Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the United States

Vaccine. 2011 Jun 24;29(29-30):4739-44. doi: 10.1016/j.vaccine.2011.04.092. Epub 2011 May 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Bacterial / genetics*
  • Bacterial Proteins / genetics
  • Child
  • Child, Preschool
  • Female
  • Frameshift Mutation
  • Genetic Variation*
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Meningococcal Infections / epidemiology*
  • Meningococcal Infections / microbiology*
  • Middle Aged
  • Molecular Epidemiology
  • Neisseria meningitidis / classification*
  • Neisseria meningitidis / genetics*
  • Neisseria meningitidis / isolation & purification
  • Prevalence
  • Sequence Deletion
  • United States / epidemiology
  • Young Adult

Substances

  • Adhesins, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • NadA protein, Neisseria meningitidis
  • factor H-binding protein, Neisseria meningitidis