Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.470
Filtrar
1.
Int J Mol Sci ; 22(6)2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33801155

RESUMEN

The causes of otitis media (OM) involve bacterial and viral infection, anatomo-physiological abnormalities of the Eustachian canal and nasopharynx, allergic rhinitis, group childcare centers, second-hand smoking, obesity, immaturity and defects of the immune system, formula feeding, sex, race, and age. OM is accompanied by complex and diverse interactions among bacteria, viruses, inflammatory cells, immune cells, and epithelial cells. The present study summarizes the antibodies that contribute to immune reactions in all types of otitis media, including acute otitis media, otitis media with effusion, and chronic otitis media with or without cholesteatoma, as well as the transcription factors that induce the production of these antibodies. The types and distribution of B cells; the functions of B cells, especially in otorhinolaryngology; antibody formation in patients with otitis media; and antibodies and related transcription factors are described. B cells have important functions in host defenses, including antigen recognition, antigen presentation, antibody production, and immunomodulation. The phenotypes of B cells in the ear, nose, and throat, especially in patients with otitis media, were shown to be CD5low, CD23high, CD43low, B220high, sIgMlow, sIgDhigh, Mac-1low, CD80(B7.1)low, CD86(B7.2)low, and Syndecam-1low. Of the five major classes of immunoglobulins produced by B cells, three (IgG, IgA, and IgM) are mainly involved in otitis media. Serum concentrations of IgG, IgA, and IgM are lower in patients with OM with effusion (OME) than in subjects without otitis media. Moreover, IgG, IgA, and IgM concentrations in the middle ear cavity are increased during immune responses in patients with otitis media. B cell leukemia/lymphoma-6 (Bcl-6) and paired box gene 5 (Pax-5) suppress antibody production, whereas B lymphocyte inducer of maturation program 1 (Blimp-1) and X-box binding protein 1 (XBP-1) promote antibody production during immune responses in patients with otitis media.


Asunto(s)
Susceptibilidad a Enfermedades , Inmunoglobulinas/inmunología , Otitis Media/etiología , Otitis Media/metabolismo , Factores de Transcripción/metabolismo , Animales , Formación de Anticuerpos/inmunología , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Manejo de la Enfermedad , Regulación de la Expresión Génica , Humanos , Inmunoglobulina A/biosíntesis , Inmunoglobulina A/inmunología , Inmunoglobulinas/genética , Otitis Media/diagnóstico
2.
Nat Commun ; 12(1): 2037, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33795692

RESUMEN

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.


Asunto(s)
Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , /inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , /inmunología , Niño , Preescolar , Reacciones Cruzadas/inmunología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Persona de Mediana Edad , Receptores de IgG/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven
3.
Sci Adv ; 7(10)2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33674317

RESUMEN

Limited knowledge exists on immune markers associated with disease severity or recovery in patients with coronavirus disease 2019 (COVID-19). Here, we elucidated longitudinal evolution of SARS-CoV-2 antibody repertoire in patients with acute COVID-19. Differential kinetics was observed for immunoglobulin M (IgM)/IgG/IgA epitope diversity, antibody binding, and affinity maturation in "severe" versus "mild" COVID-19 patients. IgG profile demonstrated immunodominant antigenic sequences encompassing fusion peptide and receptor binding domain (RBD) in patients with mild COVID-19 who recovered early compared with "fatal" COVID-19 patients. In patients with severe COVID-19, high-titer IgA were observed, primarily against RBD, especially in patients who succumbed to SARS-CoV-2 infection. The patients with mild COVID-19 showed marked increase in antibody affinity maturation to prefusion SARS-CoV-2 spike that associated with faster recovery from COVID-19. This study revealed antibody markers associated with disease severity and resolution of clinical disease that could inform development and evaluation of effective immune-based countermeasures against COVID-19.


Asunto(s)
Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Biomarcadores/sangre , /patología , Índice de Severidad de la Enfermedad , Afinidad de Anticuerpos/inmunología , Formación de Anticuerpos/inmunología , /virología , Citocinas/sangre , Células HEK293 , Hospitalización , Humanos , Cambio de Clase de Inmunoglobulina , Cinética , Pruebas de Neutralización , Unión Proteica , Dominios Proteicos , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Carga Viral
4.
JAMA Netw Open ; 4(3): e214302, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33749770

RESUMEN

Importance: Accumulating evidence suggests that children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to manifest mild symptoms and are at a lower risk of developing severe respiratory disease compared with adults. It remains unknown how the immune response in children differs from that of adolescents and adults. Objective: To investigate the association of age with the quantity and quality of SARS-CoV-2 antibody responses. Design, Setting, and Participants: This cross-sectional study used 31 426 SARS-CoV-2 antibody test results from pediatric and adult patients. Data were collected from a New York City hospital from April 9 to August 31, 2020. The semiquantitative immunoglobin (Ig) G levels were compared between 85 pediatric and 3648 adult patients. Further analysis of SARS-CoV-2 antibody profiles was performed on sera from 126 patients aged 1 to 24 years. Main Outcomes and Measures: SARS-CoV-2 antibody positivity rates and IgG levels were evaluated in patients from a wide range of age groups (1-102 years). SARS-CoV-2 IgG level, total antibody (TAb) level, surrogate neutralizing antibody (SNAb) activity, and antibody binding avidity were compared between children (aged 1-10 years), adolescents (aged 11-18 years), and young adults (aged 19-24 years). Results: Among 31 426 antibody test results (19 797 [63.0%] female patients), with 1194 pediatric patients (mean [SD] age, 11.0 [5.3] years) and 30 232 adult patients (mean [SD] age, 49.2 [17.1] years), the seroprevalence in the pediatric (197 [16.5%; 95% CI, 14.4%-18.7%]) and adult (5630 [18.6%; 95% CI, 18.2%-19.1%]) patient populations was similar. The SARS-CoV-2 IgG level showed a negative correlation with age in the pediatric population (r = -0.45, P < .001) and a moderate but positive correlation with age in adults (r = 0.24, P < .001). Patients aged 19 to 30 years exhibited the lowest IgG levels (eg, aged 25-30 years vs 1-10 years: 99 [44-180] relative fluorescence units [RFU] vs 443 [188-851] RFU). In the subset cohort aged 1 to 24 years, IgG, TAb, SNAb and avidity were negatively correlated with age (eg, IgG: r = -0.51; P < .001). Children exhibited higher median (IQR) IgG levels, TAb levels, and SNAb activity compared with adolescents (eg, IgG levels: 473 [233-656] RFU vs 191 [82-349] RFU; P < .001) and young adults (eg, IgG levels: 473 [233-656] RFU vs 85 [38-150] RFU; P < .001). Adolescents also exhibited higher median (IQR) TAb levels, IgG levels, and SNAb activity than young adults (eg, TAb levels: 961 [290-2074] RFU vs 370 [125-697]; P = .006). In addition, children had higher antibody binding avidity compared with young adults, but the difference was not significant. Conclusions and Relevance: The results of this study suggest that SARS-CoV-2 viral specific antibody response profiles are distinct in different age groups. Age-targeted strategies for disease screening and management as well as vaccine development may be warranted.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Afinidad de Anticuerpos/inmunología , Formación de Anticuerpos/inmunología , Factores de Edad , /epidemiología , /métodos , Niño , Correlación de Datos , Estudios Transversales , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , /aislamiento & purificación
5.
Gut ; 70(5): 865-875, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33753421

RESUMEN

OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4ß7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULTS: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSIONS: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Asunto(s)
Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/uso terapéutico , /inmunología , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pruebas Serológicas , Reino Unido/epidemiología
6.
Emerg Infect Dis ; 27(4): 1155-1158, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33734962

RESUMEN

Prospective serosurveillance of severe acute respiratory syndrome coronavirus 2 in 1,069 healthcare workers in London, UK, demonstrated that nucleocapsid antibody titers were stable and sustained for <12 weeks in 312 seropositive participants. This finding was consistent across demographic and clinical variables and contrasts with reports of short-term antibody waning.


Asunto(s)
Anticuerpos Antivirales/sangre , Formación de Anticuerpos/inmunología , Personal de Salud/estadística & datos numéricos , Adulto , /epidemiología , /métodos , Femenino , Humanos , Londres/epidemiología , Masculino , Fosfoproteínas/inmunología , Seroconversión , Estudios Seroepidemiológicos
7.
Nat Commun ; 12(1): 1102, 2021 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-33597521

RESUMEN

The four-dengue virus (DENV) serotypes infect several hundred million people annually. For the greatest safety and efficacy, tetravalent DENV vaccines are designed to stimulate balanced protective immunity to all four serotypes. However, this has been difficult to achieve. Clinical trials with a leading vaccine demonstrated that unbalanced replication and immunodominance of one vaccine component over others can lead to low efficacy and vaccine enhanced severe disease. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a live attenuated tetravalent DENV vaccine (TV003), which is currently being tested in phase 3 clinical trials. Here we report, our study to determine if TV003 stimulate balanced and serotype-specific (TS) neutralizing antibody (nAb) responses to each serotype. Serum samples from twenty-one dengue-naive individuals participated under study protocol CIR287 (ClinicalTrials.gov NCT02021968) are analyzed 6 months after vaccination. Most subjects (76%) develop TS nAbs to 3 or 4 DENV serotypes, indicating immunity is induced by each vaccine component. Vaccine-induced TS nAbs map to epitopes known to be targets of nAbs in people infected with wild type DENVs. Following challenge with a partially attenuated strain of DENV2, all 21 subjects are protected from the efficacy endpoints. However, some vaccinated individuals develop post challenge nAb boost, while others mount post-challenge antibody responses that are consistent with sterilizing immunity. TV003 vaccine induced DENV2 TS nAbs are associated with sterilizing immunity. Our results indicate that nAbs to TS epitopes on each serotype may be a better correlate than total levels of nAbs currently used for guiding DENV vaccine development.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra el Dengue/inmunología , Virus del Dengue/inmunología , Dengue/inmunología , Formación de Anticuerpos/inmunología , Especificidad de Anticuerpos/inmunología , Dengue/prevención & control , Dengue/virología , Vacunas contra el Dengue/administración & dosificación , Virus del Dengue/clasificación , Epítopos/inmunología , Humanos , Serotipificación , Especificidad de la Especie , Resultado del Tratamiento , Vacunación/métodos , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología
8.
Poult Sci ; 100(4): 101001, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33610897

RESUMEN

Newcastle disease (ND) is one of the classic viral infections of poultry which resists all the efforts of eradication. Newcastle disease virus (NDV) strain ZG1999HDS was isolated during the outbreak in 1,999 at a broiler farm in Croatia. Previous trials in chickens confirmed it to be a lentogenic pathotype and immunogenic by stimulating humoral and cell mediated immunity. Further characterization by deduced amino acid sequence at the cleavage site of fusion protein confirmed its lentogenic nature, and in vitro tests its oncolytic capacity. Owing to its immunogenicity, strain ZG1999HDS is considered for vaccine development. In this study, 1-day-old chicks were vaccinated using strain ZG1999HDS oculonasally or by nebulization. Strain ZG1999HDS induced humoral immune response in both immunized groups The cell-mediated immune response occurred earlier in the group immunized by nebulization, as shown by a higher frequency rate of T and B lymphocytes, and significantly higher expression of IFN-α in respiratory organs and IFN-γ expression in the spleen. Viral genomic RNA was not detected in investigated organs. Thus, NDV strain ZG1999HDS is immunogenic when administered by means of nebulization or oculonasally without any adverse effects and is therefore suitable for further research and vaccine development. Further research is needed regarding its tropism.


Asunto(s)
Inmunidad Humoral , Enfermedad de Newcastle , Virus de la Enfermedad de Newcastle , Enfermedades de las Aves de Corral , Vacunas Virales , Animales , Formación de Anticuerpos/inmunología , Pollos , Inmunidad Humoral/inmunología , Enfermedad de Newcastle/inmunología , Enfermedad de Newcastle/prevención & control , Virus de la Enfermedad de Newcastle/inmunología , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/prevención & control
9.
Nat Commun ; 12(1): 1203, 2021 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-33619277

RESUMEN

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.


Asunto(s)
Algoritmos , Reacciones Cruzadas/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Inmunidad , Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Animales , Formación de Anticuerpos/inmunología , Epítopos/inmunología , Femenino , Humanos , Gripe Humana/sangre , Gripe Humana/inmunología , Gripe Humana/virología , Pulmón/patología , Pulmón/virología , Masculino , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/sangre , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/virología , Porcinos , Linfocitos T/inmunología , Vacunación , Pérdida de Peso
10.
mSphere ; 6(1)2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-33627511

RESUMEN

The majority of infections with SARS-CoV-2 are asymptomatic or mild without the necessity of hospitalization. It is of importance to reveal if these patients develop an antibody response against SARS-CoV-2 and to define which antibodies confer virus neutralization. We conducted a comprehensive serological survey of 49 patients with a mild course of disease and quantified neutralizing antibody responses against a clinical SARS-CoV-2 isolate employing human cells as targets. Four patients (8%), even though symptomatic, did not develop antibodies against SARS-CoV-2, and two other patients (4%) were positive in only one of the six serological assays employed. For the remaining 88%, antibody response against the S protein correlated with serum neutralization whereas antibodies against the nucleocapsid were poor predictors of virus neutralization. None of the sera enhanced infection of human cells with SARS-CoV-2 at any dilution, arguing against antibody-dependent enhancement of infection in our system. Regarding neutralization, only six patients (12%) could be classified as high neutralizers. Furthermore, sera from several individuals with fairly high antibody levels had only poor neutralizing activity. In addition, employing a novel serological Western blot system to characterize antibody responses against seasonal coronaviruses, we found that antibodies against the seasonal coronavirus 229E might contribute to SARS-CoV-2 neutralization. Altogether, we show that there is a wide breadth of antibody responses against SARS-CoV-2 in patients that differentially correlate with virus neutralization. This highlights the difficulty to define reliable surrogate markers for immunity against SARS-CoV-2.IMPORTANCE There is strong interest in the nature of the neutralizing antibody response against SARS-CoV-2 in infected individuals. For vaccine development, it is especially important which antibodies confer protection against SARS-CoV-2, if there is a phenomenon called antibody-dependent enhancement (ADE) of infection, and if there is cross-protection by antibodies directed against seasonal coronaviruses. We addressed these questions and found in accordance with other studies that neutralization is mediated mainly by antibodies directed against the spike protein of SARS-CoV-2 in general and the receptor binding site in particular. In our test system, utilizing human cells for infection experiments, we did not detect ADE. However, using a novel diagnostic test we found that antibodies against the coronavirus 229E might be involved in cross-protection to SARS-CoV-2.


Asunto(s)
Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , Infecciones por Coronavirus/inmunología , /inmunología , Adulto , Anticuerpos Neutralizantes/inmunología , Acrecentamiento Dependiente de Anticuerpo/inmunología , Sitios de Unión/inmunología , Femenino , Hospitalización , Humanos , Masculino , Pruebas de Neutralización/métodos , Nucleocápside/inmunología , Estaciones del Año , Pruebas Serológicas/métodos , Glicoproteína de la Espiga del Coronavirus/inmunología , Encuestas y Cuestionarios , Vacunas/inmunología
11.
Nat Commun ; 12(1): 740, 2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33531472

RESUMEN

The COVID-19 pandemic affects more than 81 million people worldwide with over 1.7 million deaths. As the population returns to work, it is critical to develop tests that reliably detect SARS-CoV-2-specific antibodies. Here we present results from a multiplex serology test for assessing the antibody responses to COVID-19. In an initial large cohort, this test shows greater than 99% agreement with COVID-19 PCR test. In a second outpatient cohort consisting of adults and children in Colorado, the IgG responses are more robust in positive/symptomatic participants than in positive/asymptomatic participants, the IgM responses in symptomatic participants are transient and largely fall below the detection limit 30 days after symptom onset, and the levels of IgA against SARS-CoV-2 receptor binding domain are significantly increased in participants with moderate-to-severe symptoms compared to those with mild-to-moderate symptoms or asymptomatic individuals. Our results thus provide insight into serology profiling and the immune response to COVID-19.


Asunto(s)
/inmunología , Inmunoensayo/métodos , /patogenicidad , Adulto , Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , Niño , Estudios de Cohortes , Colorado , Femenino , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Masculino , Persona de Mediana Edad , Pandemias/estadística & datos numéricos , Reacción en Cadena de la Polimerasa , Pruebas Serológicas
12.
Arch Virol ; 166(2): 571-579, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33410993

RESUMEN

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.


Asunto(s)
Infecciones por Herpesviridae/inmunología , Vacunas contra Herpesvirus/inmunología , Enfermedades de los Caballos/inmunología , Caballos/inmunología , Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , Femenino , Enfermedades de los Caballos/virología , Caballos/virología , Inmunidad Humoral/inmunología , Inmunización Secundaria/métodos , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Vacunación/métodos , Vacunas de Productos Inactivados/inmunología
13.
Arthritis Rheumatol ; 73(3): 478-489, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33512094

RESUMEN

OBJECTIVE: To assess the role of STAT4 activation in driving pathogenic follicular helper T (Tfh) cell secretion of the cytokines interleukin-21 (IL-21) and interferon-γ (IFNγ) in murine and human lupus. METHODS: The effect of STAT4-dependent Tfh cell signaling on cytokine production and autoreactive B cell maturation was assessed temporally during the course of lupus in a murine model, with further assessment of Tfh cell gene transcription performed using RNA-Seq technology. STAT4-dependent signaling and cytokine production were also determined in circulating Tfh-like cells in patients with systemic lupus erythematosus (SLE), as compared to cells from healthy control subjects, and correlations with disease activity were assessed in the Tfh-like cells from SLE patients. RESULTS: IL-21- and IFNγ-coproducing Tfh cells expanded prior to the detection of potentially pathogenic IgG2c autoantibodies in lupus-prone mice. Tfh cells transcriptionally evolved during the course of disease with acquisition of a STAT4-dependent gene signature. Maintenance of Tfh cell cytokine synthesis was dependent upon STAT4 signaling, driven by type I IFNs. Circulating Tfh-like cells from patients with SLE also secreted IL-21 and IFNγ, with STAT4 phosphorylation enhanced by IFNß, in association with the extent of clinical disease activity. CONCLUSION: We identified a role for type I IFN signaling in driving STAT4 activation and production of IL-21 and IFNγ by Tfh cells in murine and human lupus. Enhanced STAT4 activation in Tfh cells may underlie pathogenic B cell responses in both murine and human lupus. These data indicate that STAT4 guides pathogenic cytokine and immunoglobulin production in SLE, demonstrating a potential therapeutic target to modulate autoimmunity.


Asunto(s)
Autoanticuerpos/inmunología , Citocinas/inmunología , Interferón Tipo I/inmunología , Lupus Eritematoso Sistémico/inmunología , Factor de Transcripción STAT4/inmunología , /inmunología , Adulto , Animales , Formación de Anticuerpos/inmunología , Autoanticuerpos/biosíntesis , Linfocitos B/inmunología , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunoglobulinas , Interferón gamma/inmunología , Interleucinas/inmunología , Masculino , Ratones Endogámicos MRL lpr , Persona de Mediana Edad , RNA-Seq
14.
PLoS One ; 16(1): e0245207, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33411807

RESUMEN

In the present study, we evaluated adjuvant potential of Poria cocos polysaccharide (PCP) on the Th1-type immune responses of C57/BL6 mice against ovalbumin (OVA). We first determined the effect of PCP on maturation of murine bone marrow derived dendritic cells (BMDCs), PCP significantly upregulated surface expression of MHCII, CD40, CD80, CD86 and enhanced production of IL-6 and IL-12p40. In addition, PCP affected receptor-mediated endocytosis, but not pinocytosis in BMDCs. Furthermore, OVA + PCP immunization induced specific cytotoxic CD8+ T cell killing of OVA (257-264) peptide pulsed cell. When mice were immunized subcutaneously in a week interval with OVA + PCP. Serum were collected for measuring OVA-specific antibody and splenocytes were harvested for analyzing CD69, IFN-γ ELISpot and cytokines production. The result indicated that OVA-specific IgG, IgG2a and IgG1 antibody levels in serum were significantly elevated by PCP compared with control. PCP increased OVA-specific IFN-γ-secreting CD8+, CD4+ T cells, promoted CD8+ T cell proliferation and up-regulated Th-1 type (IFN-γ, IL-2) cytokine production. In conclusion, data suggest that PCP enhanced cellular immune response and possess potential as a vaccine adjuvant for Th1 immune response.


Asunto(s)
Polisacáridos Fúngicos/inmunología , Inmunidad Celular/efectos de los fármacos , Ovalbúmina/inmunología , Células TH1/inmunología , Wolfiporia/química , Animales , Formación de Anticuerpos/inmunología , Células de la Médula Ósea/inmunología , Linfocitos T CD8-positivos/inmunología , Citocinas/inmunología , Células Dendríticas/inmunología , Femenino , Polisacáridos Fúngicos/química , Inmunoglobulina G/inmunología , Ratones
15.
Mol Immunol ; 131: 44-50, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33446391

RESUMEN

BACKGROUND: Peripheral helper T (TPH) cells, a recently defined subset of Th cells, promote B cell differentiation and antibody production in inflamed tissues. This study investigated whether circulating TPH cells are associated with primary biliary cholangitis (PBC), a typical organ-specific autoimmune disease. METHODS: Twenty PBC patients and 20 age- and sex-matched healthy controls (HCs) were recruited. The circulating TPH cell subsets were analyzed by flow cytometry, and the associations of TPH cells with disease activity and plasma cells were determined. Functional analysis was performed using a TPH and B cell coculture experiment. RESULTS: The frequencies of circulating TPH cells, ICOS+ TPH cells, and CD28+ TPH cells were increased in patients with PBC. Furthermore, the ICOS+ TPH cell level was higher in PBC patients with or without cirrhosis than in HCs, and the level decreased after treatment. Moreover, ICOS+ TPH cell levels correlated positively with specific clinical parameters (including anti-mitochondrial antibodies against M2 antigen (AMA-M2), IgM) and plasma cell levels, suggesting that the TPH cell activation status is associated with the severity of PBC. Coculture results revealed an enhanced ability of TPH cells from PBC patients to induce B cell differentiation. CONCLUSIONS: Elevated numbers of TPH cells may be involved in the pathogenesis of PBC, and the activation status of TPH cells is related to the severity of PBC. Additionally, TPH cells can be used as a useful biomarker for evaluating the progression of PBC and may serve as a therapeutic target for PBC patients in the future.


Asunto(s)
Linfocitos B/inmunología , Cirrosis Hepática Biliar/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Adulto , Anciano , Formación de Anticuerpos/inmunología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Antígenos CD28/inmunología , Células Cultivadas , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Células Plasmáticas/inmunología
16.
BMJ Case Rep ; 14(1)2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33514621

RESUMEN

Around the world, with the availability of factor concentrates, patients with haemophilia have undergone major and minor surgeries. Inhibitor development in early postoperative period leading to inadequate factor recovery and ongoing bleeding is a nightmare for both operating surgeon as well as haematologists. We describe a case of an elderly man with mild haemophilia A, who was diagnosed with pancreatic carcinoma and underwent Whipple's procedure. After an uneventful procedure, he developed high-titre inhibitors and bleeding a week after surgery posing major challenges in his management. The case highlights the importance of experienced surgeons, trained haematologists, regular monitoring of factor assay/inhibitors, adequate factor and bypassing-agent support while performing such procedures.


Asunto(s)
Factores de Coagulación Sanguínea/antagonistas & inhibidores , Hemofilia A/inmunología , Neoplasias Pancreáticas/cirugía , Hemorragia Posoperatoria/tratamiento farmacológico , Anciano , Formación de Anticuerpos/inmunología , Factores de Coagulación Sanguínea/inmunología , Factor VIII/administración & dosificación , Factor VIII/uso terapéutico , Resultado Fatal , Hematología/normas , Hemofilia A/complicaciones , Humanos , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Hemorragias Intracraneales/complicaciones , Masculino , Neoplasias Pancreáticas/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/inmunología , Hemorragia Posoperatoria/etiología , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Factores de Riesgo , Cirujanos/estadística & datos numéricos
17.
Nat Med ; 27(2): 270-278, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33335323

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2 and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18-55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.


Asunto(s)
Formación de Anticuerpos/inmunología , Linfocitos T/inmunología , Adolescente , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , /virología , Relación Dosis-Respuesta Inmunológica , Femenino , Humanos , Inmunidad Celular , Inmunidad Humoral , Inmunoglobulina A/inmunología , Inmunoglobulina M/inmunología , Interferón gamma/metabolismo , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Subunidades de Proteína/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunación , Adulto Joven
18.
Methods Mol Biol ; 2183: 9-18, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32959237

RESUMEN

The immunoglobulin capture assay (ICA) enables the enrichment for pathogen-specific plasmablasts from individuals with a confirmed adaptive immune response to vaccination or disseminated infection. Only single recombinant antigens have been used previously as probes in this ICA and it was unclear whether the method was applicable to complex probes such as whole bacterial cells. Here, we describe the enrichment of plasmablasts specific for polysaccharide and protein antigens of both Streptococcus pneumoniae and Neisseria meningitidis using whole formalin-fixed bacterial cells as probes. The modified ICA protocol described here allowed for a pathogen-specific hmAb cloning efficiency of >80%.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/aislamiento & purificación , Especificidad de Anticuerpos/inmunología , Bacterias/inmunología , Inmunoensayo/métodos , Sondas Moleculares , Anticuerpos Antibacterianos/inmunología , Afinidad de Anticuerpos , Formación de Anticuerpos/inmunología , Antígenos Bacterianos/inmunología , Interacciones Huésped-Patógeno , Humanos , Inmunoglobulina G/inmunología , Células Plasmáticas/inmunología , Células Plasmáticas/metabolismo , Streptococcus pneumoniae/inmunología
19.
Nat Med ; 27(2): 279-288, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33335322

RESUMEN

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.


Asunto(s)
Formación de Anticuerpos/inmunología , /inmunología , Inmunización Secundaria , /inmunología , Adolescente , Adulto , Anticuerpos Neutralizantes/inmunología , Relación Dosis-Respuesta a Droga , Vectores Genéticos/inmunología , Humanos , Persona de Mediana Edad , Glicoproteína de la Espiga del Coronavirus/inmunología , Factores de Tiempo , Adulto Joven
20.
Artículo en Inglés | MEDLINE | ID: mdl-33361386

RESUMEN

OBJECTIVE: To discuss the pathogenic and diagnostic relevance of cellular and humoral immune responses against severe acute respiratory syndrome novel coronavirus (SARS-COV-2) and pertinent observations made in progressive multifocal leukoencephalopathy (PML). METHODS: Review of pertinent literature. RESULTS: There is at least 1 precedent for an antibody response against a viral pathogen that fails to provide host protection in the absence of immune-competent CD4+ T cells. PML is an infection of the CNS caused by JC virus (JCV), which commonly occurs during treatment with the therapeutic monoclonal antibody natalizumab. In this context, the humoral immune response fails to prevent JCV reactivation, and elevated anti-JCV serum indices are associated with a higher PML incidence. The more relevant immune-competent cells in host defense against JCV appear to be T cells. T cell-mediated responses are also detectable in convalescing patients with SARS-COV-2 irrespective of the humoral immune response. CONCLUSION: Based on pathogenic lessons learned from PML under natalizumab therapy, we suggest the incorporation of functional assays that determine neutralizing properties of SARS-CoV-2-specific antibodies. In addition, we outline the potential role of T-cell detection assays in determining herd immunity in a given population or in studying therapeutic responses to vaccines.


Asunto(s)
Inmunidad Adaptativa/inmunología , Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , Inmunidad Humoral/inmunología , Leucoencefalopatía Multifocal Progresiva/inmunología , Linfocitos T/inmunología , Humanos , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...