Molecular Targets in Meningococci: Efficient Routine Characterization and Optimal Outbreak Investigation in Conjunction with Routine Surveillance of the Meningococcal Group B Vaccine Candidate, fHBP

Abstract

ABSTRACT In 2007, recommendations were proposed for the molecular typing of meningococci. Multilocus sequence typing (MLST) was recommended to guide national and international disease management and facilitate studies of population biology and evolution. Sequencing of porA variable regions (VRs) 1 and 2 and the fetA VR was recommended for monitoring antigenic distribution and investigating potential outbreaks. porB characterization was recommended if further resolution was required. Several investigational “group B” meningococcal vaccines, including two in the advanced stages of development, incorporate factor H-binding protein (fHBP). The requirement for routine surveillance of fhbp places additional pressure on reference laboratories, both financially and in terms of labor. This study investigated the optimal and most efficient molecular typing schemes for (i) routine meningococcal characterization and (ii) the investigation of potential outbreaks, in conjunction with routine surveillance of fhbp. All invasive disease isolates received by the Health Protection Agency Meningococcal Reference Unit between July 2007 and June 2008 ( n = 613) were characterized in terms of capsular group, porA , fetA VR, fhbp , and sequence type (ST). Following capsular grouping and porA genosubtyping, several predominant capsular group- porA combinations were identified. The levels of additional resolution afforded by fetA and fhbp were comparable and partially complementary. fhbp constitutes an effective substitute for fetA as a routine marker of antigenic distribution, thereby reducing costs in conjunction with fhbp surveillance. MLST afforded markedly superior resolution overall and is the optimal scheme for investigating outbreaks in which (i) typing data are unavailable for the index case or (ii) the index case possesses a known, predominant capsular group- porA repertoire.