The goals of this application are the dissection of the relative functional role of the major outer membrane protein (MOMP) variant sequence (VS) regions and CAL as immune targets of antibody mediated neutralization, and the evaluation of the human humoral response of trachoma tear samples to sequence-specific chlamydial epitopes and correlation of this data to neutralization capability and clinical status. The broad, long-term objectives are development of a basic understanding of immune mechanisms elicited during natural infection for developing and evaluating strategies for immune prophylactic intervention.
The specific aims are: 1) Characterize the antigenicity and immunogenicity of CAL. Antigenicity of CAL will be tested using natural CAL purified from chlamydia infected tissue cultures and probed using human immune sera. Antigenic specificity will be investigated using monoclonal antibodies produced to CAL. Immunogenicity of native CAL will be evaluated by immunization of animals and tested by neutralization. The mechanism and efficacy of neutralization by anti-CAL antibodies will be compared to anti-MOMP antibodies. 2) Systematically characterize the humoral immune responses to Chlamydia trachomatis infection. The focus is comparison of humoral responses evaluated by MOMP-sequence defined immunoassay with special emphasis on the functional role of antibodies to defined MOMP regions using an in vitro infectivity neutralization assay to dissect efficacious neutralization targets. 3) Determine the tear antibody repertoire specificities to chlamydial antigens and tear antibody functional capabilities in neutralization. Antibodies in tears from trachoma patients will be evaluated for IgG and IgA (sIgA) and their quantity, epitopic specificities and neutralization abilities determined. Evaluate the relationship of tear antibody specificity, Ig class, and function with infection status and infecting strain.
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