title: Molecular epidemiology of meningococcal disease in England and Wales 1975-1995, before the introduction of serogroup C conjugate vaccines.
abstract: A comprehensive meningococcal vaccine is yet to be developed. In the absence of a vaccine that immunizes against the serogroup B capsular polysaccharide, this can only be achieved by targeting subcapsular antigens, and a number of outer-membrane proteins (OMPs) are under consideration as candidates. A major obstacle to the development of such a vaccine is the antigenic diversity of these OMPs, and obtaining population data that accurately identify and catalogue these variants is an important component of vaccine design. The recently proposed meningococcal molecular strain-typing scheme indexes the diversity of two OMPs, PorA and FetA, that are vaccine candidates, as well as the capsule and multilocus sequence type. This scheme was employed to survey 323 meningococci isolated from invasive disease in England and Wales from 1975 to 1995, before the introduction of meningococcal conjugated serogroup C polysaccharide vaccines in 1999. The eight-locus typing scheme provided high typeability (99.4 %) and discrimination (Simpson's diversity index 0.94-0.99). The data showed cycling of meningococcal genotypes and antigenic types in the absence of planned interventions. Notwithstanding high genetic and antigenic diversity, most of the isolates belonged to one of seven clonal complexes, with 11 predominant strain types. Combinations of PorA and FetA, chosen on the basis of their prevalence over time, generated vaccine recipes that included protein variants found in 80 % or more of the disease isolates for this time period. If adequate immune responses can be generated, these results suggest that control of meningococcal disease with relatively simple protein component vaccines may be possible.
authors: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts EN6 3QG, UK.|Peter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, OX1 3SY, UK.
authors: Joanne E
authors: JE
authors: Russell
authors: Department of Biology, Pennsylvania State University, University Park, PA 16802, USA.|Peter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, OX1 3SY, UK.
authors: Rachel
authors: R
authors: Urwin
authors: Meningococcal Reference Unit, Health Protection Agency, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WZ, UK.
authors: Stephen J
authors: SJ
authors: Gray
authors: Meningococcal Reference Unit, Health Protection Agency, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WZ, UK.
authors: Andrew J
authors: AJ
authors: Fox
authors: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts EN6 3QG, UK.
authors: Ian M
authors: IM
authors: Feavers
authors: Peter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, OX1 3SY, UK.
authors: Martin C J
authors: MCJ
authors: Maiden
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D015373:Bacterial Typing Techniques; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000235:genetics; D004739:England / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000382:microbiology*; D017720:Molecular Epidemiology; D009345:Neisseria meningitidis / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D011110:Polymorphism, Genetic; D018272:Porins / Q000235:genetics; D017422:Sequence Analysis, DNA; D014852:Wales / Q000453:epidemiology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D004269:DNA, Bacterial; C093120:FrpB protein, bacteria; D018272:Porins; C057699:porin protein, Neisseria