title: Increased immunogenicity and induction of class switching by conjugation of complement C3d to pneumococcal serotype 14 capsular polysaccharide.
abstract: Previous studies have demonstrated an adjuvant effect for the C3d fragment of complement C3 when coupled to T-dependent protein antigens. In this study, we examined the antibody response to covalent conjugates of C3d and a T-independent antigen, the capsular polysaccharide of serotype 14 Streptococcus pneumoniae (PPS14). We prepared a conjugate of mouse C3d and PPS14 and compared its immunogenicity with that of a conjugate of PPS14 and ovalbumin (OVA). When BALB/c mice were immunized with PPS14-C3d, there was a significant increase in serum anti-PPS14 concentrations compared with either native PPS14 or control PPS14-glycine conjugates. This was accompanied by a switch in anti-PPS14 from predominantly immunoglobulin M (IgM) to IgG1 by day 25 following primary immunization. Following secondary immunization with PPS14-C3d, there was a marked booster response and a further increase in the ratio of IgG1 to IgM anti-PPS14. Although the primary antibody response to the PPS14-OVA conjugate exceeded that induced by immunization with PPS14-C3d, serum anti-PPS14 concentrations after a second injection of PPS14-C3d were nearly identical to those induced by secondary immunization with PPS14-OVA. Experiments with athymic nude mice suggested that T cells were not required for the adjuvant effect of C3d on the primary immune response to PPS14 but were necessary for enhancement of the memory response after a second injection of PPS14-C3d. These studies show that the adjuvant effects of C3d extend to T-independent antigens as well as T-dependent antigens. As a means of harnessing the adjuvant potential of the innate immune system, C3d conjugates may prove useful as a component of vaccines against encapsulated bacteria.
authors: Children's Hospital Oakland Research Institute, Oakland, California 94609-1673, USA. stest@chori.org
authors: S T
authors: ST
authors: Test
authors: J
authors: J
authors: Mitsuyoshi
authors: C C
authors: CC
authors: Connolly
authors: A H
authors: AH
authors: Lucas
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D015933:Complement C3d / Q000276:immunology*; D005260:Female; D017578:Immunoglobulin Class Switching; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010047:Ovalbumin / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; D015933:Complement C3d; D010047:Ovalbumin