Evaluation of cross-reactive antigens as determinants of cross-bactericidal activity in pathogenic and commensal...

Area of Science:

• Microbiology
• Immunology
• Bacteriology

Background:

• Neisseria meningitidis is a significant human pathogen.
• Outer membrane vesicles (OMVs) are crucial for vaccine development.
• Antigenic cross-reactivity between Neisseria species is well-documented.

Purpose of the Study:

• To investigate the cross-bactericidal activity of antisera against Neisseria meningitidis OMVs.
• To determine if antigenic cross-reactivity predicts complement-mediated killing.
• To identify the nature of epitopes responsible for bactericidal activity.

Main Methods:

• Raising antisera against OMVs from invasive, carrier, and commensal Neisseria and Moraxella catarrhalis species.
• Assaying antisera for cross-bactericidal activity on Neisseria meningitidis strains.
• Performing antibody titrations, isotyping, and Western-blotting with denatured proteins.

Main Results:

• Complement-mediated killing showed highly variable patterns, not predictable by Western-blotting antigenic cross-reactivity.
• Sera raised against Neisseria meningitidis OMVs exhibited significant cross-bactericidal activity.
• Antibody titrations and isotyping suggested conformational or shared epitopes, undetectable by Western-blotting, are responsible for most bactericidal activity.

Conclusions:

• Antigenic cross-reactivity of major outer membrane proteins does not reliably predict bactericidal activity against Neisseria meningitidis.
• Conformational or shared epitopes, not typically detected by Western-blotting, play a critical role in the complement-mediated killing of Neisseria meningitidis.
• Understanding these epitopes is crucial for developing effective vaccines against Neisseria meningitidis.