Prediction by genetic MATS of 4CMenB vaccine strain coverage of invasive meningococcal serogroup B isolates circulating in Taiwan between 2003 and 2020

Abstract

Neisseria meningitidis serogroup B (NmB) strains have diverse antigens, necessitating methods for predicting meningococcal serogroup B (MenB) vaccine strain coverage. The genetic Meningococcal Antigen Typing System (gMATS), a correlate of MATS estimates, predicts strain coverage by the 4-component MenB (4CMenB) vaccine in cultivable and non-cultivable NmB isolates. In Taiwan, 134 invasive, disease-causing NmB isolates were collected in 2003-2020 (23.1%, 4.5%, 5.2%, 29.8%, and 37.3% from individuals aged ≤11 months, 12-23 months, 2-4 years, 5-29 years, and ≥30 years, respectively). NmB isolates were characterized by whole-genome sequencing and vaccine antigen genotyping, and 4CMenB strain coverage was predicted using gMATS. Analysis of phylogenetic relationships with 502 global NmB genomes showed that most isolates belonged to three global hyperinvasive clonal complexes: ST-4821 (27.6%), ST-32 (23.9%), and ST-41/44 (14.9%). Predicted strain coverage by gMATS was 62.7%, with 27.6% isolates covered, 2.2% not covered, and 66.4% unpredictable by gMATS. Age group coverage point estimates ranged from 42.9% (2-4 years) to 66.1% (≤11 months). Antigen coverage estimates and percentages predicted as covered/not covered were highly variable, with higher estimates for isolates with one or more gMATS-positive antigens than for isolates positive for one 4CMenB antigen. In conclusion, this first study on NmB strain coverage by 4CMenB in Taiwan shows 62.7% coverage by gMATS, with predictable coverage for 29.8% of isolates. These could be underestimated since the gMATS calculation does not consider synergistic mechanisms associated with simultaneous antibody binding to multiple targets elicited by multicomponent vaccines or the contributions of minor outer membrane vesicle vaccine components.IMPORTANCEMeningococcal diseases, caused by the bacterium Neisseria meningitidis (meningococcus), include meningitis and septicemia. Although rare, invasive meningococcal disease is often severe and can be fatal. Nearly all cases are caused by six meningococcal serogroups (types), including meningococcal serogroup B. Vaccines are available against meningococcal serogroup B, but the antigens targeted by these vaccines have highly variable genetic features and expression levels, so the effectiveness of vaccination may vary depending on the strains circulating in particular countries. It is therefore important to test meningococcal serogroup B strains isolated from specific populations to estimate the percentage of bacterial strains that a vaccine can protect against (vaccine strain coverage). Meningococcal isolates were collected in Taiwan between 2003 and 2020, of which 134 were identified as serogroup B. We did further investigations on these isolates, including using a method (called gMATS) to predict vaccine strain coverage by the 4-component meningococcal serogroup B vaccine (4CMenB).

Keywords: 4CMenB; Taiwan; genetic Meningococcal Antigen Typing System; meningococcal disease; serogroup B; strain coverage.

Fig 1

Distribution of 134 NmB isolates by patient age group.

Fig 2

Phylogenetic distribution of clonal complexes of 134 NmB isolates from Taiwan in relation to 502 randomly selected NmB isolates genomes downloaded from PubMLST, as reconstructed in network created in SplitsTree using the NeighborNet algorithm based on single-nucleotide polymorphisms identified by kSNP algorithm.

Fig 3

gMATS-based coverage distribution of isolates by the number of 4CMenB vaccine antigens contained in isolate contributing to coverage. Overall, 27.6% of isolates were covered, 2.2% were not covered, and 66.4% were unpredictable by gMATS. 4CMenB, 4-component MenB vaccine; U, unpredictable by gMATS; NA, genotyping data not available.

Fig 4

gMATS-based coverage distribution of isolates by clonal complex. ST, sequence type.

Fig 5

gMATS-based coverage distribution of isolates for individual 4CMenB vaccine antigen variants or peptides by gMATS strain coverage overall. 4CMenB, 4-component MenB vaccine; NA, genotyping data not available.