Importance of (antibody-dependent) complement-mediated serum killing in protection against Bordetella pertussis

Abstract

Pertussis is a highly contagious respiratory disease that is caused by Bordetella pertussis. Despite being vaccine preventable, pertussis rates have been rising steadily over the last decades, even in areas with high vaccine uptake. Recently, experiments with infant baboons indicated that although vaccination with acellular pertussis vaccines prevented disease, no apparent effect was observed on infection and transmission. One explanation may be that current acellular pertussis vaccines do not induce high levels of opsonophagocytic and/or bactericidal activity, implying that engineering of vaccines that promote bacterial killing may improve efficacy. Here, we discuss the importance of complement-mediated killing in vaccine-induced protection against B. pertussis. We first examine how B. pertussis may have evolved different complement evasion strategies. Second, we explore the benefits of opsonophagocytic and/or bactericidal killing in vaccine-induced protection and discuss whether or not inclusion of new opsonophagocytic or bactericidal target antigens in pertussis vaccines may benefit efficacy.

Keywords::

• bactericidal activity
• Bordetella pertussis
• complement system
• immune evasion
• opsonophagocytic killing
• vaccine development

Acknowledgements

The authors are employees of Crucell Hollland B.V., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Department of Bacterial Vaccines Research and Development in Leiden, the Netherlands.

Financial & competing interests disclosure

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

• The incidence of pertussis is increasing and improved vaccines are needed.

• Complement-mediated killing is a highly regulated system important for protection against invading pathogens.

• Complement system is active in the lungs; the site of infection of Bordetella pertussis.

• B. pertussis produces a number of protein and non-protein structures involved in resistance against complement-mediated killing.

• Opsonophagocytic killing seems to be more important as compared with direct serum bactericidal killing for immune protection against B. pertussis.

• Further development and standardization of (human) complement-mediated killing assays for B. pertussis is needed.

• Introduction of new vaccine components that enhance opsonophagocytic and/or bactericidal killing may result in better vaccine-mediated protection against B. pertussis infection.

Notes