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Infection and Immunity, October 2004, p. 5955-5962, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5955-5962.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Distribution of Surface Protein Variants among Hyperinvasive Meningococci: Implications for Vaccine Design

Rachel Urwin,1* Joanne E. Russell,1,2,{dagger} Emily A. L. Thompson,1 Edward C. Holmes,1 Ian M. Feavers,2 and Martin C. J. Maiden1

Department of Zoology University of Oxford, Oxford,1 Division of Bacteriology, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts United Kingdom2

Received 17 March 2004/ Returned for modification 29 April 2004/ Accepted 24 June 2004

The bacterium Neisseria meningitidis is a major cause of meningitis and septicemia worldwide. Outer membrane proteins (OMPs) are candidates in the search for comprehensive meningococcal vaccines; however, the formulation of OMP vaccines is complicated by antigenic diversity, which is generated by high levels of genetic reassortment and strong positive selection in the meningococcal antigen genes. The genetic and antigenic diversity of three OMPs (FetA, PorA, and PorB) among a global collection of meningococcal isolates representative of the major hyperinvasive clonal complexes was determined. There was evidence for antigenic structuring among the three OMPs that could not be explained purely by descent. These observations violated the predictions of the clonal and epidemic clonal models of population structure but were in concordance with models of strain structure which propose that host immunity selects for nonoverlapping antigen combinations. The patterns of antigenic variant combinations suggested that an OMP-based vaccine with as few as six PorA and five FetA variant sequences could generate homologous immune responses against all 78 isolates examined.

* Corresponding author. Mailing address: Peter Medawar Building, Department of Zoology, University of Oxford, South Parks Rd., Oxford OX1 3SY, United Kingdom. Phone: 44 (1865) 281300. Fax: 44 (1865) 281275. E-mail: rachel.urwin{at}zoo.ox.ac.uk.

Editor: J. N. Weiser

{dagger} Present address: Dept. of Medical Physiology, University Medical Center, 3584 CG Utrecht, The Netherlands.

Infection and Immunity, October 2004, p. 5955-5962, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5955-5962.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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