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Frequency of factor H-binding protein modular groups and susceptibility to cross-reactive bactericidal activity in

Rolando Pajon1, Peter T Beernink, Lee H Harrison

  • 1Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.

Vaccine
|January 2, 2010
PubMed

Insights

Meningococcal factor H-binding protein (fHbp) has a modular structure, crucial for designing effective group B vaccines. Understanding fHbp variants and their expression is key to developing broad protection against meningococcal disease.

Area of Science:

  • Microbiology
  • Vaccinology
  • Immunology

Background:

  • Meningococcal factor H-binding protein (fHbp) is a key vaccine target.
  • fHbp exhibits sequence variability, classified into groups and sub-families.
  • Previous work established a modular architecture for fHbp.

Purpose of the Study:

  • To analyze new fHbp variants and classify them based on modular architecture.
  • To investigate the prevalence of different fHbp modular groups in invasive meningococcal disease isolates.
  • To assess the impact of fHbp modular groups and expression levels on vaccine-induced bactericidal activity.

Main Methods:

  • Sequence analysis of 172 new fHbp variants from public databases.
  • Classification of variants into previously defined modular groups.
  • Analysis of invasive group B isolates from the U.S. and Europe.
  • Testing mouse antisera against recombinant fHbp from different modular groups.

Main Results:

  • 172 new fHbp variants were classified into six previously defined modular groups.
  • Modular group I was most common overall, while group IV was prevalent in UK isolates but rare in U.S. isolates.
  • Antisera showed modular group-specific activity against low-expressing strains and broader activity against high-expressing strains.

Conclusions:

  • The modular architecture of fHbp is confirmed.
  • Both modular group and fHbp expression influence susceptibility to bactericidal antibodies.
  • Understanding fHbp modularity is vital for designing broadly protective group B vaccines regionally.

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