imunologia , Adulto , /sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Sangue Fetal/virologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Recém-Nascido , Vírus da Influenza A/imunologia , Masculino , Fosfoproteínas/imunologia , Placenta/patologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/sangue , Estudos Prospectivos , RNA Viral/metabolismo , Serina Endopeptidases/metabolismo , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia , Carga Viral
17.
Viruses ; 12(12)2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348840

RESUMO

Delivering rapid protection against infectious agents to non-immune populations is a formidable public health challenge. Although passive immunotherapy is a fast and effective method of protection, large-scale production and administration of monoclonal antibodies (mAbs) is expensive and unpractical. Viral vector-mediated delivery of mAbs offers an attractive alternative to their direct injection. Integrase-defective lentiviral vectors (IDLV) are advantageous for this purpose due to the absence of pre-existing anti-vector immunity and the safety features of non-integration and non-replication. We engineered IDLV to produce the humanized mAb VN04-2 (IDLV-VN04-2), which is broadly neutralizing against H5 influenza A virus (IAV), and tested the vectors' ability to produce antibodies and protect from IAV in vivo. We found that IDLV-transduced cells produced functional VN04-2 mAbs in a time- and dose-dependent fashion. These mAbs specifically bind the hemagglutinin (HA), but not the nucleoprotein (NP) of IAV. VN04-2 mAbs were detected in the serum of mice at different times after intranasal (i.n.) or intramuscular (i.m.) administration of IDLV-VN04-2. Administration of IDLV-VN04-2 by the i.n. route provided rapid protection against lethal IAV challenge, although the protection did not persist at later time points. Our data suggest that administration of mAb-expressing IDLV may represent an effective strategy for rapid protection against infectious diseases.


Assuntos
Anticorpos Monoclonais/genética , Anticorpos Antivirais/genética , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Integrase de HIV/genética , Lentivirus/genética , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Expressão Gênica , Ordem dos Genes , Células HEK293 , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vírus da Influenza A/imunologia , Camundongos , Infecções por Orthomyxoviridae/imunologia
18.
Cell Rep ; 33(5): 108345, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33147460

RESUMO

Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner. As the master regulators of innate immunity, the IRFs control the kinetics and maintenance of the IRG response and play essential roles in response to influenza A virus (IAV), herpes simplex virus 1 (HSV-1), Melaka virus/Pteropine orthoreovirus 3 Melaka (PRV3M), and Middle East respiratory syndrome-related coronavirus (MERS-CoV) infection. With its differential expression in bats compared to that in humans, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.


Assuntos
Quirópteros/imunologia , Regulação da Expressão Gênica/imunologia , Fator Regulador 1 de Interferon/imunologia , Fator Regulador 7 de Interferon/imunologia , Viroses/imunologia , Animais , Herpesvirus Humano 1/imunologia , Vírus da Influenza A/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Orthoreovirus/imunologia
19.
Bol Med Hosp Infant Mex ; 77(5): 262-273, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064680

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Alphainfluenzavirus are RNA viruses that cause coronavirus disease-19 and influenza, respectively. Both viruses infect the respiratory tract, show similar symptoms, and use surface proteins to infect the host. Influenza requires hemagglutinin and neuraminidase to infect, whereas SARS-CoV-2 uses protein S. Both viruses depend on a viral RNA polymerase to express their proteins, but only SARS-CoV-2 has a proofreading mechanism, which results in a low mutation rate compared to influenza. E1KC4 and camostat mesylate are potential inhibitors of SARS-CoV-2 S protein, achieving an effect similar to oseltamivir. Due to the SARS-CoV-2 low mutation rate, nucleoside analogs have been developed (such as EIDD-2801), which insert lethal mutations in the viral RNA. Furthermore, the SARS-CoV-2 low mutation rate suggests that a vaccine, as well as the immunity developed in recovered patients, could provide long-lasting protection compared to vaccines against influenza, which are rendered obsolete as the virus mutates.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Influenza Humana/virologia , Pneumonia Viral/virologia , Animais , Antivirais/administração & dosagem , Antivirais/farmacologia , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Vírus da Influenza A/imunologia , Vírus da Influenza A/isolamento & purificação , Influenza Humana/imunologia , Mutação , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Vacinas Virais
20.
Biomed Environ Sci ; 33(9): 670-679, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-33106212

RESUMO

Objective: In China, 24 cases of human infection with highly pathogenic avian influenza (HPAI) H5N6 virus have been confirmed since the first confirmed case in 2014. Therefore, we developed and assessed two H5N6 candidate vaccine viruses (CVVs). Methods: In accordance with the World Health Organization (WHO) recommendations, we constructed two reassortant viruses using reverse genetics (RG) technology to match the two different epidemic H5N6 viruses. We performed complete genome sequencing to determine the genetic stability. We assessed the growth ability of the studied viruses in MDCK cells and conducted a hemagglutination inhibition assay to analyze their antigenicity. Pathogenicity attenuation was also evaluated in vitro and in vivo. Results: The results showed that no mutations occurred in hemagglutinin or neuraminidase, and both CVVs retained their original antigenicity. The replication capacity of the two CVVs reached a level similar to that of A/Puerto Rico/8/34 in MDCK cells. The two CVVs showed low pathogenicity in vitro and in vivo, which are in line with the WHO requirements for CVVs. Conclusion: We obtained two genetically stable CVVs of HPAI H5N6 with high growth characteristics, which may aid in our preparedness for a potential H5N6 pandemic.


Assuntos
Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Influenza Aviária/epidemiologia , Influenza Aviária/prevenção & controle , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Animais , Aves , China , Humanos
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