title: Complement dependency of splenic localization of pneumococcal polysaccharide and conjugate vaccines.
abstract: The immune response to polysaccharides is initiated when polysaccharides bind complement factor C3d, and these polysaccharide-C3d complexes subsequently localize on splenic marginal zone B cells strongly expressing CD21 (complement receptor 2). Infants and children under the age of 2 years have low or absent expression of CD21 on their marginal zone B cells, and consequently do not adequately respond to polysaccharides. In contrast, polysaccharide-protein conjugate vaccines are able to induce antibodies at this young age. Conjugate vaccines apparently overcome the necessity for CD21-C3d interaction for an antipolysaccharide immune response. We demonstrate in a rat model that localization of pneumococcal polysaccharides on splenic marginal zone B cells indeed is complement dependent. We also show that pneumococcal conjugates do not specifically localize on splenic marginal zone B cells and that splenic localization of polysaccharide conjugates is independent of the presence of complement. Thus, the induction of antipolysaccharide antibodies by conjugate vaccines apparently can occur independently of CD21-C3d interaction. These basic findings may explain the effectiveness of conjugated vaccines in young children and may open the way for their application in other patient groups.
authors.affiliation: Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, the Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Breukels
authors.forename: A
authors.initials: A
authors.lastname: Zandvoort
authors.forename: G T
authors.initials: GT
authors.lastname: Rijkers
authors.forename: M E
authors.initials: ME
authors.lastname: Lodewijk
authors.forename: P A
authors.initials: PA
authors.lastname: Klok
authors.forename: G
authors.initials: G
authors.lastname: Harms
authors.forename: W
authors.initials: W
authors.lastname: Timens
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015933:Complement C3d / Q000276:immunology* / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000276:immunology; D004546:Elapid Venoms / Q000276:immunology; D007150:Immunohistochemistry; D008099:Liver / Q000276:immunology; D008297:Male; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology* / Q000493:pharmacokinetics; D011135:Polysaccharides, Bacterial / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D018074:Vaccines, Conjugate / Q000276:immunology / Q000378:metabolism
chemical_list: D004546:Elapid Venoms; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; D015933:Complement C3d