title: Immunization with LytB protein of Streptococcus pneumoniae activates complement-mediated phagocytosis and induces protection against pneumonia and sepsis.
abstract: 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.
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Corsini
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.
authors.forename: Leire
authors.initials: L
authors.lastname: Aguinagalde
authors.affiliation: Centro de Investigaciones Biológicas (CIB-CSIC), 28040 Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Ruiz
authors.affiliation: Centro de Investigaciones Biológicas (CIB-CSIC), 28040 Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.
authors.forename: Mirian
authors.initials: M
authors.lastname: Domenech
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Antequera
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: Fenoll
authors.affiliation: Centro de Investigaciones Biológicas (CIB-CSIC), 28040 Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: García
authors.affiliation: Centro de Investigaciones Biológicas (CIB-CSIC), 28040 Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: García
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain. Electronic address: jyuste@isciii.es.
authors.forename: Jose
authors.initials: J
authors.lastname: Yuste
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D003165:Complement System Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000008:administration & dosage / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000517:prevention & control*; D018805:Sepsis / Q000276:immunology / Q000517:prevention & control*; D013296:Streptococcus pneumoniae / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007155:Immunologic Factors; D022242:Pneumococcal Vaccines; D000536:Aluminum Hydroxide; D003165:Complement System Proteins; C119964:LytB protein, Streptococcus; D009238:N-Acetylmuramoyl-L-alanine Amidase
keywords: Cell wall hydrolase; Complement immunity; LytB; Phagocytosis; Streptococcus pneumoniae; Vaccine protein