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Meningococcal factor H binding proteins in epidemic strains from Africa: implications for vaccine development

Rolando Pajon1, Andrew M Fergus, Oliver Koeberling

  • 1Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California, United States of America.

Plos Neglected Tropical Diseases
|September 13, 2011
PubMed
Abstract

Insights

Native outer membrane vesicle (NOMV) vaccines expressing high levels of factor H binding protein (fHbp) show promise for preventing meningococcal disease in Africa. These NOMV vaccines elicit broader bactericidal activity compared to recombinant fHbp vaccines.

Area of Science:

  • Bacteriology
  • Vaccinology
  • Immunology

Background:

  • Factor H binding protein (fHbp) is a key antigen for vaccines against meningococcal serogroup B.
  • fHbp facilitates bacterial resistance to human factor H (fH) and serum bactericidal activity.
  • Limited data exist on fHbp vaccine potential against African epidemics caused by non-group B meningococci.

Purpose of the Study:

  • To investigate the vaccine-potential of fHbp in African meningococcal isolates.
  • To evaluate the efficacy of recombinant fHbp vaccines and a novel native outer membrane vesicle (NOMV) vaccine.

Main Methods:

  • Analyzed fHbp genes in 106 serogroup A, W-135, and X isolates from Africa.
  • Assessed complement-mediated bactericidal activity of antisera from mice immunized with fHbp vaccines.
  • Compared recombinant fHbp vaccines with a prototype NOMV vaccine over-expressing fHbp.

Main Results:

  • Eighty-one percent of isolates carried prevalent fHbp sequence variants (ID 4/5, 9, 74, or 22/23).
  • Low fHbp expression was observed in some serogroup A and W-135 isolates, while serogroup X isolates showed intermediate/high expression.
  • Recombinant fHbp vaccines showed limited bactericidal activity, while the NOMV fHbp ID 1 vaccine induced broad activity and enhanced fH binding inhibition.

Conclusions:

  • NOMV vaccines with increased fHbp expression generate broader bactericidal antibody responses than recombinant vaccines.
  • NOMV vaccines hold promise for preventing meningococcal disease in Africa.
  • NOMV vaccines could complement existing serogroup A conjugate vaccines.

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