Immunization with LytB protein of Streptococcus pneumoniae activates complement-mediated phagocytosis and induces protection against pneumonia and sepsis

The cell wall glucosaminidase LytB of Streptococcus pneumoniae is a surface exposed protein involved in daughter cell separation, biofilm formation and contributes to different aspects of the pathogenesis process. In this study we have characterized the antibody responses after immunization of mice...

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Detalles Bibliográficos
Autores: Ruiz, Susana, Domenech, Mirian, Antequera, María Luisa, García, Pedro, García, Ernesto, Corsini, Bruno, Aguinagalde, Leire, Fenoll, Asuncion, Yuste, Jose Enrique
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/10341
Acceso en línea:http://hdl.handle.net/20.500.12105/10341
Access Level:acceso abierto
Palabra clave:Phagocytosis
Adjuvants, Immunologic
Aluminum Hydroxide
Animals
Antibodies, Bacterial
Complement System Proteins
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Immunoglobulin G
Immunologic Factors
Male
Mice, Inbred BALB C
N-Acetylmuramoyl-L-alanine Amidase
Neutrophils
Pneumococcal Infections
Pneumococcal Vaccines
Pneumonia, Bacterial
Sepsis
Streptococcus pneumoniae
Treatment Outcome
Descripción
Sumario:The cell wall glucosaminidase LytB of Streptococcus pneumoniae is a surface exposed protein involved in daughter cell separation, biofilm formation and contributes to different aspects of the pathogenesis process. In this study we have characterized the antibody responses after immunization of mice with LytB in the presence of alhydrogel as an adjuvant. Enzyme-linked immunosorbent assays measuring different subclasses of immunoglobulin G, demonstrated that the antibody responses to LytB were predominantly IgG1 and IgG2b, followed by IgG3 and IgG2a subclasses. Complement-mediated immunity against two different pneumococcal serotypes was investigated using sera from immunized mice. Immunization with LytB increased the recognition of S. pneumoniae by complement components C1q and C3b demonstrating that anti-LytB antibodies trigger activation of the classical pathway. Phagocytosis assays showed that serum containing antibodies to LytB stimulates neutrophil-mediated phagocytosis against S. pneumoniae. Animal models of infection including invasive pneumonia and sepsis were performed with two different clinical isolates. Vaccination with LytB increased bacterial clearance and induced protection demonstrating that LytB might be a good candidate to be considered in a future protein-based vaccine against S. pneumoniae.