Jones, H.E.; (2004) Immune responses to and adjuvant properties of bacterial capsular polysccharides. Doctoral thesis , University of London.

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Abstract

Complement plays an important role in the humoral response to protein antigens, but its role in anti-capsular antibody responses is unclear. The immunogenicity of a panel of twelve CPSs from S. pneumoniae was investigated in mice deficient in complement receptors 1 and 2 (CD35/CD21, respectively). With the exception of serotype 4, IgM anti-polysaccharide responses were not dependent on the presence of CD35/CD21. In contrast IgG anti-polysaccharide responses, which were infrequently and variably elicited in C57BL/6 mice, were critically dependent on the presence of CD21/CD35. Although classified as T-independent type 2 (TI-2) antigens, antibody responses to pneumococcal CPSs, except serotype 4, were different from those to dinitrophenol (DNP)-Ficoll, a model TI-2 antigen. Our results indicated that complement plays a critical role in IgG anti-polysaccharide and anti-hapten responses. However IgM anti-pneumococcal CPS responses, with the only one exception, were surprisingly complement-independent. Our findings establish a differential role of complement in humoral responses to a model TI-2 antigen and clinically relevant polysaccharide antigens. In addition to the studies of S. pneumoniae CPSs, the adjuvant properties of CPSs from K. pneumoniae were also invesitgated. Several K. pneumoniae CPS preparations, in particular K1 and K3, have been reported to possess potent immunomodulatory properties. However the purity of CPSs used was not investigated adequately. We modified previously established methods of CPS purification in order to obtain highly purified CPSs for our studies. Pure CPSs with molecular weights of 1-2 x 106 daltons failed to augment the antibody response to chicken gamma globulin (CGG) when used as an adjuvant in mice. In vitro studies also demonstrated that crude but not highly purified CPSs induced the proliferation of or cytokine production from splenocytes from normal and LPS-hyporesponsive mice. The active component (s) in crude CPSs has not been identified, but it is resistant to heat, protease, nuclease and alkaline treatments. We have also ruled out the possibility that the immunomodulatory effects were due to bacterial DNA or LPS, two common contaminants in these preparations. Since not all the components in CPS extracts from K. pneumoniae have been characterised, further investigations may identify novel adjuvant candidate (s).

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