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Infection and Immunity, May 2001, p. 3031-3040, Vol. 69, No. 5
Children's Hospital Oakland Research
Institute, Oakland, California 94609-1673
Received 24 August 2000/Returned for modification 11 October
2000/Accepted 20 February 2001
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.
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.5.3031-3040.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Increased Immunogenicity and Induction of Class
Switching by Conjugation of Complement C3d to Pneumococcal Serotype 14 Capsular Polysaccharide
*
Corresponding author. Mailing address: Children's
Hospital Oakland Research Institute, 5700 Martin Luther King, Jr. Way,
Oakland, CA 94609-1673. Phone: (510) 450-7630. Fax: (510) 450-7910. E-mail: stest{at}chori.org.
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