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1.
Nat Commun ; 11(1): 4994, 2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-33020485

RESUMEN

Serogroup B meningococcus (MenB) is a leading cause of meningitis and sepsis across the world and vaccination is the most effective way to protect against this disease. 4CMenB is a multi-component vaccine against MenB, which is now licensed for use in subjects >2 months of age in several countries. In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults. The resulting 4CMenB protein antigen fingerprinting allowed the identification of specific human antibody repertoire correlating with the bactericidal response elicited in each subject. This work represents an example of epitope mapping of the immune response induced by a multicomponent vaccine in different age groups with the identification of protective signatures. It shows the high flexibility of this microarray based methodology in terms of high-throughput information and minimal volume of biological samples needed.


Asunto(s)
Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/inmunología , Infecciones Meningocócicas/inmunología , Vacunas Meningococicas/inmunología , Neisseria meningitidis Serogrupo B/inmunología , Adolescente , Adulto , Anticuerpos Antibacterianos/sangre , Niño , Preescolar , Mapeo Epitopo , Humanos , Lactante , Infecciones Meningocócicas/prevención & control , Biblioteca de Péptidos , Análisis por Matrices de Proteínas , Determinación de Anticuerpos Séricos Bactericidas , Adulto Joven
2.
Infect Immun ; 82(11): 4508-17, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25114117

RESUMEN

Previous studies have indicated that group B streptococcus (GBS), a frequent human pathogen, potently induces the release of interleukin-1ß (IL-1ß), an important mediator of inflammatory responses. Since little is known about the role of this cytokine in GBS disease, we analyzed the outcome of infection in IL-1ß-deficient mice. These animals were markedly sensitive to GBS infection, with most of them dying under challenge conditions that caused no deaths in wild-type control mice. Lethality was due to the inability of the IL-1ß-deficient mice to control local GBS replication and dissemination to target organs, such as the brain and the kidneys. Moreover, in a model of inflammation induced by the intraperitoneal injection of killed GBS, a lack of IL-1ß was associated with selective impairment in the production of the neutrophil chemokines CXCL1 and CXCL2 and in neutrophil recruitment to the peritoneal cavity. Decreased blood neutrophil counts and impaired neutrophil recruitment to the brain and kidneys were also observed during GBS infection in IL-1ß-deficient mice concomitantly with a reduction in CXCL1 and CXCL2 tissue levels. Notably, the hypersusceptibility to GBS infection observed in the immune-deficient animals was recapitulated by neutrophil depletion with anti-Gr1 antibodies. Collectively, our data identify a cytokine circuit that involves IL-1ß-induced production of CXCL1 and CXCL2 and leads the recruitment of neutrophils to GBS infection sites. Moreover, our data point to an essential role of these cells in controlling the progression and outcome of GBS disease.


Asunto(s)
Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/metabolismo , Interleucina-1beta/metabolismo , Neutrófilos/fisiología , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/inmunología , Animales , Quimiocina CXCL1/genética , Quimiocina CXCL2/genética , Femenino , Humanos , Interleucina-1beta/genética , Ratones , Ratones Noqueados , Peritonitis/inmunología , Peritonitis/microbiología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Infecciones Estreptocócicas/inmunología
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