scholarly journals Determination of serotyping antigens, clonal analysis and genetic characterization of the 4CMenB vaccine antigen genes in invasive Neisseria meningitidis from Western Canada, 2009 to 2013

2014 ◽  
Vol 63 (11) ◽  
pp. 1490-1499 ◽  
Author(s):  
Dennis K. S. Law ◽  
Jianwei Zhou ◽  
Saul Deng ◽  
Linda Hoang ◽  
Gregory Tyrrell ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Clonal Complex ◽  
Factor H ◽  
Vaccine Antigen ◽  
Western Canada ◽  
Antigenic Analysis ◽  
Clonal Nature ◽  
4Cmenb Vaccine

This study examined invasive Neisseria meningitidis recovered from invasive meningococcal disease (IMD) cases in Western Canada between 2009 and 2013. A total of 161 isolates from individual IMD cases were analysed for serogroup, serotype, serosubtype, PorA genotype, multi-locus sequence type and nucleotide sequence of their 4CMenB vaccine antigen genes. Sixty-nine isolates were serogroup B (MenB), 47 were serogroup Y (MenY), 22 were serogroup C (MenC), 19 were serogroup W (MenW), three were serogroup E and one was non-encapsulated. MenC, MenY and MenW were mainly clonal, represented primarily by clonal complex (cc) 11, cc23 or cc167, and cc22, respectively. In contrast, MenB were composed of eight different ccs together with 11 isolates not assigned to any known cc. Antigenic analysis and PorA genotyping confirmed the heterogeneity of MenB isolates, while such results supported the clonal nature of most MenC, MenY and MenW isolates. Thirty-four (21.1 %) isolates had at least one gene that encoded one matching vaccine protein component of the 4CMenB vaccine (i.e. PorA P1.4; fHbp variant 1.1; NHBA peptide 2; and NadA-1, -2, or -3). An additional 18 isolates had genes that encoded variant 1 or subfamily B factor H binding proteins of this same vaccine.

scholarly journals Characterization of Neisseria meningitidis Isolates That Do Not Express the Virulence Factor and Vaccine Antigen Factor H Binding Protein

2011 ◽  
Vol 18 (6) ◽  
pp. 1002-1014 ◽  
Author(s):  
Jay Lucidarme ◽  
Lionel Tan ◽  
Rachel M. Exley ◽  
Jamie Findlow ◽  
Ray Borrow ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Binding Protein ◽  
Factor H ◽  
Negative Regulator ◽  
Vaccine Antigen ◽  
Natural Immunity ◽  
Content Type ◽  
Reading Frame ◽  
Flanking Sequences

ABSTRACTNeisseria meningitidisremains a leading cause of bacterial sepsis and meningitis. Complement is a key component of natural immunity against this important human pathogen, which has evolved multiple mechanisms to evade complement-mediated lysis. One approach adopted by the meningococcus is to recruit a human negative regulator of the complement system, factor H (fH), to its surface via a lipoprotein, factor H binding protein (fHbp). Additionally, fHbp is a key antigen in vaccines currently being evaluated in clinical trials. Here we characterize strains ofN. meningitidisfrom several distinct clonal complexes which do not express fHbp; all strains were recovered from patients with disseminated meningococcal disease. We demonstrate that these strains have either a frameshift mutation in thefHbpopen reading frame or have entirely lostfHbpand some flanking sequences. No fH binding was detected to other ligands among thefHbp-negative strains. The implications of these findings for meningococcal pathogenesis and prevention are discussed.

scholarly journals Whole genome sequencing of Neisseria meningitidis W isolates from the Czech Republic recovered in 1984 – 2017

2018 ◽  
Author(s):  
Michal Honskus ◽  
Zuzana Okonji ◽  
Martin Musilek ◽  
Jana Kozakova ◽  
Pavla Krizova
Keyword(s):  
Czech Republic ◽  
Neisseria Meningitidis ◽  
Clonal Complex ◽  
Vaccine Antigen ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
The Czech Republic ◽  
Vaccine Potential ◽  
Healthy Carriers

AbstractIntroductionThe study presents the analysis of whole genome sequence (WGS) data for Neisseria meningitidis serogroup W isolates recovered in the Czech Republic in 1984 – 2017 and their comparison with WGS data from other countries.Material and MethodsThirty-one Czech N. meningitidis W isolates, 22 from invasive meningococcal disease (IMD) and nine from healthy carriers were analysed. The 33-year study period was divided into three periods: 1984-1999, 2000-2009, and 2010-2017.ResultsMost study isolates from IMD and healthy carriers were assigned to clonal complex cc22 (n = 10) in all study periods. The second leading clonal complex was cc865 (n = 8) presented by IMD (n = 7) and carriage (n = 1) isolates that emerged in the last study period, 2010 – 2017. The third clonal complex was cc11 (n = 4) including IMD isolates from the first (1984 – 1999) and third (2010 – 2017) study periods. The following clonal complex was cc174 (n = 3) presented by IMD isolates from the first two study periods, i.e. 1984 – 1999 and 2000 – 2009. One isolate of each cc41/44 and cc1136 originated from healthy carriers from the second study period, 2000 - 2009. The comparison of WGS data for N. meningitidis W isolates recovered in the Czech Republic in the study period 1984 – 2017 and for isolates from other countries recovered in the same period showed that clonal complex cc865, ST-3342 is unique to the Czech Republic since 2010. Moreover, the comparison shows that cc11 in the Czech Republic does not comprise novel hypervirulent lineages reported from both European and non-European countries. WGS data for Czech serogroup W meningococci point to the presence of MenB vaccine antigen genes and confirm the hypothesis about the MenB vaccine potential against N. meningitidis serogroup W. All 31 study isolates were assigned to Bexsero® Antigen Sequence Types (BAST), and seven of them were of newly described BASTs.ConclusionsWGS analysis contributed considerably to a more detailed molecular characterization of N. meningitidis W isolates recovered in the Czech Republic over a 33-year period and allowed for a spatial and temporal comparison of these characteristics between isolates from the Czech Republic and other countries. In addition, the WGS data precised the base for the update of the recommendation for vaccination in the Czech Republic.

scholarly journals Full Molecular Typing of Neisseria meningitidis Directly from Clinical Specimens for Outbreak Investigation

2020 ◽  
Vol 58 (12) ◽  
Author(s):  
Mark Itsko ◽  
Adam C. Retchless ◽  
Sandeep J. Joseph ◽  
Abigail Norris Turner ◽  
Jose A. Bazan ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Molecular Typing ◽  
De Novo ◽  
Multiple Displacement Amplification ◽  
Low Cost ◽  
Vaccine Antigen ◽  
Content Type ◽  
Clinical Specimens ◽  
Low Culture

ABSTRACT Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis worldwide and an occasional cause of meningococcal urethritis. When isolates are unavailable for surveillance or outbreak investigations, molecular characterization of pathogens needs to be performed directly from clinical specimens, such as cerebrospinal fluid (CSF), blood, or urine. However, genome sequencing of specimens is challenging because of low bacterial and high human DNA abundances. We developed selective whole-genome amplification (SWGA), an isothermal multiple-displacement amplification-based method, to efficiently enrich, sequence, and de novo assemble N. meningitidis DNA from clinical specimens with low bacterial loads. SWGA was validated with 12 CSF specimens from invasive meningococcal disease cases and 12 urine specimens from meningococcal urethritis cases. SWGA increased the mean proportion of N. meningitidis reads by 2 to 3 orders of magnitude, enabling identification of at least 90% of the 1,605 N. meningitidis core genome loci for 50% of the specimens. The validated method was used to investigate two meningitis outbreaks recently reported in Togo and Burkina Faso. Twenty-seven specimens with low bacterial loads were processed by SWGA before sequencing, and 12 of 27 were successfully assembled to obtain the full molecular typing and vaccine antigen profile of the N. meningitidis pathogen, thus enabling thorough characterization of outbreaks. This method is particularly important for enhancing molecular surveillance in regions with low culture rates. SWGA produces enough reads for phylogenetic and allelic analysis at a low cost. More importantly, the procedure can be extended to enrich other important human bacterial pathogens.

Characterization of Neisseria meningitidis isolates collected from 1974 to 2003 in Japan by multilocus sequence typing

2004 ◽  
Vol 53 (7) ◽  
pp. 657-662 ◽  
Author(s):  
Hideyuki Takahashi ◽  
Toshiro Kuroki ◽  
Yuko Watanabe ◽  
Hiroshi Tanaka ◽  
Hiroo Inouye ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Neisseria Meningitidis ◽  
Multilocus Sequence Typing ◽  
Clonal Complex ◽  
The Other ◽  
Mlst Database ◽  
Mlst Analysis ◽  
The Past ◽  
Sequence Types

Analysis of 182 Neisseria meningitidis strains isolated over the past 30 years in Japan by serogroup typing and multilocus sequence typing (MLST) was performed. The serogroups of the 182 Japanese isolates were B (103 isolates), Y (39), W135 (1) and non-groupable (39). By MLST analysis, 65 different sequence types (ST) were identified, 42 of which were not found in the MLST database as of January 2004 and seemed to be unique to Japan. Statistical analysis of the MLST results revealed that, although the Japanese isolates seemed to be genetically divergent, they were classified into six major clonal complexes and other minor complexes. Among these isolates, well-documented ST complexes found worldwide were present, such as ST-23 complex (49 isolates), ST-44 complex (41 isolates) and ST-32 complex (8 isolates). On the other hand, a new clonal complex designated ST-2046 complex (28 isolates), which has not been identified in other countries, was also found, suggesting that this clone was indigenous to Japan. Taken together, it was speculated that meningococcal isolates in Japan comprised heterogeneous clones, which were derived both from clones identified in other countries and clones unique to Japan.

scholarly journals Characterization of InvasiveNeisseria meningitidisfrom Atlantic Canada, 2009 To 2013: With Special Reference to the Nonpolysaccharide Vaccine Targets (Pora, Factor H Binding Protein,NeisseriaHeparin-Binding Antigen andNeisseriaAdhesin A)

2015 ◽  
Vol 26 (6) ◽  
pp. 299-304 ◽  
Author(s):  
Raymond SW Tsang ◽  
Dennis KS Law ◽  
Rita R Gad ◽  
Tim Mailman ◽  
Gregory German ◽  
...  
Keyword(s):  
Clonal Analysis ◽  
Factor H ◽  
Vaccine Antigen ◽  
Atlantic Canada ◽  
Successful Implementation ◽  
Heparin Binding ◽  
Antigen Peptide ◽  
Genes Encoding ◽  
Adequate Coverage

BACKGROUND: Serogroup BNeisseria meningitidis(MenB) has always been a major cause of invasive meningococcal disease (IMD) in Canada. With the successful implementation of a meningitis C conjugate vaccine, the majority of IMD in Canada is now caused by MenB.OBJECTIVE: To investigate IMD case isolates in Atlantic Canada from 2009 to 2013. Data were analyzed to determine the potential coverage of the newly licensed MenB vaccine.METHODS: Serogroup, serotype and serosubtype antigens were determined from IMD case isolates. Clonal analysis was performed using multilocus sequence typing. The protein-based vaccine antigen genes were sequenced and the predicted peptides were investigated.RESULTS: The majority of the IMD isolates were MenB (82.5%, 33 of 40) and, in particular, sequence type (ST)-154 B:4:P1.4 was responsible for 47.5% (19 of 40) of all IMD case isolates in Atlantic Canada. Isolates of this clone expressed the PorA antigen P1.4 and possessed thenhbagenes encoding forNeisseriaheparin-binding antigen peptide 2, which together matched exactly with two of the four components of the new four-component meningococcal B vaccine. Nineteen MenB isolates had two antigenic matches, another five MenB and one meningitis Y isolate had one antigenic match. This provided 75.8% (25 of 33) potential coverage for MenB, or a 62.5% (25 of 40) overall potential coverage for IMD.CONCLUSION: From 2009 to 2013, IMD in Atlantic Canada was mainly caused by MenB and, in particular, the B:4:P1.4 ST-154 clone, which accounted for 47.5% of all IMD case isolates. The new four-component meningococcal B vaccine appeared to offer adequate coverage against MenB in Atlantic Canada.

scholarly journals Meningococcal B vaccine antigen FHbp variants among disease-causing Neisseria meningitidis B isolates, Italy, 2014–2017

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241793
Author(s):  
Anna Carannante ◽  
Cecilia Fazio ◽  
Arianna Neri ◽  
Florigio Lista ◽  
Silvia Fillo ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Vaccine Coverage ◽  
Factor H ◽  
Vaccine Antigen ◽  
Molecular Surveillance ◽  
Potential Vaccine ◽  
High Degree ◽  
Culture Positive ◽  
Culture Negative ◽  
National Surveillance System

Background Typing of Neisseria meningitidis isolates is crucial for the surveillance of invasive meningococcal disease (IMD). We performed a molecular epidemiology study of N. meningitidis serogroup B (MenB) causing IMD in Italy between 2014 and 2017 to describe circulating strains belonging to this serogroup, with particular regards to the two factor H-binding protein (FHbp) subfamilies present in the bivalent MenB vaccine. Materials and methods A total of 109 culture positive and 46 culture negative MenB samples were collected within the National Surveillance System (NSS) of IMD in Italy and molecularly analyzed by conventional methods. Results Overall, 71 MenB samples showed the FHbp subfamily A and 83 the subfamily B. The subfamily variants were differently distributed by age. The most frequent variants, A05 and B231, were associated with cc213 and cc162, respectively. All MenB with the FHbp A05 variant displayed the PorA P1.22,14 and 85.7% of them the FetA F5-5. The majority of MenB with the FHbp B231 variant showed the PorA P1.22,14 (65.4%) and 84.6%, the FetA F3-6. Conclusion MenB circulating in Italy were characterized by a remarkable association between clonal complex and FHbp variants, although a high degree of genetic diversity observed over time. A dynamic trend in clonal complexes distribution within MenB was detected. Our results stress the importance of continued meningococcal molecular surveillance to evaluate the potential vaccine coverage of the available MenB vaccines.

The vaccine antigen factor H binding protein from Neisseria meningitidis can be modified to reduce binding to factor H with no change in immunogenicity

2010 ◽  
Vol 61 (6) ◽  
pp. 516-517
Author(s):  
Lionel Tan ◽  
Joe Caesar ◽  
Yanwen Li ◽  
Rachel Exley ◽  
Elisabeth Kugelberg ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Binding Protein ◽  
Factor H ◽  
Vaccine Antigen

scholarly journals Culture-Confirmed Invasive Meningococcal Disease in Canada, 2010 to 2014: Characterization of Serogroup B Neisseria meningitidis Strains and Their Predicted Coverage by the 4CMenB Vaccine

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Raymond S. W. Tsang ◽  
Dennis K. S. Law ◽  
Rosita De Paola ◽  
Maria Giuliani ◽  
Maria Stella ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Neisseria Meningitidis ◽  
Meningococcal Disease ◽  
Factor H ◽  
Invasive Meningococcal Disease ◽  
Effective Control ◽  
Atlantic Region ◽  
Content Type ◽  
Laboratory Surveillance ◽  
4Cmenb Vaccine

ABSTRACT The molecular epidemiology of culture-confirmed invasive meningococcal disease (IMD) in Canada from 2010 to 2014 was studied with an emphasis on serogroup B Neisseria meningitidis (MenB) isolates, including their predicted coverage by the 4CMenB vaccine. The mean annual incidence rates of culture confirmed IMD varied from 0.19/100,000 in Ontario to 0.50/100,000 in New Brunswick and 0.59/100,000 in Quebec. In both Quebec and Atlantic region, MenB was significantly more common than other serogroups, while in other provinces, both MenB and serogroup Y (MenY) were almost equally common. The majority of MenB cases (67.0%) were in those aged ≤24 years, while most MenC (75.0%) and MenY (69.6%) cases were in adults more than 24 years old. The 349 MenB isolates were grouped into 103 sequence types (STs), 90 of which belonged to 13 clonal complexes (CCs). A large number of 4CMenB antigen genes were found among the Canadian MenB, which is predicted to encode 50 factor H binding protein (fHbp) types, 40 NHBA types, and 55 PorA genotypes. Provinces and regions were found to have their own unique MenB STs. A meningococcal antigen typing system assay predicted an overall MenB coverage by 4CMenB to be 73.6%, with higher coverage predicted for the two most common STs: 100% for ST154 and 95.9% for ST269, leading to higher coverage in both the Atlantic region and Quebec. Higher coverage (81.4%) was also found for MenB recovered from persons aged 15 to 24 years, followed by strains from infants and children ≤4 years old (75.2%) and those aged 5 to 14 years (75.0%). IMPORTANCE Laboratory surveillance of invasive meningococcal disease (IMD) is important to our understanding of the evolving nature of the Neisseria meningitidis strain types causing the disease and the potential coverage of disease strains by the newly developed vaccines. This study examined the molecular epidemiology of culture-confirmed IMD cases in Canada by examining the strain types and the potential coverage of a newly licensed 4CMenB vaccine on Canadian serogroup B N. meningitidis strains. The strain types identified in different parts of Canada appeared to be unique as well as their predicted coverage by the 4CMenB vaccine. These data were compared to data obtained from previous studies done in Canada and elsewhere globally. For effective control of IMD, laboratory surveillance of this type was found to be essential and useful to understand the dynamic nature of this disease.

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