Depletion of complement has distinct effects on the primary and secondary antibody responses to a conjugate of pneumococcal serotype 14 capsular polysaccharide and a T-cell-dependent protein carrier.
Complement activation plays a critical role in the immune response to T-cell-dependent and T-cell-independent antigens. However, the effect of conjugation of T-cell-dependent protein carriers to T-cell-independent type 2 antigens on the requirement for complement in the humoral immune response to such antigens remains unknown. We studied the role of complement activation on the antibody response of BALB/c mice immunized with the T-cell-independent type 2 antigen serotype 14 pneumococcal capsular polysaccharide (PPS14), either in unmodified form or conjugated to ovalbumin (OVA). In mice immunized with either PPS14 or PPS14-OVA, depletion of endogenous complement at the time of primary immunization by treatment with cobra venom factor (CVF) diminished serum anti-PPS14 concentrations after primary immunization but enhanced antibody responses after secondary immunization. The secondary immunoglobulin G (IgG) anti-PPS14 antibody response after immunization with PPS14-OVA was especially enhanced by complement depletion, was observed at doses as low as 0.2 mug of antigen, and was maximal when CVF was administered within 2 days of immunization. The avidity and opsonophagocytic functions of IgG anti-PPS14 antibodies were comparable in mice immunized with PPS14-OVA with or without complement depletion. Serum anti-PPS14 antibody concentrations were near normal, and the enhancing effects of CVF treatment on the secondary anti-PPS14 antibody response were also apparent in splenectomized mice immunized with PPS14-OVA. These results demonstrate that complement activation can have distinct effects on the primary and secondary antibody responses to a T-cell-independent type 2 antigen, either unmodified or conjugated to a T-cell-dependent protein carrier. These differences should be taken into consideration when using complement to modulate the immune response to vaccines.
Test
Samuel T
ST
Children's Hospital Oakland Research Institute, 5700 Martin Luther King, Jr. Way, Oakland, CA 94609-1673, USA. stest@chori.org
Mitsuyoshi
Joyce K
JK
Hu
Yong
Y
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D016667:Bacterial Capsules / Q000276:immunology*; D003165:Complement System Proteins / Q000502:physiology*; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000276:immunology*; D013156:Splenectomy; D013601:T-Lymphocytes / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
D000907:Antibodies, Bacterial; D004546:Elapid Venoms; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; C016310:cobra venom factor; C056696:pneumococcal polysaccharide, type 14; D010047:Ovalbumin; D003165:Complement System Proteins