Browsing Miscellaneous by Issue Date
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Predicted coverage by 4CMenB vaccine against invasive meningococcal disease cases in the Netherlands.Neisseria meningitidis serogroup B is a major cause of invasive meningococcal disease in Europe. In the absence of a conjugate serogroup B vaccine, a subcapsular 4CMenB vaccine was developed. Data on 4CMenB vaccine efficacy is still limited. Recently, genomic MATS (Meningococcal Antigen Typing System) was developed as a tool to predict strain coverage, using vaccine antigens sequence data. We characterized all invasive meningococcal isolates received by the Netherlands Reference Laboratory for Bacterial Meningitis (NRLBM) in two epidemiological years 2017-2019 using whole-genome sequencing and determined serogroup, clonal complex (cc) and estimated 4CMenB vaccine coverage by gMATS. Of 396 cases of invasive meningococcal disease, corresponding to an incidence of 1.22 cases/105 inhabitants, 180 (45%) were serogroup W, 155 (39%) serogroup B, 46 (12%) serogroup Y, 10 (3%) serogroup C, 2 non-groupable (0.5%) and 3 (0.7%) unknown. The incidence was the highest among 0-4 years olds (4 cases/105 inhabitants), and 57/72 (79%) of these cases were serogroup B. Serogroup W predominated among persons 45 years of age or older with 110/187 (59%) cases. Serogroup B isolates comprised 11 different clonal complexes, with 103/122 (84%) isolates belonging to 4 clonal complexes: cc32, cc41/44, cc269 and cc213. In contrast, serogroup W isolates were genetically similar with 95% belonging to cc11. Of 122 serogroup B isolates, 89 (73%; 95% CI: 64-80%) were estimated to be covered by 4CMenB and the degree of coverage varied largely by clonal complex and age. Among the 0-4 year olds, 25 of 43 (58%; 95% CI: 43-72%) MenB isolates were estimated to be covered. Since the coverage of the 4CMenB vaccine is dependent on circulating clonal complexes, our findings emphasize the need for surveillance of circulating meningococcal strains. In addition, estimation of age specific coverage is relevant to determine the right target age group for vaccination.
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Enhanced Enterovirus D68 Replication in Neuroblastoma Cells Is Associated with a Cell Culture-Adaptive Amino Acid Substitution in VP1.Since its emergence in the United States in 2014, enterovirus D68 (EV-D68) has been and is associated with severe respiratory diseases and acute flaccid myelitis. Even though EV-D68 has been shown to replicate in different neuronal cells in vitro, it is currently poorly understood which viral factors contribute to the ability to replicate efficiently in cells of the central nervous system and whether this feature is a clade-specific feature. Here, we determined the replication kinetics of clinical EV-D68 isolates from (sub)clades A, B1, B2, B3, and D1 in human neuroblastoma cells (SK-N-SH). Subsequently, we compared sequences to identify viral factors associated with increased viral replication. All clinical isolates replicated in SK-N-SH cells, although there was a large difference in efficiency. Efficient replication of clinical isolates was associated with an amino acid substitution at position 271 of VP1 (E271K), which was acquired during virus propagation in vitro Recognition of heparan sulfate in addition to sialic acids was associated with increased attachment, infection, and replication. Removal of heparan sulfate resulted in a decrease in attachment, internalization, and replication of viruses with E271K. Taken together, our study suggests that the replication kinetics of EV-D68 isolates in SK-N-SH cells is not a clade-specific feature. However, recognition of heparan sulfate as an additional receptor had a large effect on phenotypic characteristics in vitro. These observations emphasize the need to compare sequences from virus stocks with clinical isolates in order to retrieve phenotypic characteristics from original virus isolates.IMPORTANCE Enterovirus D68 (EV-D68) causes mild to severe respiratory disease and is associated with acute flaccid myelitis since 2014. Currently, the understanding of the ability of EV-D68 to replicate in the central nervous system (CNS), and whether it is associated with a specific clade of EV-D68 viruses or specific viral factors, is lacking. Comparing different EV-D68 clades did not reveal clade-specific phenotypic characteristics. However, we did show that viruses which acquired a cell culture-adapted amino acid substitution in VP1 (E271K) recognized heparan sulfate as an additional receptor. Recognition of heparan sulfate resulted in an increase in attachment, infection, and replication in neuroblastoma cells compared with viruses without this specific amino acid substitution. The ability of EV-D68 viruses to acquire cell culture-adaptive substitutions which have a large effect in experimental settings emphasizes the need to sequence virus stocks.
