title: Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the United States.
abstract: Neisseria meningitidis (Nm) serogroups B, C and Y are the major causes of meningococcal diseases in the United States. NmB accounts for ∼1/3 of the disease but no licensed vaccine is yet available. Two candidate vaccines are being developed specifically to target NmB, but may also provide protection against other serogroups. To assess the potential impact of these vaccines on NmB and other serogroups causing disease in the US, we determined the prevalence, genetic diversity and epidemiological characteristics of three candidate antigen genes in Nm isolates collected through Active Bacterial Core surveillance (ABCs), a population-based active surveillance program. fHbp was detected in all NmB, NmY and NmW135 isolates. Eleven NmC isolates contain fHbp with a single base-pair deletion creating a frame shift in the C-terminal region. Among NmB, 59% were FHbp subfamily/variant B/v1 and 41% A/v2-3. Among NmC and NmY, 39% and 3% were B/v1, respectively. nadA was detected in 39% of NmB, 61% of NmC and 4% of NmY. Among isolates tested, nhbA was present in all NmB and 96% of non-B. For the subset of strains sequenced for NadA and NhbA, pairwise identity was greater than 93% and 78%, respectively. The proportion of FHbp subfamily/variant was different between ABCs site and year, but no linear temporal trend was observed. Although assessment of the vaccine coverage also requires understanding of the antigen expression and the ability to induce bactericidal activity, our finding that all isolates contain one or more antigen genes suggests these candidate vaccines may protect against multiple Nm serogroups.
authors.affiliation: Meningitis and Vaccine Preventable Disease Branch, Division of Bacterial Diseases, National Center of Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, United States. gqe8@cdc.gov
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Amanda
authors.initials: A
authors.lastname: Cohn
authors.forename: Maurizio
authors.initials: M
authors.lastname: Comanducci
authors.forename: Lubomira
authors.initials: L
authors.lastname: Andrew
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Jessica R
authors.initials: JR
authors.lastname: MacNeil
authors.forename: Susanna
authors.initials: S
authors.lastname: Schmink
authors.forename: Alessandro
authors.initials: A
authors.lastname: Muzzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Bambini
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Ellen
authors.initials: E
authors.lastname: Murphy
authors.forename: Susan K
authors.initials: SK
authors.lastname: Hoiseth
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.forename: Annaliesa S
authors.initials: AS
authors.lastname: Anderson
authors.forename: Lee H
authors.initials: LH
authors.lastname: Harrison
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Clark
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Messonnier
authors.forename: Leonard W
authors.initials: LW
authors.lastname: Mayer
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000382:microbiology*; D008875:Middle Aged; D017720:Molecular Epidemiology; D009345:Neisseria meningitidis / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D015995:Prevalence; D017384:Sequence Deletion; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C501982:NadA protein, Neisseria meningitidis; C484699:factor H-binding protein, Neisseria meningitidis