Meningococcal factor H-binding protein variants expressed by epidemic capsular group A, W-135, and X strains from

P T Beernink1, D A Caugant, J A Welsch

  • 1Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA, USA.

Abstract

Insights

Factor H-binding protein (fHbp) is conserved across African meningococcal strains causing epidemics. Vaccines expressing fHbp variants show potential for broad protection against these diverse groups.

Area of Science:

  • Microbiology
  • Vaccinology
  • Epidemiology

Background:

  • Meningococcal epidemics in Africa are primarily driven by serogroup A strains, with W-135 and X also contributing.
  • Factor H-binding protein (fHbp) is a key antigen for serogroup B vaccines, but its role in other serogroups is less understood.

Purpose of the Study:

  • To investigate the presence and characteristics of fHbp in African strains of Neisseria meningitidis serogroups A, W-135, and X.
  • To assess the potential of fHbp as a target for broad-spectrum meningococcal vaccines in Africa.

Main Methods:

  • Analysis of fHbp genes and protein variants in 35 meningococcal isolates (22 group A, 10 group W-135, 3 group X) from African epidemics.
  • Evaluation of amino acid identity and conserved epitopes within fHbp variants.
  • Assessment of bactericidal activity of antibodies generated by fHbp-expressing vaccines in mouse models.

Main Results:

  • All investigated African meningococcal strains (serogroups A, W-135, X) possessed fHbp genes, primarily encoding antigenic variant group 1, with high amino acid identity (92%-100%) within variants.
  • Expressed fHbp proteins contained conserved epitopes recognized by bactericidal monoclonal antibodies.
  • Vaccines based on native outer membrane vesicles expressing fHbp variants demonstrated broad bactericidal activity against epidemic strains.

Conclusions:

  • Factor H-binding protein (fHbp) is a conserved antigen across diverse African meningococcal serogroups causing epidemics.
  • A vaccine targeting fHbp variants has the potential to induce protective immunity against multiple epidemic-causing meningococcal strains in Africa.