Abstract
In September 2015, 4CMenB meningococcal vaccine was introduced into the United Kingdom infant immunization program without phase 3 trial information. Understanding the effect of this program requires enhanced surveillance of invasive meningococcal disease (IMD) Neisseria meningitidis isolates and comparison with prevaccination isolates. Bexsero Antigen Sequence Types (BASTs) were used to analyze whole-genome sequences of 3,073 prevaccine IMD N. meningitidis isolates obtained during 2010−2016. Isolates exhibited 803 BASTs among 31 clonal complexes. Frequencies of antigen peptide variants were factor H binding protein 1, 13.4%; Neisserial heparin-binding antigen 2, 13.8%; Neisseria adhesin A 8, 0.8%; and Porin A-VR2:P1.4,10.9%. In 2015−16, serogroup B isolates showed the highest proportion (35.7%) of exact matches to >1 Bexsero components. Serogroup W isolates showed the highest proportion (93.9%) of putatively cross-reactive variants of Bexsero antigens. Results highlighted the likely role of cross-reactive antigens. BAST surveillance of meningococcal whole-genome sequence data is rapid, scalable, and portable and enables international comparisons of isolates.
Highlights
Neisseria meningitidis is an accidental human pathogen that is carried asymptomatically in the nasopharynx of 1%–40% of the population, depending on age and social behavior [1,2]
We found variation in clonal complex (CC) distribution over the 6-year period, with a 10-fold increase in CC11 and decreases in CC41/44 (172 to 56, 50.0%) and CC269 (108 to 52, 51.8%), which accounted for most serogroup B isolates (Figure 1)
The requirement for vaccines to protect against serogroup B meningococci from multiple CCs led to development of multipeptide vaccines, such as 4CMenB (Bexsero) and bivalent rLP2086 (Trumenba) [16,17]
Summary
Neisseria meningitidis is an accidental human pathogen that is carried asymptomatically in the nasopharynx of 1%–40% of the population, depending on age and social behavior [1,2]. The first serogroup B vaccines were derived from outer membrane vesicles (OMVs) for use in epidemics caused by single strains defined by genotype and Porin A (PorA) type [7]. The United Kingdom has low-incidence endemic disease and periods of hyperendemicity, which changes with frequency of hyperinvasive bacterial genotypes [10]. In the 1990s, hyperendemic serogroup C IMD caused by CC11 (C:CC11) prompted introduction of infant meningococcal C conjugate vaccination and a catch-up campaign, which reduced disease incidence and carriage of C:CC11 [11]. These candidates are composed of subcapsular proteins prevalent among many N. meningitidis strains. Their protective potential has been complicated by meningococcal diversity [13,14,15]. The rLP2086 vaccine contains 2 fHbp variants, 1 each from subfamily A (A05) and subfamily B (B01) [17]
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