title: Comparison of Phenotypic and Genotypic Approaches to Capsule Typing of Neisseria meningitidis by Use of Invasive and Carriage Isolate Collections.
abstract: Neisseria meningitidis serogroup B (MnB) is a leading cause of bacterial meningitis; however, MnB is most commonly associated with asymptomatic carriage in the nasopharyngeal cavity, as opposed to the disease state. Two vaccines are now licensed for the prevention of MnB disease; a possible additional benefit of these vaccines could be to protect against disease indirectly by disrupting nasopharyngeal carriage (e.g., herd protection). To investigate this possibility, accurate diagnostic approaches to characterize MnB carriage isolates are required. In contrast to invasive meningococcal disease (IMD) isolates, which can be readily serogrouped, carriage isolates often lack capsule expression, making standard phenotypic assays unsuitable for strain characterization. Several antibody-based methods were evaluated for their abilities to serogroup isolates and were compared with two genotyping methods (real-time PCR [rt-PCR] and whole-genome sequencing [WGS]) to identify which approach would most accurately ascertain the polysaccharide groups associated with carriage isolates. WGS and rt-PCR were in agreement for 99% of IMD isolates, including those with coding sequences for MnB, MnC, MnW, and MnY, and the phenotypic methods correctly identified serogroups for 69 to 98% of IMD isolates. In contrast, only 47% of carriage isolates were groupable by genotypic methods, due to mutations within the capsule operon; of the isolates identified by genotypic methods, ≤43% were serogroupable with any of the phenotypic methods tested. These observations highlight the difficulties in the serogrouping and capsular genogrouping of meningococcal carriage isolates. Based on our findings, WGS is the most suitable approach for the characterization of meningococcal carriage isolates.
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA hal.jones@pfizer.com.
authors: C Hal
authors: CH
authors: Jones
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Naglaa
authors: N
authors: Mohamed
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Eduardo
authors: E
authors: Rojas
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Lubomira
authors: L
authors: Andrew
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Johanna
authors: J
authors: Hoyos
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Julio C
authors: JC
authors: Hawkins
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Lisa K
authors: LK
authors: McNeil
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Qin
authors: Q
authors: Jiang
authors: Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Leonard W
authors: LW
authors: Mayer
authors: Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Xin
authors: X
authors: Wang
authors: Institut National de Santé Publique du Québec, Quebec City, Canada Laval University, Quebec City, Canada CHU de Québec, Quebec City, Canada.
authors: Rodica
authors: R
authors: Gilca
authors: Institut National de Santé Publique du Québec, Quebec City, Canada Laval University, Quebec City, Canada CHU de Québec, Quebec City, Canada.
authors: Philippe
authors: P
authors: De Wals
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Louise
authors: L
authors: Pedneault
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Joseph
authors: J
authors: Eiden
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Kathrin U
authors: KU
authors: Jansen
authors: Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors: Annaliesa S
authors: AS
authors: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D016667:Bacterial Capsules / Q000145:classification* / Q000235:genetics / Q000276:immunology; D002353:Carrier State / Q000382:microbiology*; D016021:Epidemiologic Studies; D005260:Female; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D008297:Male; D009345:Neisseria meningitidis / Q000145:classification* / Q000235:genetics / Q000276:immunology; D016870:Neisseriaceae Infections / Q000382:microbiology*; D012703:Serotyping / Q000379:methods*; D055815:Young Adult