Implications of differential age distribution of disease-associated meningococcal lineages for vaccine development.
New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and ≥25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.
Department of Zoology, University of Oxford, Oxford, United Kingdom carina.brehony@zoo.ox.ac.uk.
Carina
C
Brehony
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
Caroline L
CL
Trotter
Public Health England, London, United Kingdom.
Mary E
ME
Ramsay
Public Health England, London, United Kingdom.
Manosree
M
Chandra
Department of Zoology, University of Oxford, Oxford, United Kingdom.
Keith A
KA
Jolley
The Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Centre, Department of Medical Microbiology, Amsterdam, Netherlands.
Arie
A
van der Ende
Meningococcal Reference Laboratory, Scientific Institute of Public Health, Brussels, Belgium.
Françoise
F
Carion
Neisseria and Streptococcus Reference Laboratory, Statens Serum Institut, Copenhagen, Denmark.
Lene
L
Berthelsen
Neisseria and Streptococcus Reference Laboratory, Statens Serum Institut, Copenhagen, Denmark.
Steen
S
Hoffmann
Department of Microbiology, Landspitali University Hospital, Reykjavik, Iceland.
Hjördís
H
Harðardóttir
Meningococcal Reference Laboratory, Madrid, Spain.
Julio A
JA
Vazquez
Irish Meningococcal and Meningitis Reference Laboratory, Dublin, Ireland.
Karen
K
Murphy
National Institute for Health and Welfare, Helsinki, Finland.
Maija
M
Toropainen
Laboratory of Antimicrobial Resistance, Department of Infectious Diseases, National Institute of Health Dr. Ricardo Jorge, Lisbon, Portugal.
Manuela
M
Caniça
Laboratory of Antimicrobial Resistance, Department of Infectious Diseases, National Institute of Health Dr. Ricardo Jorge, Lisbon, Portugal.
Eugenia
E
Ferreira
The Scottish Haemophilus, Legionella, Meningococcus, and Pneumococcus Reference Laboratory, Glasgow, United Kingdom.
Mathew
M
Diggle
The Scottish Haemophilus, Legionella, Meningococcus, and Pneumococcus Reference Laboratory, Glasgow, United Kingdom.
Giles F
GF
Edwards
National Reference Centre for Meningococci, Pasteur Institute, Paris, France.
Muhamed-Kheir
MK
Taha
Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Paola
P
Stefanelli
National Reference Laboratory for Meningococcal Infections, National Institute of Public Health, Prague, Czech Republic.
Paula
P
Kriz
Meningococcal Reference Unit, Manchester Royal Infirmary, Manchester, United Kingdom.
Steve J
SJ
Gray
Meningococcal Reference Unit, Manchester Royal Infirmary, Manchester, United Kingdom.
Andrew J
AJ
Fox
National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
Susanne
S
Jacobsson
Institut für Hygiene und Mikrobiologie, Würzburg, Germany.
Heike
H
Claus
Institut für Hygiene und Mikrobiologie, Würzburg, Germany.
Ulrich
U
Vogel
National Meningococcal Reference Laboratory, National School of Public Health, Athens, Greece.
Georgina
G
Tzanakaki
National Reference Centre for Meningococci, Institute for Medical Microbiology and Hygiene, Graz, Austria.
Sigrid
S
Heuberger
Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Oslo, Norway.
Dominique A
DA
Caugant
Institut für Hygiene und Mikrobiologie, Würzburg, Germany.
Matthias
M
Frosch
Department of Zoology, University of Oxford, Oxford, United Kingdom.
Martin C J
MC
Maiden
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000942:Antigens, Bacterial / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology*; D058885:Multilocus Sequence Typing; D009345:Neisseria meningitidis / Q000276:immunology* / Q000302:isolation & purification; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D017422:Sequence Analysis, DNA; D055815:Young Adult
D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines; C039455:capsular polysaccharide, meningococcal group B