title: Predicted Strain Coverage of a New Meningococcal Multicomponent Vaccine (4CMenB) in Spain: Analysis of the Differences with Other European Countries.
abstract: BACKGROUND
  A novel meningococcal multicomponent vaccine, 4CMenB (Bexsero®), has been approved in Europe, Canada, Australia and US. The potential impact of 4CMenB on strain coverage is being estimated by using Meningococcal Antigen Typing System (MATS), an ELISA assay which measures vaccine antigen expression and diversity in each strain. Here we show the genetic characterization and the 4CMenB potential coverage of Spanish invasive strains (collected during one epidemiological year) compared to other European countries and discuss the potential reasons for the lower estimate of coverage in Spain.
  
  
  METHODS
  A panel of 300 strains, a representative sample of all serogroup B Neisseria meningitidis notified cases in Spain from 2009 to 2010, was characterized by multilocus sequence typing (MLST) and FetA variable region determination. 4CMenB vaccine antigens, PorA, factor H binding protein (fHbp), Neisseria Heparin Binding Antigen (NHBA) and Neisserial adhesin A (NadA) were molecularly typed by sequencing. PorA coverage was assigned to strain with VR2 = 4. The levels of expression and cross-reactivity of fHbp, NHBA and NadA were analyzed using MATS ELISA.
  
  
  RESULTS
  Global estimated strain coverage by MATS was 68.67% (95% CI: 47.77-84.59%), with 51.33%, 15.33% and 2% of strains covered by one, two and three vaccine antigens, respectively. The predicted strain coverage by individual antigens was: 42% NHBA, 36.33% fHbp, 8.33% PorA and 1.33% NadA. Coverage within the most prevalent clonal complexes (cc) was 70.37% for cc 269, 30.19% for cc 213 and 95.83% for cc 32.
  
  
  CONCLUSIONS
  Clonal complexes (cc) distribution accounts for variations in strain coverage, so that country-by-country investigations of strain coverage and cc prevalence are important. Because the cc distribution could also vary over time, which in turn could lead to changes in strain coverage, continuous detailed surveillance and monitoring of vaccine antigens expression is needed in those countries where the multicomponent vaccine is introduced. This is really important in countries like Spain where most of the strains are predicted to be covered by only one vaccine antigen and the chance for escape mutants to emerge with vaccine use is higher. Based on the observed data, cc213 should receive special attention as it is associated with low predicted strain coverage, and has recently emerged in Spain.
authors.affiliation: Reference Laboratory for Meningococci, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Abad
authors.affiliation: Reference Laboratory for Meningococci, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Medina
authors.affiliation: Novartis Vaccines and diagnostics, a GSK Company, Siena, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Stella
authors.affiliation: Novartis Vaccines and diagnostics, a GSK Company, Siena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boccadifuoco
authors.affiliation: Novartis Vaccines and diagnostics, a GSK Company, Siena, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Comanducci
authors.affiliation: Novartis Vaccines and diagnostics, a GSK Company, Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bambini
authors.affiliation: Novartis Vaccines and diagnostics, a GSK Company, Siena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Muzzi
authors.affiliation: Reference Laboratory for Meningococci, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Vázquez
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D006801:Humans; D022401:Meningococcal Vaccines / Q000276:immunology*; D058889:Molecular Typing; D009345:Neisseria meningitidis / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D013030:Spain; D013045:Species Specificity
chemical_list: C570015:4CMenB vaccine; D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines