Complement dependency of splenic localization of pneumococcal polysaccharide and conjugate vaccines.
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.
Breukels
M A
MA
Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, the Netherlands.
Zandvoort
A
A
Rijkers
G T
GT
Lodewijk
M E
ME
Klok
P A
PA
Harms
G
G
Timens
W
W
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
D004546:Elapid Venoms; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; D015933:Complement C3d