Antibody responses to the major outer membrane protein of Chlamydia trachomatis

Ferris, Shirley (1994) Antibody responses to the major outer membrane protein of Chlamydia trachomatis. University of Southampton, Doctoral Thesis.

Abstract

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.

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