Distinct binding and immunogenic properties of the gonococcal homologue of meningococcal factor h binding protein

Area of Science:

• Bacteriology
• Immunology
• Vaccine Development

Background:

• Neisseria meningitidis causes sepsis and meningitis by evading complement-mediated killing using factor H binding protein (fHbp).
• fHbp variants (V1, V2, V3) elicit strain-specific immunity, limiting vaccine efficacy.
• High-affinity factor H binding to fHbp can also dampen immune responses.

Purpose of the Study:

• To investigate the potential of a Neisseria gonorrhoeae homologue of fHbp (Ghfp) as a universal vaccine candidate against Neisseria meningitidis.

Main Methods:

• Investigated Ghfp expression and factor H binding in Neisseria gonorrhoeae.
• Analyzed Ghfp's ability to elicit cross-protective immune responses against Neisseria meningitidis fHbp variants.
• Assessed serum bactericidal activity of anti-Ghfp antibodies against clinical isolates.

Main Results:

• Ghfp is not expressed on the gonococcal surface and does not bind factor H.
• Specific amino acid substitutions in Ghfp confer factor H binding, while key residues in V3 fHbp are essential for binding.
• Immune responses against Ghfp recognize all fHbp variants (V1, V2, V3) and demonstrate serum bactericidal activity against diverse Neisseria meningitidis strains.

Conclusions:

• Ghfp is a promising vaccine candidate for Neisseria meningitidis, offering broad protection across fHbp variants.
• Targeting Ghfp may overcome the limitations of current fHbp-based vaccines due to its ability to elicit cross-protective immunity.