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Antibodies recognizing a variety of different structural motifs on meningococcal Lip antigen fail to demonstrate
C R Tinsley1, M Virji, J E Heckels
1Department of Microbiology, Southampton University Medical School, Southampton General Hospital, UK.
Abstract:
The neisserial Lip antigen is a conserved antigen associated with the pathogenic Neisseria species, and is composed of multiple repeats of a consensus pentapeptide. A series of monoclonal antibodies reacting with meningococcal Lip antigen were subjected to epitope mapping, using solid-phase synthetic peptides based on the consensus repeat sequence. The antibodies were found to recognize different continuous epitopes based on the consensus sequence. One monoclonal antibody was utilized in affinity chromatography to obtain purified Lip antigen and the antigen was used for immunization of mice. The resulting antisera did not recognize Lip antigen on Western blots but reacted specifically with Lip antigen in immune precipitation experiments, indicating that the predominant polyclonal immune response was directed against conformational epitopes. Despite the diversity of both continuous and conformational epitopes recognized by the antibodies produced, none of the antibodies demonstrated the ability to promote complement-mediated bactericidal activity. Thus despite its initial apparent promise as a potential vaccine candidate the case for the inclusion of Lip antigen in vaccine formulation cannot be supported at present.
Insights
The neisserial Lip antigen, crucial for pathogenic Neisseria, has diverse epitopes but doesn't induce bactericidal activity. Current findings do not support its use in vaccines.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- The neisserial Lip antigen is a conserved component of pathogenic Neisseria species.
- It is characterized by multiple repeats of a consensus pentapeptide sequence.
Purpose of the Study:
- To investigate the epitopes of the neisserial Lip antigen.
- To assess its potential as a vaccine candidate by evaluating bactericidal activity.
Main Methods:
- Epitope mapping using solid-phase synthetic peptides and monoclonal antibodies.
- Affinity chromatography for Lip antigen purification.
- Immunization of mice and characterization of immune response via Western blots and immune precipitation.
Main Results:
- Monoclonal antibodies recognized distinct continuous epitopes on the Lip antigen.
- Polyclonal antisera primarily targeted conformational epitopes.
- No antibodies generated complement-mediated bactericidal activity against Neisseria.
Conclusions:
- The neisserial Lip antigen possesses diverse continuous and conformational epitopes.
- Despite epitope characterization, the Lip antigen failed to elicit a bactericidal immune response.
- The Lip antigen is not currently supported as a viable vaccine candidate.