Title:
|
Antibody responses to the major outer membrane protein of Chlamydia trachomatis
|
The major outer membrane protein (MOMP) of C. trachomatis is the main candidate for the production of a sub-unit vaccine against trachoma. MOMP contains four variable segments (VS1-VS4) evenly interspersed by five constant regions. Monoclonal and polyclonal antibodies to serovar-, sub species-, and species-specific epitopes from the variable segments neutralise Chlamydia in vitro and in vivo. This thesis describes the immunogenicity of synthetic MOMP-specific peptides, recombinant fragments of MOMP (rMOMP) and chemically conjugated tMOMP-peptide constructs in rabbits and mice. Rabbit antisera to synthetic peptides corresponding to the serovar-, sub species- and species-specific epitopes of serovar B MOMP recognised cognate epitopes on native Chlamydia. Immunisation of rabbits with a serovar L1, ³/₄ length, recombinant fragment of MOMP (rMOMP) elicited antisera that bound to intact C. trachomatis in a species-specific manner. Serovar-specific peptides from trachoma serovars A, B and C were chemically conjugated to a backbone of L1 ³/₄ tMOMP, generating antisera reactive with the rMOMP backbone, the haptenic peptides and serovar A, B and C and L1 C. trachomatis Experiments were undertaken to investigate the ability of rMOMP-peptide conjugates to prime mice to produce a heterotypic anamnestic antibody response after secondary immunisation with a single serovar of C. trachomatis. Mice were primed in the absence of adjuvant with rMOMP conjugated to serovar-species B cell determinants from serovars A, B and C and a known human T cell epitope. Mice boosted with C. trachomatis serovar L1 produced secondary antibody responses specific to the serovar A, B and C-specific B-cell peptides. The presence of the human T cell epitope augmented anamnestic anti-B-cell peptide responses homologous to the challenge organism.
|