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1.
J Clin Invest ; 131(5)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33529172

RESUMO

BACKGROUNDTo understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 encoding influenza virus H5 HA (Ad4-H5-Vtn) administered as an oral capsule or via tonsillar swab or nasal spray.METHODSViral shedding from the nose, mouth, and rectum was measured by PCR and culturing. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition, microneutralization, and HA inhibition assays.RESULTSAd4-H5-Vtn DNA was shed from most upper respiratory tract-immunized (URT-immunized) volunteers for 2 to 4 weeks, but cultured from only 60% of participants, with a median duration of 1 day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood as well as increases in IgG and IgA in nasal, cervical, and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAbs) against H5 that remained stable out to week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AEs) were mild, and peak NAb titers were associated with overall AE frequency and duration. Serum NAb titers could be boosted to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine.CONCLUSIONReplicating Ad4 delivered to the URT caused prolonged exposure to antigen, drove durable systemic and mucosal immunity, and proved to be a promising platform for the induction of immunity against viral surface glycoprotein targets.TRIAL REGISTRATIONClinicalTrials.gov NCT01443936 and NCT01806909.FUNDINGIntramural and Extramural Research Programs of the NIAID, NIH (U19 AI109946) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS), NIAID, NIH (contract HHSN272201400008C).


Assuntos
Adenovírus Humanos/genética , Vetores Genéticos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Adenovírus Humanos/imunologia , Adenovírus Humanos/fisiologia , Administração Oral , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos Virais/genética , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Imunidade Celular , Imunidade Humoral , Imunidade nas Mucosas , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/genética , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Masculino , Sprays Nasais , Tonsila Palatina , Replicação Viral , Eliminação de Partículas Virais , Adulto Jovem
2.
Cell Host Microbe ; 29(2): 148-149, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33571439

RESUMO

Much of our understanding of the way mucosal surfaces achieve a harmonious balance with their resident commensal microbiota derives from analysis of this interplay in the gut. Koren et al. (2021) interrogate the dynamics of this relationship in the mouth during early life and find that highly tissue-specific responses facilitate maturation.


Assuntos
Imunidade nas Mucosas , Microbiota , Epitélio , Boca , Mucosa Bucal
3.
Mucosal Immunol ; 14(2): 296-304, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33500564

RESUMO

Bacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host's defense against viral respiratory infections. The gut microbiota's composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota's composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung-gut axis in coronavirus disease 2019.


Assuntos
Microbioma Gastrointestinal , Pulmão/imunologia , Animais , Dieta , Fibras na Dieta/metabolismo , Disbiose/imunologia , Disbiose/microbiologia , Humanos , Imunidade nas Mucosas , Influenza Humana/imunologia , Probióticos , Vírus Sinciciais Respiratórios , Infecções Respiratórias
4.
Science ; 371(6526)2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33446526

RESUMO

Human monogenic disorders have revealed the critical contribution of type 17 responses in mucosal fungal surveillance. We unexpectedly found that in certain settings, enhanced type 1 immunity rather than defective type 17 responses can promote mucosal fungal infection susceptibility. Notably, in mice and humans with AIRE deficiency, an autoimmune disease characterized by selective susceptibility to mucosal but not systemic fungal infection, mucosal type 17 responses are intact while type 1 responses are exacerbated. These responses promote aberrant interferon-γ (IFN-γ)- and signal transducer and activator of transcription 1 (STAT1)-dependent epithelial barrier defects as well as mucosal fungal infection susceptibility. Concordantly, genetic and pharmacologic inhibition of IFN-γ or Janus kinase (JAK)-STAT signaling ameliorates mucosal fungal disease. Thus, we identify aberrant T cell-dependent, type 1 mucosal inflammation as a critical tissue-specific pathogenic mechanism that promotes mucosal fungal infection susceptibility in mice and humans.


Assuntos
Candida albicans/imunologia , Candidíase Mucocutânea Crônica/genética , Candidíase Mucocutânea Crônica/imunologia , Imunidade nas Mucosas/imunologia , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/imunologia , Adolescente , Adulto , Idoso , Animais , Modelos Animais de Doenças , Feminino , Humanos , Imunidade nas Mucosas/genética , Vigilância Imunológica/genética , Vigilância Imunológica/imunologia , Interferon gama/genética , Interleucinas/genética , Janus Quinases/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Receptores de Interleucina-17/genética , Fator de Transcrição STAT1/genética , Linfócitos T/imunologia , Adulto Jovem
5.
Arch Virol ; 166(2): 545-557, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33409549

RESUMO

The use of gamma-irradiated influenza A virus (γ-Flu), retains most of the viral structural antigens, represent a promising option for vaccine development. However, despite the high effectiveness of γ-Flu vaccines, the need to incorporate an adjuvant to improve vaccine-mediated protection seems inevitable. Here, we examined the protective efficacy of an intranasal gamma-irradiated HIN1 vaccine co-administered with a plasmid encoding mouse interleukin-28B (mIL-28B) as a novel adjuvant in BALB/c mice. Animals were immunized intranasally three times at one-week intervals with γ-Flu, alone or in combination with the mIL-28B adjuvant, followed by viral challenge with a high lethal dose (10 LD50) of A/PR/8/34 (H1N1) influenza virus. Virus-specific antibody, cellular and mucosal responses, and the balance of cytokines in the spleen IFN-γ, IL-12, and IL-4) and in lung homogenates (IL-6 and IL-10) were measured by ELISA. The lymphoproliferative activity of restimulated spleen cells was also determined by MTT assay. Furthermore, virus production in the lungs of infected mice was estimated using the Madin-Darby canine kidney (MDCK)/hemagglutination assay (HA). Our data showed that intranasal immunization with adjuvanted γ-Flu vaccine efficiently promoted humoral, cellular, and mucosal immune responses and efficiently decreased lung virus titers, all of which are associated with protection against challenge. This combination also reduced IL-6 and IL-10 levels in lung homogenates. The results suggest that IL-28B can enhance the ability of the vaccine to elicit virus-specific immune responses and could potentially be used as an effective adjuvant.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Citocinas/imunologia , Imunidade Celular/imunologia , Imunidade nas Mucosas/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Infecções por Orthomyxoviridae/imunologia , Administração Intranasal/métodos , Animais , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Cães , Feminino , Imunização/métodos , Vacinas contra Influenza/imunologia , Pulmão/imunologia , Pulmão/virologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/virologia , Vacinação/métodos
7.
Methods Mol Biol ; 2182: 153-160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32894494

RESUMO

A simple procedure for obtaining outer membrane vesicles from Salmonella enterica and the use of hydrogels as vaccine delivery system is described. A heat treatment in saline solution of whole bacteria rendered the release of outer membrane vesicles containing relevant antigenic components. The immunogenicity of these antigens when administered by the intranasal route may be improved after embedment into hydrogels to increase residence half-time and thus activate the mucosal immune system.


Assuntos
Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/imunologia , Hidrogéis/química , Vacinas/química , Vacinas/imunologia , Administração Intranasal/métodos , Antígenos de Bactérias/química , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Imunidade nas Mucosas/imunologia , Imunogenicidade da Vacina/imunologia , Salmonella enterica/imunologia
8.
Methods Mol Biol ; 2225: 39-61, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108656

RESUMO

Vaccines are the most effective means to prevent infectious diseases, especially for viral infection. The key to an excellent antiviral vaccine is the ability to induce long-term protective immunity against a specific virus. Bacterial vaccine vectors have been used to impart protection against self, as well as heterologous antigens. One significant benefit of using live bacterial vaccine vectors is their ability to invade and colonize deep effector lymphoid tissues after mucosal delivery. The bacterium Salmonella is considered the best at this deep colonization. This is critically essential for inducing protective immunity. This chapter describes the methodology for developing genetically modified self-destructing Salmonella (GMS) vaccine delivery systems targeting influenza infection. Specifically, the methods covered include the procedures for the development of GMSs for protective antigen delivery to induce cellular immune responses and DNA vaccine delivery to induce systemic immunity against the influenza virus. These self-destructing GMS could be modified to provide effective biological containment for genetically engineered bacteria used for a diversity of purposes in addition to vaccines.


Assuntos
Engenharia Genética/métodos , Imunização/métodos , Vacinas contra Influenza/genética , Influenza Humana/prevenção & controle , Salmonella typhimurium/genética , Vacinas de DNA/genética , Animais , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Antígenos Virais/genética , Antígenos Virais/imunologia , Feminino , Genes Letais , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Influenza Humana/imunologia , Influenza Humana/virologia , Camundongos , Camundongos Endogâmicos BALB C , Nucleoproteínas/genética , Nucleoproteínas/imunologia , Organismos Geneticamente Modificados , Plasmídeos/química , Plasmídeos/metabolismo , Salmonella typhimurium/imunologia , Transgenes
9.
Cell Host Microbe ; 29(2): 236-249.e6, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33357418

RESUMO

To develop a vaccine candidate against coronavirus disease 2019 (COVID-19), we generated a lentiviral vector (LV) eliciting neutralizing antibodies against the Spike glycoprotein of SARS-CoV-2. Systemic vaccination by this vector in mice, in which the expression of the SARS-CoV-2 receptor hACE2 has been induced by transduction of respiratory tract cells by an adenoviral vector, confers only partial protection despite high levels of serum neutralizing activity. However, eliciting an immune response in the respiratory tract through an intranasal boost results in a >3 log10 decrease in the lung viral loads and reduces local inflammation. Moreover, both integrative and non-integrative LV platforms display strong vaccine efficacy and inhibit lung deleterious injury in golden hamsters, which are naturally permissive to SARS-CoV-2 replication and closely mirror human COVID-19 physiopathology. Our results provide evidence of marked prophylactic effects of LV-based vaccination against SARS-CoV-2 and designate intranasal immunization as a powerful approach against COVID-19.


Assuntos
Administração Intranasal/métodos , /imunologia , /imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Cricetinae , Feminino , Vetores Genéticos , Imunidade nas Mucosas , Imunização Secundária , Imunoglobulina A/imunologia , Lentivirus/genética , Lentivirus/imunologia , Masculino , Camundongos , Modelos Animais , Sistema Respiratório/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Carga Viral
10.
Mol Immunol ; 130: 142-147, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33358570

RESUMO

MAIT cells are innate-like T cells that are enriched in mucosal sites and tissues including adipose tissue and liver. They play an important role in immunity against microbial pathogens. Recently, it has been reported that MAIT cells could also be important in metabolic diseases and can be involved in setting up and maintaining chronic inflammation. In this review, we give an overview of recent advances in understanding MAIT cells role in the ethology of this diseases.


Assuntos
Doenças Metabólicas/etiologia , Células T Invariáveis Associadas à Mucosa/fisiologia , Tecido Adiposo/imunologia , Tecido Adiposo/fisiologia , Animais , Humanos , Imunidade nas Mucosas/fisiologia , Fígado/imunologia , Fígado/fisiologia , Doenças Metabólicas/imunologia , Doenças Metabólicas/patologia
11.
Mol Immunol ; 130: 64-68, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33360378

RESUMO

The monomorphic MHC-class I-like molecule, MR1, presents small metabolites to T cells. MR1 is the restriction element for microbe-reactive mucosal-associated invariant T (MAIT) cells. MAIT cells have limited TCR usage, including a semi-invariant TCR alpha chain and express high levels of CD161 and CD26. In addition to microbial lumazine metabolites, recent studies have demonstrated that MR1 is able to capture a variety of diverse chemical entities including folate-derivatives, a number of drug-like and other synthetic small molecules, and as yet undefined compounds of self-origin. This capacity of MR1 to bind distinct ligands likely accounts for the recent identification of additional, non-canonical, subsets of MR1-restricted T (MR1T) cells. These subsets can be defined based on their ability to recognize diverse microbes as well as their reactivity to non-microbial cell-endogenous ligands, including tumor-associated antigens. Herein, we will discuss our current understanding of MR1T cell diversity in terms of TCR usage, ligand recognition and functional attributes.


Assuntos
Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , Células T Invariáveis Associadas à Mucosa/metabolismo , Receptores de Antígenos de Linfócitos T/imunologia , Especificidade do Receptor de Antígeno de Linfócitos T/fisiologia , Subpopulações de Linfócitos T/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imunidade nas Mucosas/imunologia , Antígenos de Histocompatibilidade Menor/imunologia , Células T Invariáveis Associadas à Mucosa/imunologia , Receptores de Antígenos de Linfócitos T/fisiologia , Receptores de Antígenos de Linfócitos T alfa-beta
12.
Ecotoxicol Environ Saf ; 207: 111287, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32931967

RESUMO

Coming along with high water reuse in sustainable and intensive recirculating aquaculture systems (RASs), the waste products of fish in rearing water is continuously accumulated. Nitrate, the final product of biological nitrification processes, which may cause aquatic toxicity to fish in different degrees when exposed for a long time. Therefore, the present study was conducted to evaluate the impact of chronic nitrate exposure on intestinal morphology, immune status, barrier function, and microbiota of juvenile turbot. For that, groups of juvenile turbot were exposed to 0 (control check, CK), 50 (low nitrate, L), 200 (medium nitrate, M), and 400 (high nitrate, H) mg L-1 nitrate-N in small-sized recirculating aquaculture systems. After the 60-day experiment period, we found that exposure to a high concentration of nitrate-N caused obvious pathological damages to the intestine; for instance, atrophy of intestinal microvilli and necrosis in the lamina propria. Quantitative real-time PCR analysis revealed a significant downregulation of the barrier forming tight junction genes like occludin, claudin-like etc. under H treatment (P < 0.05). Intestinal MUC-2 expression also decreased significantly in the nitrate treatment groups compared to that in the control (P < 0.05). Additionally, the expression of HSP70 and HSP90 heat-shock proteins, toll-like receptor-3 (TLR-3), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) significantly increased (P < 0.05), whereas that of transforming growth factor-ß (TGF-ß), lysozyme (LYS), and insulin-like growth factor-I (IGF-I) significantly decreased with H treatment (P < 0.05). The results also revealed that intestinal microbial community was changed following nitrate exposure and could alter the α-diversity and ß-diversity. Specifically, the proportion of intrinsic flora decreased, whereas that of the potential pathogens significantly increased with M and H treatments (P < 0.05). In conclusion, chronic nitrate exposure could weaken the barrier function and disturb the composition of intestinal microbiota in marine teleosts, thereby harming their health condition.


Assuntos
Linguados/crescimento & desenvolvimento , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Nitratos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , DNA Bacteriano/genética , Relação Dose-Resposta a Droga , Linguados/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Intestinos/microbiologia
13.
Front Immunol ; 11: 611337, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329607

RESUMO

The mucosal immune system is the largest component of the entire immune system, having evolved to provide protection at the main sites of infectious threat: the mucosae. As SARS-CoV-2 initially infects the upper respiratory tract, its first interactions with the immune system must occur predominantly at the respiratory mucosal surfaces, during both inductive and effector phases of the response. However, almost all studies of the immune response in COVID-19 have focused exclusively on serum antibodies and systemic cell-mediated immunity including innate responses. This article proposes that there is a significant role for mucosal immunity and for secretory as well as circulating IgA antibodies in COVID-19, and that it is important to elucidate this in order to comprehend especially the asymptomatic and mild states of the infection, which appear to account for the majority of cases. Moreover, it is possible that mucosal immunity can be exploited for beneficial diagnostic, therapeutic, or prophylactic purposes.


Assuntos
Anticorpos Antivirais/imunologia , Imunidade nas Mucosas , Imunoglobulina A/imunologia , /imunologia , /diagnóstico , /patologia , Humanos
14.
PLoS One ; 15(12): e0240773, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33378402

RESUMO

Infectious diseases are a threat to elderly individuals, whose immune systems weaken with age. Among the various infectious diseases, Clostridium difficile infection is associated with a high rate of mortality in elderly individuals and is a serious health problem worldwide, owing to the increasing infection rates. Probiotic use has been proposed as an effective countermeasure for C. difficile infection. The aim of this study was to evaluate the effects of heat-killed Enterococcus faecalis T-110 on intestinal immunity, intestinal flora, and intestinal infections, especially C. difficile infections, in naturally ageing animals, for extrapolating the results to elderly human subjects. Twenty female hamsters were randomly distributed into two groups. Group 1 was fed a basal diet and group 2 was fed a basal diet supplemented with heat-killed E. faecalis for 7 days. Heat-killed E. faecalis T-110 improved the gut immunity and microflora, especially Clostridium perfringens and C. difficile, in naturally aged hamsters. Therefore, heat-killed E. faecalis T-110 use may be a countermeasure against age-related immune dysfunction and intestinal infections, especially C. difficile infection, in elderly humans. However, further investigation in this regard is needed in humans.


Assuntos
Envelhecimento/imunologia , Infecções por Clostridium/prevenção & controle , Diarreia/prevenção & controle , Enterococcus faecalis/imunologia , Probióticos/administração & dosagem , Fatores Etários , Idoso , Animais , /isolamento & purificação , Infecções por Clostridium/imunologia , Infecções por Clostridium/microbiologia , Clostridium perfringens/imunologia , Clostridium perfringens/isolamento & purificação , Cricetinae , Diarreia/imunologia , Diarreia/microbiologia , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/imunologia , Temperatura Alta , Humanos , Tolerância Imunológica/fisiologia , Imunidade nas Mucosas , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia
15.
PLoS One ; 15(10): e0239987, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031424

RESUMO

The microbial communities colonize the mucosal immune inductive sites could be captured by hosts, which could initiate the mucosal immune responses. The aggregated lymphoid nodule area (ALNA) and the ileal Payer's patches (PPs) in Bactrian camels are both the mucosal immune inductive sites of the gastrointestinal tract. Here, the bacteria community associated with the ALNA and ileal PPs were analyzed using of 16S rDNA-Illumina Miseq sequencing. The mutual dominant bacterial phyla at the two sites were the Bacteroidetes, Firmicutes, Verrucomicrobia and Proteobacteria, and the mutual dominant genus in both sits was Prevotella. The abundances of the Fibrobacter, Campylobacter and RFP12 were all higher in ALNA than in ileal PPs. While, the abundances of the 5-7N15, Clostridium, and Escherichia were all higher in ileal PPs than in ALNA. The results suggested that the host's intestinal microenvironment is selective for the symbiotic bacteria colonizing the corresponding sites, on the contrary, the symbiotic bacteria could impact on the physiological functions of this local site. In ALNA and ileal PPs of Bactrian camel, the bacteria which colonized different immune inductive sites have the potential to stimulate different immune responses, which is the result of the mutual selection and adaptation between microbial communities and their host.


Assuntos
Trato Gastrointestinal/microbiologia , Imunidade nas Mucosas , Tecido Linfoide/microbiologia , Microbiota , Animais , Bactérias/genética , Bactérias/isolamento & purificação , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Biodiversidade , Camelus , Fibrobacter/genética , Fibrobacter/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Tecido Linfoide/imunologia , Análise de Componente Principal , RNA Ribossômico 16S/química , RNA Ribossômico 16S/metabolismo , Simbiose
18.
Viruses ; 12(9)2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32961897

RESUMO

Some coronaviruses are zoonotic viruses of human and veterinary medical importance. The novel coronavirus, severe acute respiratory symptoms coronavirus 2 (SARS-CoV-2), associated with the current global pandemic, is characterized by pneumonia, lymphopenia, and a cytokine storm in humans that has caused catastrophic impacts on public health worldwide. Coronaviruses are known for their ability to evade innate immune surveillance exerted by the host during the early phase of infection. It is important to comprehensively investigate the interaction between highly pathogenic coronaviruses and their hosts. In this review, we summarize the existing knowledge about coronaviruses with a focus on antiviral immune responses in the respiratory and intestinal tracts to infection with severe coronaviruses that have caused epidemic diseases in humans and domestic animals. We emphasize, in particular, the strategies used by these coronaviruses to circumvent host immune surveillance, mainly including the hijack of antigen-presenting cells, shielding RNA intermediates in replication organelles, 2'-O-methylation modification for the evasion of RNA sensors, and blocking of interferon signaling cascades. We also provide information about the potential development of coronavirus vaccines and antiviral drugs.


Assuntos
Antivirais/imunologia , Infecções por Coronavirus/virologia , Coronavirus/imunologia , Evasão da Resposta Imune , Pneumonia Viral/virologia , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Coronavirus/classificação , Coronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Imunidade Inata , Imunidade nas Mucosas , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Transdução de Sinais , Tropismo Viral
19.
Nature ; 586(7830): 516-527, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32967006

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 in China and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. To mitigate the effects of the virus on public health, the economy and society, a vaccine is urgently needed. Here I review the development of vaccines against SARS-CoV-2. Development was initiated when the genetic sequence of the virus became available in early January 2020, and has moved at an unprecedented speed: a phase I trial started in March 2020 and there are currently more than 180 vaccines at various stages of development. Data from phase I and phase II trials are already available for several vaccine candidates, and many have moved into phase III trials. The data available so far suggest that effective and safe vaccines might become available within months, rather than years.


Assuntos
Infecções por Coronavirus , Desenvolvimento de Medicamentos , Pandemias , Pneumonia Viral , Vacinas Virais , Animais , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Indústria Farmacêutica , Humanos , Imunidade nas Mucosas , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia , Vacinas Virais/provisão & distribução
20.
Nat Commun ; 11(1): 4475, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901029

RESUMO

Tissue resident memory CD8+ T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-mediated colonization resistance, and favor intestinal expansion to high densities of an orally-delivered Listeria monocytogenes strain carrying an antigen of choice. By augmenting the local chemotactic gradient as well as the antigenic load, this procedure generates a highly expanded pool of functional, antigen-specific intestinal Trm, ultimately enhancing protection against infectious re-challenge in mice. We propose that TMDI is a useful model to dissect the requirements for optimal Trm responses in the intestine, and also a potential platform to devise novel mucosal vaccination approaches.


Assuntos
Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas , Administração Oral , Animais , Antígenos/administração & dosagem , Linfócitos T CD8-Positivos/imunologia , Quimiotaxia/imunologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Memória Imunológica , Listeria monocytogenes/crescimento & desenvolvimento , Listeria monocytogenes/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina/administração & dosagem , Estreptomicina/administração & dosagem
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