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Antigens and Immunity |
Research Laboratory for Infectious Diseases1, Laboratory for Clinical Vaccine Research2 and Laboratory for Vaccine Research3, National Institute of Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, The Netherlands
Eijkman Winkler Institute, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands4
Author for correspondence: Frits R. Mooi. Tel: +31 30 2743091. Fax: +31 30 2744449. e-mail: fr.mooi{at}rivm.nl
In several countries pertussis is re-emerging, despite a high vaccination coverage. It is suggested that antigenic divergence between Bordetella pertussis vaccine strains and circulating strains, in particular with respect to pertactin, has contributed to pertussis re-emergence. Polymorphism in pertactin is essentially limited to region 1, which is composed of repeats and is located adjacent to an Arg-Gly-Asp motif implicated in adherence. Evidence is provided for the immunological relevance of polymorphism in region 1. Region 1 was found to contain a B-cell epitope recognized in both humans and mice. Furthermore, variation in region 1 affected antibody binding and, in a mouse respiratory infection model, the efficacy of a whole-cell vaccine. Moreover, passive and active immunization indicated that region 1 confers protective immunity. An mAb directed against a linear conserved epitope conferred cross-immunity against isolates with distinct pertactin variants. The results indicate an important role of region 1 of pertactin in immunity.
Keywords: antigenic variation, P.69/pertactin, immunization, protective immunity
Abbreviations: HRP, horseradish peroxidase; MBP, maltose-binding protein; WCV, whole-cell pertussis vaccine
The GenBank accession numbers for the sequences reported in this paper are AJ011015, AJ011016, AJ011091, AJ011092, AJ011093, AJ132095, AJ245927 and X54547.
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