Bordetella pertussis fimbriae (Fim): relevance for vaccines

Abstract

Bordetella pertussis produces two serologically distinct fimbriae, Fim2 and Fim3. Expression of these antigens is governed by the BvgA/S system and by the length of a poly(C) tract in the promoter of each gene. Fim2 and Fim3 are important antigens for whole cell pertussis vaccines as clinical trials have shown an association of anti-fimbriae antibody-mediated agglutination and protection. The current five component acellular pertussis vaccine contains co-purified Fim2/3 and provided good efficacy in clinical trials with the anti-Fim antibody response correlating with protection when pre and post exposure antibody levels were analysed. The predominant serotype of B. pertussis isolates has changed over time in most countries but it is not understood whether this is vaccine-driven or whether serotype is linked to the prevailing predominant genotype. Recent studies have shown that both Fim2 and Fim3 are expressed during infection and that Fim2 is more immunogenic than Fim3 in the acellular vaccine.

Keywords::

• antibody
• Bordetella pertussis
• Fim2
• Fim3
• fimbriae
• serotype
• vaccine

Acknowledgements

The authors would like to thank F Alexander (Public Health England, Porton Down) for helpful discussions and N Fry (Pertussis Reference Laboratory, Public Health England, Colindale for recent UK serotype data.

Financial & competing interests disclosure

A Gorringe has been the Principal Investigator in research grants funded by Sanofi Pasteur and GlaxoSmithKline. The authors are employees of Public Health England. No other funding has been received. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Fim2 and Fim3 are important Bordetella pertussis antigens with a role in adhesion and in the protective immune response provided by both whole-cell and acellular pertussis vaccines.

• The role of FimD in the structure of fimbriae and in disease pathogenesis is poorly understood.

• Shifts in serotype have been observed in most countries over time. It is not understood to what extent this is driven by immune pressure or linkage of serotype to the predominant genotype.

• The relevance of Fim2 and Fim3 polymorphisms for vaccine immune responses remains unknown.

• Fim2 and Fim3 content in whole-cell pertussis vaccines should be carefully monitored and the immune response to both antigens should be confirmed.

• Fim3 is less immunogenic than Fim2 in an acellular vaccine. Research should focus on understanding the differences between Fim2 and Fim3 and on improving the Fim3 response as this is currently the predominant serotype in most countries where data are available.

• The initial vaccines that children receive appear to influence the breadth of immune response to subsequent vaccination or natural exposure. Children primed with vaccines without fimbriae mount a poor response to these antigens when infected. It will be a challenge to develop new booster vaccines to broaden and prolong the immune response with continued use of current acellular vaccines in infancy.

• The challenge for new pertussis vaccines is to provide both long-term protection from disease and also to prevent acquisition and transmission of B. pertussis. As antifimbriae antibodies may act to prevent adhesion of the organism to the surface of epithelial cells, Fim2 and Fim3 may have an important role in vaccines that can provide herd protection.