Population Structure and Capsular Switching of InvasiveNeisseria meningitidisIsolates in the Pre–Meningococcal Conjugate Vaccine Era—United States, 2000–2005

Abstract

Background A quadrivalent meningococcal conjugate vaccine (MCV4) was licensed in the United States in 2005; no serogroup B vaccine is available. Neisseria meningitidis changes its capsular phenotype through capsular switching, which has implications for vaccines that do not protect against all serogroups. Methods Meningococcal isolates from 10 Active Bacterial Core Surveillance sites from 2000–2005 were analyzed so that changes following MCV4 licensure can be identified. Isolates were characterized by multilocus sequence typing (MLST) and outer membrane protein gene sequencing. Isolates expressing capsular polysaccharide different from that associated with the MLST lineage were considered to demonstrate capsule switching. Results Among 1,160 isolates, the most common genetic lineages were the ST-23, ST-32, ST-11, and ST-41/44 clonal complexes. Of serogroup B and Y isolates, 8 (1.5%) and 3 (0.9%), respectively, demonstrated capsular switching, compared to 36 (12.9%) for serogroup C (p <0.0001); most serogroup C switches were from virulent serogroup B and/or serogroup Y lineages. Conclusions A limited number of genetic lineages caused the majority of invasive meningococcal infections. A substantial proportion of isolates had evidence of capsular switching. The high prevalence of capsular switching requires surveillance to detect changes in meningococcal population structure that may impact effectiveness of meningococcal vaccines.

Significance of Meningococcal Hyperinvasive Clonal Complexes and Their Influence on Vaccines Development

“…The first report of epidemic potential of ST-32CC came from Norway, from 1969. Then its spread throughout European countries, South Africa and the Americas was observed (Harrison et al, 2009;Harrison et al, 2010;Racloz and Luiz, 2010). According to the MLST database and phenotyping analysis, three epidemic clones were characterized.…”

Controlling serogroup B invasive meningococcal disease: the Canadian perspective

“…When vaccines targeting some, but not all, capsular serogroups of meningococcci are used in a population, the vaccine-induced immunity may theoretically impose a selection pressure on the meningococcal population, potentially favoring capsule switching [25][26][27] and replacement [28,29]. Capsule switching occurs when vaccine strains (i.e., strains with capsule types included in the vaccine) acquire alternate capsular poly saccharide synthesis genes from nonvaccine strains (i.e., strains with capsule types not found in the vaccine) to become resistant to vaccine-induced host immunity.…”

“…Shortly after the ET-15 clone was identified as a cause of MenC outbreaks in Ontario [34], this strain quickly spread across the country [35,36] to the USA [37] and globally [38]. The confinement of MenB disease due to a single clone within a specific jurisdiction has also been seen in Oregon, USA due to the ET-5 (cc32) clone [26]. The apparent difference in the epidemiology of IMD due to the hyperinvasive serogroup B cc32 or cc269 clones and the MenC ET-15 clone is still not understood.…”

Meningococcal serogroup Y emergence in Europe

“…Michael Bröker, 1, * Susanne Jacobsson, 2 Markku Kuusi, 3 David Pace, 4 Maria J. Simões, 5 Anna Skoczynska, 6 Muhamed-Kheir Taha, 7 Maija Toropainen 3 and Georgina Tzanakaki Laboratory, National School of Public Health; Athens, Greece distribution of disease-causing serogroups vary over time and geographical location. [3][4][5] Although disease caused by serogroup X has been documented in Africa, it is not a common cause of IMD in other parts of the world.…”

“…[3][4][5] Although disease caused by serogroup X has been documented in Africa, it is not a common cause of IMD in other parts of the world. 6 Worldwide, over 90% of IMD is caused by serogroups A, B, C, Y and W-135.…”