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Blocking of bactericidal killing of Neisseria meningitidis by antibodies directed against class 4 outer membrane
A Munkley1, C R Tinsley, M Virji
1Department of Microbiology, University of Southampton Medical School, Southampton General Hospital, U.K.
Abstract:
The class 4 protein of Neisseria meningitidis is a highly conserved outer membrane protein, closely related to the protein PIII of Neisseria gonorrhoea. Monoclonal antibodies SM50 and SM54 raised against PIII also react with class 4 protein but do not promote complement mediated bactericidal killing of meningococci. In addition, mAb SM50 inhibits the anti-meningococcal bactericidal activity both of normal human sera and of mAb SM300, directed against a protective epitope on the class 1 outer membrane protein. The ability of class 4 protein to induce such 'blocking' antibodies suggests that its presence in experimental vaccines, based on meningococcal outer membranes, may be antagonistic to the development of effective bactericidal immunity.
Insights
Neisseria meningitidis class 4 protein may hinder vaccine effectiveness. Antibodies targeting this outer membrane protein can block immune responses, potentially antagonizing bactericidal immunity development in experimental vaccines.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Neisseria meningitidis outer membrane proteins are targets for vaccines.
- Class 4 protein is conserved and related to Neisseria gonorrhoea PIII protein.
Purpose of the Study:
- To investigate the immunological properties of Neisseria meningitidis class 4 protein.
- To assess the potential impact of class 4 protein on vaccine-induced immunity.
Main Methods:
- Monoclonal antibodies (mAbs) SM50 and SM54 were used, raised against PIII.
- Reactivity of mAbs with class 4 protein was tested.
- Complement-mediated bactericidal activity and blocking effects were evaluated.
Main Results:
- mAbs SM50 and SM54 reacted with class 4 protein but did not induce bacterial killing.
- mAb SM50 inhibited normal human serum and mAb SM300 mediated bactericidal activity.
- Class 4 protein induced antibodies that blocked bactericidal activity.
Conclusions:
- The class 4 protein of Neisseria meningitidis can induce blocking antibodies.
- Its inclusion in outer membrane-based vaccines may impede effective bactericidal immunity.
- Further research is needed to understand its role in meningococcal pathogenesis and vaccine design.