Variation of the factor H-binding protein of Neisseria meningitidis

Area of Science:

• Microbiology and Immunology
• Vaccine Development
• Genetics and Molecular Biology

Background:

• Current meningococcal vaccines are limited, particularly against serogroup B, due to challenges in targeting its capsule.
• Subcapsular antigens, such as outer-membrane proteins (OMPs), are promising vaccine candidates but exhibit significant antigenic variability.
• Factor H-binding protein (fHbp) is a key OMP included in developing meningococcal vaccines, necessitating an understanding of its diversity.

Purpose of the Study:

• To investigate the diversity of the fHbp gene and protein in Neisseria meningitidis isolates.
• To establish a nomenclature scheme for cataloging fHbp diversity.
• To analyze selection pressures and recombination within the fHbp gene to understand antigenic variation.

Main Methods:

• Surveyed a representative sample of meningococcal isolates to analyze fHbp gene and protein sequences.
• Developed a unified nomenclature system to classify the observed fHbp diversity.
• Performed sequence analysis to detect recombination and positive selection acting on fHbp alleles.

Main Results:

• Confirmed that fHbp variability is structured into two to three major groups with numerous alleles, associated with specific meningococcal clonal complexes and serogroups.
• Established a nomenclature scheme that effectively catalogues the identified fHbp diversity.
• Demonstrated positive selection, particularly in the C-terminal region and epitope-associated areas of fHbp, indicating immune-driven antigenic variation.

Conclusions:

• The structured diversity of fHbp presents a challenge but also provides a framework for developing more effective serogroup B meningococcal vaccines.
• Understanding the genetic basis of fHbp antigenic variation is essential for designing vaccines that elicit broad and durable immune responses.
• The identified selection pressures highlight specific regions of fHbp that are critical targets for immune evasion and vaccine development.