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Journal of Clinical Microbiology, November 2009, p. 3577-3585, Vol. 47, No. 11
0095-1137/09/$08.00+0     doi:10.1128/JCM.00936-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Characterization of fHbp, nhba (gna2132), nadA, porA, Sequence Type (ST), and Genomic Presence of IS1301 in Group B Meningococcal ST269 Clonal Complex Isolates from England and Wales{triangledown}

Jay Lucidarme,1* Maurizio Comanducci,2 Jamie Findlow,1 Stephen J. Gray,1 Edward B. Kaczmarski,1 Malcolm Guiver,1 Elisabeth Kugelberg,3 Pamela J. Vallely,4 Philipp Oster,2 Mariagrazia Pizza,2 Stefania Bambini,2 Alessandro Muzzi,2 Christoph M. Tang,3 and Ray Borrow1

Health Protection Agency, Manchester, United Kingdom,1 Novartis Vaccines, Sienna, Italy,2 Imperial College, London, United Kingdom,3 University of Manchester, Manchester, United Kingdom4

Received 12 May 2009/ Returned for modification 26 June 2009/ Accepted 14 August 2009

Highly effective glycoconjugate vaccines exist against four of the five major pathogenic groups of meningococci: A, C, W-135, and Y. An equivalent vaccine against group B meningococci (menB) has remained elusive due to the poorly immunogenic capsular polysaccharide. A promising alternative, the investigational recombinant menB (rMenB)- outer membrane vesicle (OMV) vaccine, contains fHBP, NHBA (previously GNA2132), NadA, and outer membrane vesicles (OMVs) from the New Zealand MeNZB vaccine. MenB currently accounts for 90% of meningococcal disease in England and Wales, where the multilocus sequence type (ST) 269 (ST269) clonal complex (cc269) has recently expanded to account for a third of menB cases. To assess the potential cc269 coverage of the rMenB-OMV vaccine, English and Welsh cc269 isolates from the past decade were genetically characterized with respect to fHBP, NHBA, and NadA. All of the isolates harbored fHbp and nhba alleles, while 98% of the cc269 isolates were devoid of nadA. Subvariant profiling of fHbp, nhba, and porA against STs revealed the presence of two broadly distinct and well-defined clusters of isolates, centered around ST269 and ST275, respectively. An additional molecular marker, insertion sequence IS1301, was found to be present in 100% and <2% of isolates of the respective clusters. On the basis of the genetic data, the potential rMenB-OMV coverage of cc269 in England and Wales is high (up to 100%) within both clusters. Expression studies and serum bactericidal antibody assays will serve to enhance predictions of coverage and will augment ongoing studies regarding the significance of IS1301 within the ST269 cluster.

* Corresponding author. Mailing address: Vaccine Evaluation Unit, Health Protection Agency, P.O. Box 209, Floor 2, Clinical Sciences Building 2, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WZ, United Kingdom. Phone: 44 (0)161 276 6791. Fax: 44 (0)161 276 6792. E-mail: jay.lucidarme{at}hpa.org.uk

{triangledown} Published ahead of print on 16 September 2009.

Journal of Clinical Microbiology, November 2009, p. 3577-3585, Vol. 47, No. 11
0095-1137/09/$08.00+0     doi:10.1128/JCM.00936-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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