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1.
Immunity ; 54(2): 340-354.e6, 2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33567252

RESUMEN

Cellular and humoral immunity to SARS-CoV-2 is critical to control primary infection and correlates with severity of disease. The role of SARS-CoV-2-specific T cell immunity, its relationship to antibodies, and pre-existing immunity against endemic coronaviruses (huCoV), which has been hypothesized to be protective, were investigated in 82 healthy donors (HDs), 204 recovered (RCs), and 92 active COVID-19 patients (ACs). ACs had high amounts of anti-SARS-CoV-2 nucleocapsid and spike IgG but lymphopenia and overall reduced antiviral T cell responses due to the inflammatory milieu, expression of inhibitory molecules (PD-1, Tim-3) as well as effector caspase-3, -7, and -8 activity in T cells. SARS-CoV-2-specific T cell immunity conferred by polyfunctional, mainly interferon-γ-secreting CD4+ T cells remained stable throughout convalescence, whereas humoral responses declined. Immune responses toward huCoV in RCs with mild disease and strong cellular SARS-CoV-2 T cell reactivity imply a protective role of pre-existing immunity against huCoV.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Inmunidad Celular/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Femenino , Humanos , Inmunidad Humoral/inmunología , Masculino , Persona de Mediana Edad , Adulto Joven
2.
Arch Virol ; 166(2): 545-557, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33409549

RESUMEN

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.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Citocinas/inmunología , Inmunidad Celular/inmunología , Inmunidad Mucosa/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Infecciones por Orthomyxoviridae/inmunología , Administración Intranasal/métodos , Animales , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Perros , Femenino , Inmunización/métodos , Vacunas contra la Influenza/inmunología , Pulmón/inmunología , Pulmón/virología , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/virología , Vacunación/métodos
3.
Cell Syst ; 12(1): 102-107.e4, 2021 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-33321075

RESUMEN

Subunit vaccines induce immunity to a pathogen by presenting a component of the pathogen and thus inherently limit the representation of pathogen peptides for cellular immunity-based memory. We find that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit peptides may not be robustly displayed by the major histocompatibility complex (MHC) molecules in certain individuals. We introduce an augmentation strategy for subunit vaccines that adds a small number of SARS-CoV-2 peptides to a vaccine to improve the population coverage of pathogen peptide display. Our population coverage estimates integrate clinical data on peptide immunogenicity in convalescent COVID-19 patients and machine learning predictions. We evaluate the population coverage of 9 different subunits of SARS-CoV-2, including 5 functional domains and 4 full proteins, and augment each of them to fill a predicted coverage gap.


Asunto(s)
/inmunología , /prevención & control , Inmunidad Celular/inmunología , Aprendizaje Automático , Vacunas de Subunidad/inmunología , /administración & dosificación , Predicción , Humanos , Inmunidad Celular/efectos de los fármacos , Vacunas de Subunidad/administración & dosificación
4.
Nat Microbiol ; 6(1): 73-86, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33340034

RESUMEN

Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.


Asunto(s)
/veterinaria , Callithrix/inmunología , Pulmón/inmunología , Macaca mulatta/inmunología , Enfermedades de los Monos/virología , Papio/inmunología , /inmunología , Inmunidad Adaptativa , Animales , Anticuerpos Antivirales/inmunología , Lavado Broncoalveolar , Líquido del Lavado Bronquioalveolar , /inmunología , Femenino , Humanos , Inmunidad Celular/inmunología , Inmunoglobulina G/inmunología , Inflamación/patología , Pulmón/virología , Masculino , Enfermedades de los Monos/inmunología , Células Mieloides/inmunología , Carga Viral , Esparcimiento de Virus
5.
Front Immunol ; 11: 571481, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33362759

RESUMEN

In December 2019, an outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China resulted in the current COVID-19 global pandemic. The human immune system has not previously encountered this virus, raising the important question as to whether or not protective immunity is generated by infection. Growing evidence suggests that protective immunity can indeed be acquired post-infection-although a handful of reinfection cases have been reported. However, it is still unknown whether the immune response to SARS-CoV-2 leads to some degree of long-lasting protection against the disease or the infection. This review draws insights from previous knowledge regarding the nature and longevity of immunity to the related virus, SARS-CoV, to fill the gaps in our understanding of the immune response to SARS-CoV-2. Deciphering the immunological characteristics that give rise to protective immunity against SARS-CoV-2 is critical to guiding vaccine development and also predicting the course of the pandemic. Here we discuss the recent evidence that characterises the adaptive immune response against SARS-CoV-2 and its potential implications for the generation of memory responses and long-term protection.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Inmunidad Celular/inmunología , Memoria Inmunológica/inmunología , /inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , /prevención & control , /inmunología , Humanos
6.
Neuroimmunomodulation ; 27(2): 80-86, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33341814

RESUMEN

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide. The pathophysiology of this virus is not very clearly known, thus, enormous efforts are being made by the scientific community to delineate its evading mechanism. In this review, we have summarized the hyperinflammation and humoral and cell-mediated immune response generated in human body after infection with the SARS-CoV-2 virus. The inflammatory response generated after infection by increased proinflammatory cytokines and chemokines, and complement proteins activation may likely contribute to disease severity. We also discussed the other factors that may affect immunity and could be important comorbidities in the disease severity and outcome.


Asunto(s)
/inmunología , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Inmunidad Innata/inmunología , Inflamación/inmunología , Inmunidad Adaptativa/inmunología , Alarminas/inmunología , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Activación de Complemento/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Humanos , Células Asesinas Naturales/inmunología , Índice de Severidad de la Enfermedad
7.
J Immunol Res ; 2020: 8375096, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33354578

RESUMEN

Recently, the novel coronavirus epidemic occurred in China and spread worldwide to become a global pandemic. COVID-19 is a fatal viral infection causing death, particularly in aged individuals, due to impaired immunity. To date, no intervention is available to prevent COVID-19 and its manifestations. Physical exercise training generally has health benefits, and it assists in the prevention of several chronic diseases. Therefore, this review is aimed at exploring the role of physical exercise training in the face of COVID-19 in older adults and elderly individuals. From this point of view, this review suggests that physical exercise training plays a key role in promoting immune system regulation, delaying immunity dysfunction, reducing circulatory inflammation markers, and preventing sarcopenia and thus could prevent the risk of acquiring COVID-19 infection and reduce the complications of recommended self-isolation in older adults and elderly individuals. Additionally, immunity biomarkers were optimistically demonstrated in older adults following physical exercise training, thereby reducing mortality and morbidity rates. Finally, in accordance with recommendations to stay home and perform self-isolation to prevent the spread of COVID-19, all populations are strongly recommended to practice regular home exercise training at home to promote immune system functioning.


Asunto(s)
Ejercicio Físico/fisiología , Ejercicio Físico/psicología , Anciano , Anciano de 80 o más Años , Anciano Frágil/psicología , Humanos , Inmunidad Celular/inmunología , Aislamiento de Pacientes , Carencia Psicosocial , Sarcopenia/prevención & control
8.
Int J Nanomedicine ; 15: 10321-10330, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33364759

RESUMEN

Background: Vaccination provides a viable alternative to antibiotics for the treatment of drug-resistant bacterial infection. Bacterial protoplasts have gained much attention for a new generation vaccine due to depleting toxic outer wall components. Purpose: The objective of this study was to reveal the effects of bacterial protoplast-derived nanovesicles (PDNVs) size on antibacterial immunity. Methods: Herein, we prepared bacterial PDNVs with different sizes by removing the cell wall of Staphylococcus aureus (S. aureus) to generate multi-antigen nanovaccines. Furthermore, we investigated the ability of PDNVs in different sizes to activate dendritic cells (DCs) and trigger humoral and cellular immune responses in vivo. Results: We obtained particles of ∼200 nm, 400 nm, and 700 nm diameters and found that all the PDNVs readily induce efficient maturation of DCs in the draining lymph nodes of the vaccinated mice. Dramatically, the activation of DCs was increased with decreasing particle sizes. In addition, vaccination with PDNVs generated elevated expression levels of specific antibody and the production of INF-γ, especially the smaller ones, indicating the capability of inducing strong humoral immunity and Th1 biased cell responses against the source bacteria. Conclusion: These observed results provide evidence for size-dependent orchestration of immune responses of PDNVs and help to rationally design and develop effective antibacterial vaccines.


Asunto(s)
Vacunas Bacterianas/química , Vacunas Bacterianas/inmunología , Protoplastos/química , Staphylococcus aureus/citología , Staphylococcus aureus/inmunología , Animales , Células Dendríticas/inmunología , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Ratones , Nanoestructuras/química
9.
Lancet Oncol ; 21(9): e419-e430, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32888471

RESUMEN

Notable advances have been achieved in the treatment of cancer since the advent of immunotherapy, and immune checkpoint inhibitors have shown clinical benefit across a wide variety of tumour types. Nevertheless, most patients still progress on these treatments, highlighting the importance of unravelling the underlying mechanisms of primary resistance to immunotherapy. A well described biomarker of non-responsiveness to immune checkpoint inhibitors is the absence or low presence of lymphocytes in the tumour microenvironment, so-called cold tumours. There are five mechanisms of action that have the potential to turn cold tumours into so-called hot and inflamed tumours, hence increasing the tumour's responsiveness to immunotherapy-increasing local inflammation, neutralising immunosuppression at the tumour site, modifying the tumour vasculature, targeting the tumour cells themselves, or increasing the frequency of tumour-specific T cells. In this Review, we discuss preclinical data that serves as the basis for ongoing immunotherapy clinical trials for the treatment of non-immunoreactive tumours, as well as reviewing clinical and translational data where available. We explain how improving our understanding of the underlying mechanisms of primary resistance to immunotherapy will help elucidate an increasingly granular view of the tumour microenvironment cellular composition, functional status, and cellular localisation, with the goal of further therapy refinement.


Asunto(s)
Resistencia a Antineoplásicos/inmunología , Inmunoterapia/efectos adversos , Inflamación/terapia , Neoplasias/terapia , Microambiente Tumoral/efectos de los fármacos , Antineoplásicos Inmunológicos/inmunología , Antineoplásicos Inmunológicos/uso terapéutico , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/antagonistas & inhibidores , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/inmunología , Ensayos Clínicos como Asunto , Humanos , Inmunidad Celular/inmunología , Inflamación/inmunología , Inflamación/patología , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Neoplasias/inmunología , Neoplasias/patología , Microambiente Tumoral/inmunología
10.
Hum Immunol ; 81(10-11): 588-595, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32888767

RESUMEN

Coronavirus Disease 2019 (COVID-19) is a dangerous global threat that has no clinically approved treatment yet. Bioinformatics represent an outstanding approach to reveal key immunogenic regions in viral proteins. Here, five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural proteins (NSPs) (NSP7, NSP8, NSP9, NSP12, and NSP13) were screened to identify potential human leukocyte antigen (HLA) binding peptides. These peptides showed robust viral antigenicity, immunogenicity, and a marked interaction with HLA alleles. Interestingly, several peptides showed affinity by HLA class I (HLA-I) alleles that commonly activates to natural killer (NK) cells. Notably, HLA biding peptides are conserved among SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). Interestingly, HLA-I and HLA class II (HLA-II) binding peptides induced humoral and cell-mediated responses after in silico vaccination. These results may open further in vitro and in vivo investigations to develop novel therapeutic strategies against coronaviral infections.


Asunto(s)
Betacoronavirus/inmunología , Secuencia Conservada/inmunología , Infecciones por Coronavirus/inmunología , Antígenos HLA/inmunología , Neumonía Viral/inmunología , Proteínas no Estructurales Virales/inmunología , Secuencia de Aminoácidos , Betacoronavirus/genética , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Antígenos HLA/metabolismo , Humanos , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Simulación del Acoplamiento Molecular , Pandemias , Neumonía Viral/sangre , Neumonía Viral/terapia , Neumonía Viral/virología , Virus del SRAS/genética , Virus del SRAS/inmunología , Vacunas de Subunidad/inmunología , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Vacunas Virales/inmunología
11.
Anticancer Res ; 40(10): 5355-5359, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32988854

RESUMEN

BACKGROUND/AIM: Recent studies indicate that chimeric antigen receptor (CAR)-T-cells seem to be superior to CAR modified NK-92 cells. One, at least partial, explanation to this discrepancy has been addressed herein, by having NK-92 cells as target cells in cytotoxicity reactions using peripheral blood mononuclear cells. MATERIALS AND METHODS: A time-resolved fluorometric assay (TDA-labeled NK-92 or K562 as target cells) was used for measuring the cytotoxic activity of blood mononuclear cells (PBMC). RESULTS: The cytotoxic capacity of the NK-92 cells was initially demonstrated by their ability to efficiently kill K562 cells. Interestingly, having PBMC as effector cells rendered the very same NK-92 cells sensitive to NK-cell mediated cytolysis. A 1:100 target:effector ratio gave 34.1% lysis compared to 72.2% lysis for K562 cells. Incubating PBMC for longer times (24 up to 48 h) potentiated their NK-activity against NK-92 cells even more, reaching a level close to that obtained with K562 cells. CONCLUSION: This study pinpoints a severe problem that has to be considered in future immune-based cancer therapies with NK-92 as well as CAR-transduced NK-92 cells.


Asunto(s)
Inmunoterapia Adoptiva , Células Asesinas Naturales/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Neoplasias/terapia , Citotoxicidad Inmunológica/efectos de los fármacos , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/inmunología , Interleucina-2/genética , Interleucina-2/inmunología , Células K562 , Neoplasias/inmunología , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología
12.
Sheng Wu Gong Cheng Xue Bao ; 36(7): 1440-1449, 2020 Jul 25.
Artículo en Chino | MEDLINE | ID: mdl-32748602

RESUMEN

Hepatitis B virus core protein can self-assemble into icosahedral symmetrical viral-like particles (VLPs) in vitro, and display exogenous sequences repeatedly and densely on the surface. VLPs also have strong immunogenicity and biological activity. When the nanoparticles enter the body, they quickly induce specific humoral and cellular immune responses to exogenous antigens. In this study, we designed an HBc-VLPs that can be coupled with antigens at specific sites, and developed a set of efficient methods to prepare HBc-VLPs. Through site-specific mutation technology, the 80th amino acid of peptide was changed from Ala to Cys, a specific cross-linking site was inserted into the main immunodominant region of HBc-VLPs, and the prokaryotic expression vector pET28a(+)-hbc was constructed. After expression and purification, high purity HBc(A80C) monomer protein was assembled into HBc-VLPs nanoparticles in Phosphate Buffer. The results of particle size analysis show that the average particle size of nanoparticles was 29.8 nm. Transmission electron microscopy (TEM) showed that HBc-VLPs formed spherical particles with a particle size of about 30 nm, and its morphology was similar to that of natural HBV particles. The influenza virus antigen M2e peptide as model antigen was connected to Cys residue of HBc-VLPs by Sulfo-SMCC, an amino sulfhydryl bifunctional cross-linking agent, and M2e-HBc-VLPs model vaccine was prepared. The integrity of HBc-VLPs structure and the correct cross-linking of M2e were verified by cell fluorescence tracing. Animal immune experiments showed that the vaccine can effectively stimulate the production of antigen-specific IgG antibody in mice, which verified the effectiveness of the vaccine carrier HBc-VLPs. This study lays a foundation for the research of HBc-VLPs as vaccine vector, and help to promote the development of HBc-VLPs vaccine and the application of HBc-VLPs in other fields.


Asunto(s)
Antígenos del Núcleo de la Hepatitis B , Inmunidad Celular , Vacunas de Partículas Similares a Virus , Animales , Antígenos del Núcleo de la Hepatitis B/genética , Antígenos del Núcleo de la Hepatitis B/inmunología , Inmunidad Celular/inmunología , Inmunoglobulina G/sangre , Ratones , Ratones Endogámicos BALB C , Vacunas de Partículas Similares a Virus/genética , Vacunas de Partículas Similares a Virus/inmunología
14.
Anesthesiology ; 133(5): 1060-1076, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32796202

RESUMEN

BACKGROUND: Pulmonary atelectasis is frequent in clinical settings. Yet there is limited mechanistic understanding and substantial clinical and biologic controversy on its consequences. The authors hypothesize that atelectasis produces local transcriptomic changes related to immunity and alveolar-capillary barrier function conducive to lung injury and further exacerbated by systemic inflammation. METHODS: Female sheep underwent unilateral lung atelectasis using a left bronchial blocker and thoracotomy while the right lung was ventilated, with (n = 6) or without (n = 6) systemic lipopolysaccharide infusion. Computed tomography guided samples were harvested for NextGen RNA sequencing from atelectatic and aerated lung regions. The Wald test was used to detect differential gene expression as an absolute fold change greater than 1.5 and adjusted P value (Benjamini-Hochberg) less than 0.05. Functional analysis was performed by gene set enrichment analysis. RESULTS: Lipopolysaccharide-unexposed atelectatic versus aerated regions presented 2,363 differentially expressed genes. Lipopolysaccharide exposure induced 3,767 differentially expressed genes in atelectatic lungs but only 1,197 genes in aerated lungs relative to the corresponding lipopolysaccharide-unexposed tissues. Gene set enrichment for immune response in atelectasis versus aerated tissues yielded negative normalized enrichment scores without lipopolysaccharide (less than -1.23, adjusted P value less than 0.05) but positive scores with lipopolysaccharide (greater than 1.33, adjusted P value less than 0.05). Leukocyte-related processes (e.g., leukocyte migration, activation, and mediated immunity) were enhanced in lipopolysaccharide-exposed atelectasis partly through interferon-stimulated genes. Furthermore, atelectasis was associated with negatively enriched gene sets involving alveolar-capillary barrier function irrespective of lipopolysaccharide (normalized enrichment scores less than -1.35, adjusted P value less than 0.05). Yes-associated protein signaling was dysregulated with lower nuclear distribution in atelectatic versus aerated lung (lipopolysaccharide-unexposed: 10.0 ± 4.2 versus 13.4 ± 4.2 arbitrary units, lipopolysaccharide-exposed: 8.1 ± 2.0 versus 11.3 ± 2.4 arbitrary units, effect of lung aeration, P = 0.003). CONCLUSIONS: Atelectasis dysregulates the local pulmonary transcriptome with negatively enriched immune response and alveolar-capillary barrier function. Systemic lipopolysaccharide converts the transcriptomic immune response into positive enrichment but does not affect local barrier function transcriptomics. Interferon-stimulated genes and Yes-associated protein might be novel candidate targets for atelectasis-associated injury.


Asunto(s)
Inmunidad Celular/genética , Inmunidad Celular/inmunología , Atelectasia Pulmonar/genética , Atelectasia Pulmonar/inmunología , Transcriptoma/genética , Animales , Femenino , Mediciones del Volumen Pulmonar/métodos , Atelectasia Pulmonar/diagnóstico por imagen , Ovinos
16.
Mult Scler ; 26(10): 1261-1264, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32762494

RESUMEN

Approximately 200,000 multiple sclerosis (MS) patients worldwide receive B-cell-depleting immunotherapy with rituximab (anti-CD20), which eliminates the ability to generate an antibody response to new infections. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies might help viral clearance, these patients could be at risk of severe complications if infected. Here, we report on an MS patient who had received rituximab for ~3 years. The patient was examined 5 days before the onset of coronavirus disease 2019 (COVID-19) symptoms and was admitted to the hospital 2 days after. She recovered 14 days after symptom onset despite having a 0% B lymphocyte count and not developing SARS-CoV-2 immunoglobulin G (IgG) antibodies.


Asunto(s)
Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Infecciones por Coronavirus/inmunología , Inmunidad Celular/inmunología , Células Asesinas Naturales/inmunología , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Neumonía Viral/inmunología , Rituximab/uso terapéutico , Betacoronavirus , Relación CD4-CD8 , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/fisiopatología , Progresión de la Enfermedad , Femenino , Humanos , Recuento de Linfocitos , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/complicaciones , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/fisiopatología
17.
Parasitol Res ; 119(9): 2885-2895, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32715344

RESUMEN

Chicken coccidiosis is a protozoan parasitic disease that leads to considerable economic losses in the poultry industry. In this study, we used invasive Lactobacillus plantarum (L.P) expressing the FnBPA protein as a novel bacterial carrier for DNA delivery into epithelial cells to develop a live oral DNA vaccine. A fusion DNA vaccine co-expressing EtMIC2 and chicken IL-18 (chIL-18) was constructed and then delivered to the host by invasive L.P. Its efficacy against Eimeria tenella challenge was evaluated in chickens by examining the relative weight gain rate; caecal lesion score; OPG; anti-coccidial index (ACI); levels of EtMIC2 antibody, FnBPA, IL-4, IL-18, IFN-γ and SIgA; and proliferation ability and percentages of CD4+ and CD8+ splenocytes. The experimental results showed that chickens immunized with invasive L.P carrying the eukaryotic expression vector pValac-EtMIC2 (pValac-EtMIC2/pSIP409-FnBPA) had markedly improved immune protection against challenge compared with that of chickens immunized with non-invasive L.P (pValac-EtMIC2/pSIP409). However, invasive L.P co-expressing EtMIC2 with the chIL-18 vector exhibited the highest protection efficiency against E. tenella. These results indicate that invasive Lactobacillus-expressing FnBPA improved humoural and cellular immunity and enhanced resistance to E. tenella. The DNA vaccine delivered by invasive Lactobacillus provides a new concept and method for the prevention of E. tenella.


Asunto(s)
Antígeno 12E7/metabolismo , Coccidiosis/veterinaria , Eimeria tenella/inmunología , Interleucina-18/metabolismo , Lactobacillus plantarum/metabolismo , Vacunas Antiprotozoos/inmunología , Vacunas de ADN/inmunología , Animales , Ciego/parasitología , Pollos/parasitología , Coccidiosis/parasitología , Eimeria tenella/genética , Inmunidad Celular/inmunología , Inmunoglobulina A Secretora/genética , Lactobacillus plantarum/genética , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/prevención & control , Vacunación/veterinaria , Aumento de Peso
18.
Nat Med ; 26(9): 1428-1434, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32661393

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts1-3, most targeting the viral 'spike' glycoprotein (S). S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)4-6. Eliciting neutralizing antibodies that block S-ACE2 interaction7-9, or indirectly prevent membrane fusion10, constitute an attractive modality for vaccine-elicited protection11. However, although prototypic S-based vaccines show promise in animal models12-14, the immunogenic properties of S in humans are poorly resolved. In this study, we characterized humoral and circulating follicular helper T cell (cTFH) immunity against spike in recovered patients with coronavirus disease 2019 (COVID-19). We found that S-specific antibodies, memory B cells and cTFH are consistently elicited after SARS-CoV-2 infection, demarking robust humoral immunity and positively associated with plasma neutralizing activity. Comparatively low frequencies of B cells or cTFH specific for the receptor binding domain of S were elicited. Notably, the phenotype of S-specific cTFH differentiated subjects with potent neutralizing responses, providing a potential biomarker of potency for S-based vaccines entering the clinic. Overall, although patients who recovered from COVID-19 displayed multiple hallmarks of effective immune recognition of S, the wide spectrum of neutralizing activity observed suggests that vaccines might require strategies to selectively target the most potent neutralizing epitopes.


Asunto(s)
Anticuerpos Neutralizantes/farmacología , Infecciones por Coronavirus/inmunología , Peptidil-Dipeptidasa A/genética , Neumonía Viral/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/farmacología , Antígenos Virales/inmunología , Chlorocebus aethiops , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Epítopos/inmunología , Humanos , Inmunidad Celular/inmunología , Pandemias , Peptidil-Dipeptidasa A/inmunología , Neumonía Viral/patología , Neumonía Viral/virología , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Linfocitos T Colaboradores-Inductores/inmunología , Células Vero/inmunología
19.
ACS Chem Neurosci ; 11(15): 2149-2151, 2020 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-32662981

RESUMEN

Acanthamoeba and macrophages exhibit significant parallels in biochemical, physiological, cellular, and functional aspects. Given the ability of Acanthamoeba to contribute to the evolutionary gain of pathogenicity of a variety of microbial pathogens, here we propose the use of Acanthamoeba as a paradigm to study SARS-CoV-2 pathogenicity, infectivity, and evasion of cellular immune defenses.


Asunto(s)
Acanthamoeba/inmunología , Betacoronavirus , Infecciones por Coronavirus/inmunología , Inmunidad Celular/inmunología , Fagocitos/inmunología , Neumonía Viral/inmunología , Animales , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/transmisión , Humanos , Pandemias , Fagocitos/patología , Fagocitosis/inmunología , Neumonía Viral/patología , Neumonía Viral/transmisión
20.
Medicine (Baltimore) ; 99(27): e21010, 2020 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-32629720

RESUMEN

The net level of immunosuppression in kidney transplant recipients is difficult to assess. QuantiFERON Monitor (QFM) is an in vitro diagnostic test that detects interferon-γ (IFN-γ) release in peripheral blood. The aim of our study was to compare QFM testing results in stable kidney transplant recipients and kidney transplant recipients with infection, in a single-centre cohort.We enrolled 71 kidney transplant recipients from our transplantation centre. They were divided into 2 groups according to clinical presentation (Stable kidney transplant recipients or Infection).There were no significant differences in interferon-γ release between the 2 groups (Stable kidney transplant recipients 140.59 ±â€Š215.28 IU/ml, Infection group 78.37 ±â€Š197.03 IU/ml, P = .24). A further analysis revealed that kidney transplant recipients presenting with bacterial infection had significantly lower IFN-γ release when compared to stable kidney transplant recipients (26.52 ±â€Š42.46 IU/ml vs 140.59 ±â€Š215.28 IU/ml, P = .04).Kidney transplant recipients presenting with bacterial infection had lower IFN-γ release when compared to stable kidney transplant recipients. The QFM test may be useful as a tool to help guide immunosuppression dosing in kidney transplant recipients, but further studies are required to confirm its diagnostic value.


Asunto(s)
Inmunosupresión/efectos adversos , Ensayos de Liberación de Interferón gamma/métodos , Interferón gamma/sangre , Adulto , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Inmunidad Celular/inmunología , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Receptores de Trasplantes/estadística & datos numéricos
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