Статті в журналах: "Neisseri meningitidis serogroup B"

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Kepenekli Kadayifci, Eda, Deniz Güneşer Merdan, Ahmet Soysal, Ayşe Karaaslan, Serkan Atıcı, Rıza Durmaz, Perran Boran, İhsan Turan, Güner Söyletir, and Mustafa Bakır. "Prevalence of Neisseria meningitidis carriage: a small-scale survey in Istanbul, Turkey." Journal of Infection in Developing Countries 10, no. 04 (April 28, 2016): 413–17. http://dx.doi.org/10.3855/jidc.7483.

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Introduction: The human nasopharynx is the main reservoir of Neisseria meningitidis, and asymptomatic carriage is common. N. meningitidis one of the common causes of bacterial meningitis in Turkey, especially after the implementation of the national immunization program that includes conjugated pneumococcal and Haemophilus influenzae type b vaccines. The purpose of this study was to evaluate the prevalence of meningococcal carriage and determine the leading serogroup, which may help authorities to adapt appropriate meningococal vaccine into the national immunization programme. Methodology: The prevalence of oropharyngeal carriage of N. meningitidis in 1,000 healthy subjects, 0–79 years of age, was investigated. Oropharyngeal swabs were collected during an 18-month period. Samples obtained were inoculated onto Thayer-Martin agar. The API-NH test and VITEK-MS system were used for identification of colonies. Multiplex real-time polymerase chain reaction assay was used to determine serogroups with serogroup-specific genes. Results: N. meningitidis was isolated from 6 of 1,000 subjects (0.6%). Meningoccocal carriers were between 21 and 40 years of age. All isolates were serogrouped as B, except one that did not survive on subculture. N. lactamica was isolated from 13 of 1,000 subjects (1.3%). Conclusions: Carriage rate of meningococci in our study was relatively low. However, we detected that serogroup B was the leading strain in meningococcal carriage in Istanbul; choosing an appropriate meningococcal vaccine containing serogroup B should therefore be considered. High absolute humidity throughout the year in Istanbul may explain the low prevalence of carriage in our study. This should be verified with a multicenter national survey.

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HILSE, R., J. STOEVESANDT, D. A. CAUGANT, H. CLAUS, M. FROSCH, and U. VOGEL. "Distribution of the meningococcal insertion sequence IS1301 in clonal lineages of Neisseria meningitidis." Epidemiology and Infection 124, no. 2 (April 2000): 337–40. http://dx.doi.org/10.1017/s0950268899003647.

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The distribution of the meningococcal insertion sequence IS1301 was analysed in 496 strains of different serogroups and clonal lineages of Neisseria meningitidis, and in 64 neisserial strains other than N. meningitidis. IS1301 was found in meningococci, but not in apathogenic Neisseria sp. and Neisseria gonorrhoeae. The copy numbers of IS1301 varied between 2 and 17 per genome. IS1301 positive strains were mostly found among the serogroups 29E, W135, X, and Y. Clonal lineages of serogroup A, B, and C meningococci associated with epidemic meningococcal disease were rarely positive for IS1301.

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Kourna Hama, Mamadou, Dam Khan, Boubou Laouali, Catherine Okoi, Abdoulaye Yam, Moussa Haladou, Archibald Worwui, et al. "Pediatric Bacterial Meningitis Surveillance in Niger: Increased Importance of Neisseria meningitidis Serogroup C, and a Decrease in Streptococcus pneumoniae Following 13-Valent Pneumococcal Conjugate Vaccine Introduction." Clinical Infectious Diseases 69, Supplement_2 (September 5, 2019): S133—S139. http://dx.doi.org/10.1093/cid/ciz598.

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Abstract Background Meningitis is endemic in Niger. Haemophilus influenzae type b (Hib) vaccine and the 13-valent pneumococcal conjugate vaccine (PCV13) were introduced in 2008 and 2014, respectively. Vaccination campaign against Neisseria meningitidis serogroup A was carried out in 2010–2011. We evaluated changes in pathogen distribution using data from hospital-based surveillance in Niger from 2010 through 2016. Methods Cerebrospinal fluid (CSF) specimens from children <5 years old with suspected meningitis were tested to detect vaccine-preventable bacterial pathogens. Confirmatory identification and serotyping/grouping of Streptococcus pneumoniae, N. meningitidis, and H. influenzae were done. Antimicrobial susceptibility testing and whole genome sequencing were performed on S. pneumoniae isolates. Results The surveillance included 2580 patients with suspected meningitis, of whom 80.8% (2085/2580) had CSF collected. Bacterial meningitis was confirmed in 273 patients: 48% (131/273) was N. meningitidis, 45% (123/273) S. pneumoniae, and 7% (19/273) H. influenzae. Streptococcus pneumoniae meningitis decreased from 34 in 2014, to 16 in 2016. PCV13 serotypes made up 88% (7/8) of S. pneumoniae meningitis prevaccination and 20% (5/20) postvaccination. Neisseria meningitidis serogroup C (NmC) was responsible for 59% (10/17) of serogrouped N. meningitidis meningitis. Hib caused 67% (2/3) of the H. influenzae meningitis isolates serotyped. Penicillin resistance was found in 16% (4/25) of S. pneumoniae isolates. Sequence type 217 was the most common lineage among S. pneumoniae isolates. Conclusions Neisseria meningitidis and S. pneumoniae remain important causes of meningitis in children in Niger. The decline in the numbers of S. pneumoniae meningitis post-PCV13 is encouraging and should continue to be monitored. NmC is the predominant serogroup causing N. meningitidis meningitis.

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Wang, Quan, Zhujun Shao, Xiaoting Wang, Yuan Gao, Machao Li, Li Xu, Jianguo Xu, and Lei Wang. "Genetic Study of Capsular Switching between Neisseria meningitidis Sequence Type 7 Serogroup A and C Strains." Infection and Immunity 78, no. 9 (July 12, 2010): 3883–88. http://dx.doi.org/10.1128/iai.00363-10.

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ABSTRACT Neisseria meningitidis is a leading cause of septicemia and meningitis worldwide. N. meningitidis capsular polysaccharides have been classified into 13 distinct serogroups which are defined by antibody reactivity and structural analysis, and the capsule plays an important role in virulence. Serogroups A, B, C, W135, and Y have been reported to be clinically important. Several newly identified serogroup C isolates belonging to the unique sequence type 7 (ST-7) were identified in China. Since most ST-7 isolates from China belonged to serogroup A, the newly identified ST-7 serogroup C strains were proposed to have arisen from those belonging to ST-7 serogroup A. In this study, six ST-7 serogroup C and three ST-7 serogroup A isolates were analyzed by pulsed-field gel electrophoresis to confirm their sequence type. In order to clarify the genetic basis of capsular switching between ST-7 serogroup A and C strains, the whole capsular gene clusters and surrounding genes of the two representative ST-7 strains belonging to serogroups A and C, respectively, were sequenced and compared. Potential recombination sites were analyzed using the RDP3 beta software, and recombination-related regions in two other ST-7 serogroup A and five ST-7 serogroup C strains were also sequenced and compared to the representative ST-7 serogroup A and C strain sequences.

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Abady, N. R., C. J. D. Guglielmino, R. M. Graham, J. Adelskov, H. V. Smith, B. K. C. Patel, and A. V. Jennison. "Genetic characterization of a Neisseria meningitidis cluster in Queensland, Australia." Canadian Journal of Microbiology 63, no. 7 (July 2017): 644–47. http://dx.doi.org/10.1139/cjm-2017-0017.

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Neisseria meningitidis serogroups B and C have been responsible for the majority of invasive meningococcal disease in Australia, with serogroup B strains causing an increasing proportion of cases in recent years. Serogroup Y has typically caused sporadic disease in Australia. In 2002, a cluster of 4 cases was reported from a rural region in Queensland. Three of these cases were serogroup C, with 1 case diagnosed by molecular detection only, and the fourth case was identified as a serogroup Y infection. Genomic analysis, including antigen finetyping, multilocus sequence typing (MLST), and core genome MLST, demonstrated that the serogroup Y case, though spatially and temporally linked to a serogroup C disease cluster, was not the product of a capsule switch and that one of the serogroup C isolates had a deletion of the entire porA sequence.

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Li, Yanwen, Yao-hui Sun, Cathy Ison, Myron M. Levine, and Christoph M. Tang. "Vaccination with Attenuated Neisseria meningitidis Strains Protects against Challenge with Live Meningococci." Infection and Immunity 72, no. 1 (January 2004): 345–51. http://dx.doi.org/10.1128/iai.72.1.345-351.2004.

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ABSTRACT Meningococcal disease is a life-threatening infection caused by Neisseria meningitidis. Currently, there are no vaccines to prevent infection with serogroup B N. meningitidis strains, the leading cause of meningococcal meningitis in Europe and North America. Here we describe the construction and characterization of two attenuated serogroup B N. meningitidis strains, YH102 (MC58Δsia ΔrfaF) and YH103 (MC58Δsia ΔmetH). Both strains are markedly attenuated in their capacity to cause bacteremia in rodent models and have a reduced ability to survive in a human whole-blood assay. Immunization of adult mice with these strains leads to the development of bactericidal antibodies and confers sterilizing protection against challenge with homologous live bacteria. Furthermore, we show that the strains confer protection against infection by other serogroups. Use of the attenuated strains in animals with gene knockouts or after depletion of immunological effectors could be used to define the basis of protection, and human volunteer studies could be undertaken to examine the immune response following exposure to this important human pathogen.

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Stabler, Richard A., Gemma L. Marsden, Adam A. Witney, Yanwen Li, Stephen D. Bentley, Christoph M. Tang, and Jason Hinds. "Identification of pathogen-specific genes through microarray analysis of pathogenic and commensal Neisseria species." Microbiology 151, no. 9 (September 1, 2005): 2907–22. http://dx.doi.org/10.1099/mic.0.28099-0.

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The release of the complete genome sequences of Neisseria meningitidis MC58 and Z2491 along with access to the sequences of N. meningitidis FAM18 and Neisseria gonorrhoeae FA1090 allowed the construction of a pan-Neisseria microarray, with every gene in all four genomes represented. The microarray was used to analyse a selection of strains including all N. meningitidis serogroups and commensal Neisseria species. For each strain, genes were defined as present, divergent or absent using gack analysis software. Comparison of the strains identified genes that were conserved within N. meningitidis serogroup B strains but absent from all commensal strains tested, consisting of mainly virulence-associated genes and transmissible elements. The microarray was able to distinguish between pilin genes, pilC orthologues and serogroup-specific capsule biosynthetic genes, and to identify dam and drg genotypes. Previously described N. meningitidis genes involved in iron response, adherence to epithelial cells, and pathogenicity were compared to the microarray analysis. The microarray data correlated with other genetic typing methods and were able to predict genotypes for uncharacterized strains and thus offer the potential for a rapid typing method. The subset of pathogen-specific genes identified represents potential drug or vaccine targets that would not eliminate commensal neisseriae and the associated naturally acquired immunity.

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Portilho, Amanda Izeli, Gabriela Trzewikoswki de Lima, and Elizabeth De Gaspari. "Neisseria meningitidis: analysis of pili and LPS in emerging Brazilian strains." Therapeutic Advances in Vaccines and Immunotherapy 8 (January 2020): 251513552091919. http://dx.doi.org/10.1177/2515135520919195.

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Background: Neisseria meningitidis is the main cause of bacterial meningitis in Brazil, where the main serogroups isolated are B and C; however, the serogroup W has recently emerged. LPS and type IV pili are important virulence factors that increase meningococci pathogenicity. Methods: The characterization of Lipopolysaccharide (LPS) and type IV pili in 19 meningococci strains of serogroup B, 21 of serogroup C, 45 of serogroup W and 28 of serogroup Y, isolated in Brazil between 2011 and 2017, was conducted using the Enzyme-linked Immunosorbent Assay (Dot- ELISA) technique and monoclonal antibodies. Results: We would like to emphasize the importance of characterizing relevant antigens, such as pili and LPS, the use of monoclonal antibodies to support it, and how such studies improve vaccine development and monitoring. Most of the strains studied presented L3,7,9 LPS and type IV pili; both antigens are associated with the capacity to cause invasive disease. Conclusion: Due to the impact of meningococcal disease, it is important to maintain and improve vaccine studies. Epitopes characterization provides data about the virulence of circulating strains. The use of monoclonal antibodies and serological techniques are relevant and support vaccine development.

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Ceyhan, Mehmet, Yasemin Ozsurekci, Cihangül Bayhan, Nezahat Gurler, Enes Sali, Melike Keser Emiroglu, Fatma Nur Öz, et al. "682. The Changing Epidemiology of Bacterial Meningitis During 2015–2017 in Turkey: A Hospital-Based Prospective Surveillance Study." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S246. http://dx.doi.org/10.1093/ofid/ofy210.689.

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Abstract Background The etiology of bacterial meningitis in Turkey has been changed after the implementation of conjugated vaccines against Streptococcus pneumonia and Haemophilus influenzae type b (Hib) in Turkish national immunization schedule. Methods. This prospective study was conducted in 25 hospitals located seven regions of Turkey (representing 30% of Turkey population) and children aged between 1 month and 18 years with suspected meningitis and hospitalized were included. Cerebrospinal fluid samples were collected and bacterial identification was made according to the multiplex PCR assay results. Results. During the study period, 927 children were hospitalized for suspected meningitis and Hib (n:1), S. pneumonia (n:17) and Neisseria meningitidis (n:59) were detected in 77 samples (Figure 1, Table 1). During 2015–2016, N. meningitidis serogroup W, B, A, Y, X frequencies were as 5 (13.9%), 16 (44.4%), 1 (2.8%), 1 (2.8%), 1 (2.8%), respectively. There were 12 nongroupable N. meningitidis samples and serogroup C was not detected. In 2017, of meningococcal meningitis serogroup B, W, A, Y and X were identified in two (8.7%), 15 (65.2%), two (8.7%), 1 (4.3%) and 1 (4.3%) cases, respectively (Figure 2). There were four deaths in this study period, all of them were caused by N. meningitidis serogroup B and three of them were under 1 year old. Conclusion. The epidemiology of meningococcal diseases has been varied in time with or without any apparent reasons. Hajj is a well-known cause for serogroup W epidemics and serogorup W was the most common cause of meningitis in Turkey during 2009–2014 as in other Middle East countries. After the impact of serogroup W epidemics related to Hajj seen in 2010’s was diminished, serogroup B has been leading cause of childhood meningitis since 2015. In countries affected from Hajj like Turkey, vaccination of children with serogroup B meningococcal vaccine as well as quadrivalentconjugated vaccine seems to be very important. It should be kept in mind that meningococcal epidemiology is dynamic and needed to be closely monitored to detect changes in years Disclosures All authors: No reported disclosures.

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Caesar, Nicole M., Kenneth A. Myers, and Xin Fan. "Neisseria meningitidis serogroup B vaccine development." Microbial Pathogenesis 57 (April 2013): 33–40. http://dx.doi.org/10.1016/j.micpath.2013.02.003.

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SUN, X., H. ZHOU, L. XU, H. YANG, Y. GAO, B. ZHU, and Z. SHAO. "Prevalence and genetic diversity of two adhesion-related genes, pilE and nadA, in Neisseria meningitidis in China." Epidemiology and Infection 141, no. 10 (January 7, 2013): 2163–72. http://dx.doi.org/10.1017/s0950268812002944.

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SUMMARYThe main Neisseria meningitidis adhesion molecules, type IV pili (Tfp) and Neisseria adhesion A (NadA), play important roles in the pathogenesis of invasive meningococcal disease. PilE is the major Tfp subunit. In this study, the prevalence and genetic diversity of pilE and nadA were investigated in the prevalent serogroups and clonal complexes (CC) of N. meningitidis isolated in China. All serogroup A strains belonging to CC1 and CC5 and all CC11 serogroup W135 strains were clustered into class II PilE clades. All serogroup C and most of serogroup B isolates except CC8 and ST5642 were class I PilE clades. Class II pilE sequences were highly conserved. All isolates belonging to class I PilE isolates were nadA negative. However, nadA-positive strains were exclusively found in CC5 and CC11 isolates (class II PilE). This study showed that PilE and NadA may be related to epidemic or endemic meningococcal disease.

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Moran, Elizabeth E., Robert Burden, Joseph E. Labrie, Zhiyun Wen, Xin-Min Wang, Wendell D. Zollinger, Lan Zhang, and Valerian B. Pinto. "Analysis of the Bactericidal Response to an Experimental Neisseria meningitidis Vesicle Vaccine." Clinical and Vaccine Immunology 19, no. 5 (March 29, 2012): 659–65. http://dx.doi.org/10.1128/cvi.00070-12.

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ABSTRACTRabbit immunogenicity studies on an experimental trivalent native outer membrane vesicle vaccine derived from three serogroup B strains were conducted to evaluate the effectiveness of this vaccine at inducing an antibody response with serum bactericidal activity against meningococcal strains of other serogroups in addition to serogroup B strains. The results showed that the vaccine was capable of inducing an effective broad-based bactericidal antibody response in rabbits against a small sample ofNeisseria meningitidisstrains of serogroups C, W135, and X and, to a lesser extent, serogroups A and Y. Analysis of antibody specificity using a bactericidal depletion assay revealed that antibodies to lipooligosaccharide (LOS), PorA, and NadA induced in rabbits by the experimental trivalent outer membrane vesicle vaccine were responsible for most of the bactericidal activity against strains of the otherN. meningitidisserogroups. In the case of serogroup AN. meningitidisstrains, the outer membrane antigen NadA was primarily responsible for protection. The outer membrane antigens fHbp and OpcA were also effective in removing some bactericidal activity from the sera.

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Diaz Romero, J., and I. M. Outschoorn. "Current status of meningococcal group B vaccine candidates: capsular or noncapsular?" Clinical Microbiology Reviews 7, no. 4 (October 1994): 559–75. http://dx.doi.org/10.1128/cmr.7.4.559.

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Meningococcal meningitis is a severe, life-threatening infection for which no adequate vaccine exists. Current vaccines, based on the group-specific capsular polysaccharides, provide short-term protection in adults against serogroups A and C but are ineffective in infants and do not induce protection against group B strains, the predominant cause of infection in western countries, because the purified serogroup B polysaccharide fails to elicit human bactericidal antibodies. Because of the poor immunogenicity of group B capsular polysaccharide, different noncapsular antigens have been considered for inclusion in a vaccine against this serogroup: outer membrane proteins, lipooligosaccharides, iron-regulated proteins, Lip, pili, CtrA, and the immunoglobulin A proteases. Alternatively, attempts to increase the immunogenicity of the capsular polysaccharide have been made by using noncovalent complexes with outer membrane proteins, chemical modifications, and structural analogs. Here, we review the strategies employed for the development of a vaccine for Neisseria meningitidis serogroup B; the difficulties associated with the different approaches are discussed.

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Ispasanie, Emma, Gerd Pluschke, Abraham Hodgson, Ali Sie, Calman MacLennan, and Oliver Koeberling. "Characterization of vaccine antigens of meningococcal serogroup W isolates from Ghana and Burkina Faso from 2003 to 2009." F1000Research 3 (November 3, 2014): 264. http://dx.doi.org/10.12688/f1000research.3881.1.

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Neisseria meningitidis is a major cause of bacterial meningitis and a considerable health problem in the 25 countries of the ‘African Meningitis Belt’ that extends from Senegal in West Africa to Ethiopia in the East. Approximately 80% of cases of meningococcal meningitis in Africa have been caused by strains belonging to capsular serogroup A. After the introduction of a serogroup A conjugate polysaccharide vaccine, MenAfriVac™, that began in December 2010, the incidence of meningitis due to serogroup A has markedly declined in this region. Currently, serogroup W of N. meningitidis accounts for the majority of cases. Vaccines based on sub-capsular antigens, such as Generalized Modules for Membrane Antigens (GMMA), are under investigation for use in Africa. To analyse the antigenic properties of a serogroup W wave of colonisation and disease, we investigated the molecular diversity of the protein vaccine antigens PorA, Neisserial Adhesin A (NadA), Neisserial heparin-binding antigen (NHBA) and factor H binding protein (fHbp) of 31 invasive and carriage serogroup W isolates collected as part of a longitudinal study from Ghana and Burkina Faso between 2003 and 2009. We found that the isolates all expressed fHbp variant 2 ID 22 or 23, differing from each other by only one amino acid, and a single PorA subtype of P1.5,2. Of the isolates, 49% had a functional nhbA gene and 100% had the nadA allele 3, which contained the insertion sequence IS1301 in five isolates. Of the W isolates tested, 41% had high fHbp expression when compared with a reference serogroup B strain, known to be a high expresser of fHbp variant 2. Our results indicate that in this collection of serogroup W isolates, there is limited antigenic diversification over time of vaccine candidate outer membrane proteins (OMP), thus making them promising candidates for inclusion in a protein-based vaccine against meningococcal meningitis for Africa.

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Kolb-Mäurer, Annette, Alexandra Unkmeir, Ulrike Kämmerer, Claudia Hübner, Thomas Leimbach, Anne Stade, Eckhart Kämpgen, Matthias Frosch, and Guido Dietrich. "Interaction of Neisseria meningitidis with Human Dendritic Cells." Infection and Immunity 69, no. 11 (November 1, 2001): 6912–22. http://dx.doi.org/10.1128/iai.69.11.6912-6922.2001.

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ABSTRACT Infection with Neisseria meningitidis serogroup B is responsible for fatal septicemia and meningococcal meningitis. The severity of disease directly correlates with the production of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-8. However, the source of these cytokines has not been clearly defined yet. Since bacterial infection involves the activation of dendritic cells (DCs), we analyzed the interaction of N. meningitidis with monocyte-derived DCs. Using N. meningitidis serogroup B wild-type and unencapsulated bacteria, we found that capsule expression significantly impaired neisserial adherence to DCs. In addition, phagocytic killing of the bacteria in the phagosome is reduced by at least 10- to 100-fold. However, all strains induced strong secretion of proinflammatory cytokines TNF-α, IL-6, and IL-8 by DCs (at least 1,000-fold at 20 h postinfection [p.i.]), with significantly increased cytokine levels being measurable by as early as 6 h p.i. Levels of IL-1β, in contrast, were increased only 200- to 400-fold at 20 h p.i. with barely measurable induction at 6 h p.i. Moreover, comparable amounts of cytokines were induced by bacterium-free supernatants of Neisseria cultures containing neisserial lipooligosaccharide as the main factor. Our data suggest that activated DCs may be a significant source of high levels of proinflammatory cytokines in neisserial infection and thereby may contribute to the pathology of meningococcal disease.

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TROTTER, C. L., N. J. GAY, and W. J. EDMUNDS. "The natural history of meningococcal carriage and disease." Epidemiology and Infection 134, no. 3 (October 20, 2005): 556–66. http://dx.doi.org/10.1017/s0950268805005339.

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The prevalence of Neisseria meningitidis carriage is highest in teenagers and lowest in young children. In contrast, invasive meningococcal disease is most common in young children with a smaller secondary peak in teenagers. Data on carriage and disease were analysed to quantify the risks of infection and disease by age and serogroup. The forces of infection for serogroups B, C, other meningococci and Neisseria lactamica were modelled together with the risk of disease given infection for serogroups B and C, using maximum likelihood to fit the models to the available data. The risk of meningococcal disease given infection declines steeply through childhood and is higher for serogroup C than for serogroup B. The secondary peak in disease in teenagers appears to be explained mostly by increased transmission although there is a suggestion that other factors may also contribute. These analyses provide important insights and may be used to guide further data collection and modelling studies.

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Swartley, John S., Li-Jun Liu, Yoon K. Miller, Larry E. Martin, Srilatha Edupuganti та David S. Stephens. "Characterization of the Gene Cassette Required for Biosynthesis of the (α1→6)-LinkedN-Acetyl-d-Mannosamine-1-Phosphate Capsule of Serogroup A Neisseria meningitidis". Journal of Bacteriology 180, № 6 (15 березня 1998): 1533–39. http://dx.doi.org/10.1128/jb.180.6.1533-1539.1998.

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ABSTRACT The (α1→6)-linkedN-acetyl-d-mannosamine-1-phosphate meningococcal capsule of serogroup A Neisseria meningitidisis biochemically distinct from the sialic acid-containing capsules produced by other disease-associated meningococcal serogroups (e.g., B, C, Y, and W-135). We defined the genetic cassette responsible for expression of the serogroup A capsule. The cassette comprised a 4,701-bp nucleotide sequence located between the outer membrane capsule transporter gene, ctrA, and galE, encoding the UDP-glucose-4-epimerase. Four open reading frames (ORFs) not found in the genomes of the other meningococcal serogroups were identified. The first serogroup A ORF was separated from ctrA by a 218-bp intergenic region. Reverse transcriptase (RT) PCR and primer extension studies of serogroup A mRNA showed that all four ORFs were cotranscribed in the opposite orientation to ctrA and that transcription of the ORFs was initiated from the intergenic region by a ς-70-type promoter that overlapped the ctrA promoter. The first ORF exhibited 58% amino acid identity with the UDP-N-acetyl-d-glucosamine (UDP-GlcNAc) 2-epimerase of Escherichia coli, which is responsible for the conversion of UDP-GlcNAc into UDP-N-acetyl-d-mannosamine. Polar or nonpolar mutagenesis of each of the ORFs resulted in an abrogation of serogroup A capsule production as determined by colony immunoblots and enzyme-linked immunosorbent assay. Replacement of the serogroup A biosynthetic gene cassette with a serogroup B cassette by transformation resulted in capsule switching from a serogroup A capsule to a serogroup B capsule. These data indicate that assembly of the serogroup A capsule likely begins with monomeric UDP-GlcNAc and requires proteins encoded by three other genes found in the serogroup A N. meningitidis-specific operon located betweenctrA and galE.

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Sacchi, Claudio Tavares, Ana Paula Silva de Lemos, Maria Cecília Outeiro Gorla, and Carl E. Frasch. "Monoclonal antibody to serotype 17 of Neisseria meningitidis and their prevalence in Brazilian States." Revista do Instituto de Medicina Tropical de São Paulo 37, no. 1 (February 1995): 1–5. http://dx.doi.org/10.1590/s0036-46651995000100001.

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Neisseria meningitidis are gram-negative diplococci responsible for cases of meningococcal disease all over the world. The epidemic potential of N. meningitidis serogroup B and C is clearly a function of their serotype antigens more than of their capsular polysaccharides. Until recently, hiperimmune sera were used to detect typing antigens on the bacteria. The advent of monoclonal antibodies (MAbs) offered the opportunity to eliminate many of the cross-reactions and have improved the accuracy and reproducibility of meningococcal serotyping. We have produced a MAb to the outer membrane protein of the already existent serotype 17 that have been detected by the use of hiperimmune rabbit sera. The prevalence of this serotype epitope is low in the Brazilian strains. By using the MAb 17 we could not decrease the percentage of nontypeable serogroup C strains. However, there were a decreasing in nontypeable strains to 13% into serogroup B strains and to 25% into the other serogroups.

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Mado, SM, U. Abubakar, SO Onazi, and GO Adeoye. "Epidemic cerebrospinal meningitis in children at Federal Medical Centre, Gusau, Zamfara state, Nigeria." Nigerian Journal of Paediatrics 40, no. 2 (April 8, 2013): 169–71. http://dx.doi.org/10.4314/njp.v40i2.12.

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Epidemic meningococcal meningitis is a major public health problem still affecting tropical countries, particularly in Sub-Saharan Africa, which lieswithin African meningitis belt. Repeated large scale epidemics of CSM have been reported in northern Nigeria for the past four decades. It is one of the important causes of morbidity and mortality in these regions. Mortality from the CSM remains high despite advances in treatment modalities. Neisseria meningitidis serogroup A have been the major cause of large scale epidemics in tropical countries, while serogroups B, C, Y and W-135 are responsible for most of invasive disease in America and other developed countries.Objective: To determine the pattern of epidemic CSM in children atFederal Medical Centre, Gusau.Method: The study was a retrospective one carried out in children agedsix months to 12 years admitted into Emergency Paediatrics Unit (EPU) with a diagnosis of CSM within the period January to May, 2009.Results: Seventy- seven children with epidemic CSM were admittedand managed in EPU from January-May 2009.Conclusion: Neisseria meningitidis serogroup A CSM is becoming thedisease of young infants, and stresses the need for inclusion ofCSM vaccine in early infancy in routine immunization policy, in areas within the meningitis belt in Sub-Saharan Africa.

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Soler-Garcia, Aleix, Mariona Fernández de Sevilla, Raquel Abad, Cristina Esteva, Laia Alsina, Julio Vázquez, Carmen Muñoz-Almagro, and Antoni Noguera-Julian. "Meningococcal Serogroup B Disease in Vaccinated Children." Journal of the Pediatric Infectious Diseases Society 9, no. 4 (October 21, 2019): 454–59. http://dx.doi.org/10.1093/jpids/piz071.

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Abstract Background Neisseria meningitidis serogroup B (MenB) is the most frequent cause of invasive meningococcal disease (IMD) in Spain. The multicomponent vaccine against MenB (4CMenB) was approved in Spain in January 2014. Methods We present 4 cases of children who developed MenB-associated IMD despite previous vaccination with 4CMenB. Extensive immunologic diagnostic work-up was performed in order to rule out any immunodeficiency. Also, molecular characterization of the MenB strain was conducted to determine whether bacterial antigens matched vaccine antigens. Results Among the 4 patients (2 girls), 2 had previous risk factors for IMD (recurrent bacterial meningitis of unknown origin and treatment with eculizumab). All patients developed meningitis, but only 2 developed septic shock; they were all cured without sequelae. No other primary or secondary immunodeficiencies were detected. MenB sequence type 213 was identified in 3 cases. With the exception of neisserial heparin-binding antigen peptide 465 present in 1 isolate, the rest of the isolated strains harbored vaccine antigen variants that did not match antigen variants included in the vaccine. Conclusions We present 4 children who developed MenB-associated IMD despite previous vaccination with 4CMenB. In 2 cases, the antibodies induced by 4CMenB likely were not effective against the isolated strains. A high level of suspicion for IMD seems advisable regardless of the patient’s vaccination history.

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de Filippis, Ivano. "Quest for a broad-range vaccine against Neisseria meningitidis serogroup B: implications of genetic variations of the surface-exposed proteins." Journal of Medical Microbiology 58, no. 9 (September 1, 2009): 1127–32. http://dx.doi.org/10.1099/jmm.0.011189-0.

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Despite the development of new vaccine formulations using new biotechnology resources to combat emerging and re-emerging diseases, serogroup B meningococcal disease is still a worldwide burden, accounting for many deaths and disabilities every year. The successful approach of coupling a polysaccharide (PS) with a carrier protein in order to increase long-lasting immunity could not be exploited against Neisseria meningitidis B because of the limitations of using the capsular PS of serogroup B meningococci. Tailor-made vaccines based on exposed proteins were shown to be a promising approach to overcome these flaws. However, the continuous adaptation of surface meningococcal structures to the external environment has led to genetic shifts of potential vaccine-target epitopes, hampering the quest for a broad-range vaccine that could be used against all serogroups, especially against serogroup B.

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Coppens, Isabelle, Sylvie Alonso, Rudy Antoine, Françoise Jacob-Dubuisson, Geneviève Renauld-Mongénie, Eric Jacobs, and Camille Locht. "Production of Neisseria meningitidisTransferrin-Binding Protein B by RecombinantBordetella pertussis." Infection and Immunity 69, no. 9 (September 1, 2001): 5440–46. http://dx.doi.org/10.1128/iai.69.9.5440-5446.2001.

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ABSTRACT Neisseria meningitidis serogroup B infections are among the major causes of fulminant septicemia and meningitis, especially severe in young children, and no broad vaccine is available yet. Because of poor immunogenicity of the serogroup B capsule, many efforts are now devoted to the identification of protective protein antigens. Among those are PorA and, more recently, transferrin-binding protein B (TbpB). In this study, TbpB of N. meningitidiswas genetically fused to the N-terminal domain of the Bordetella pertussis filamentous hemagglutinin (FHA), and thefha-tbpB hybrid gene was expressed in B. pertussis either as a plasmid-borne gene or as a single copy inserted into the chromosome. The hybrid protein was efficiently secreted by the recombinant strains, despite its large size, and was recognized by both anti-FHA and anti-TbpB antibodies. A single intranasal administration of recombinant virulent or pertussis-toxin-deficient, attenuated B. pertussis to mice resulted in the production of antigen-specific systemic immunoglobulin G (IgG), as well as local IgG and IgA. The anti-TbpB serum antibodies were of the IgG1, IgG2a, and IgG2b isotypes and were found to express complement-mediated bactericidal activity againstN. meningitidis. These observations indicate that recombinant B. pertussis may be a promising vector for the development of a mucosal vaccine against serogroup B meningococci.

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Honskus, Michal, Zuzana Okonji, Martin Musilek, and Pavla Krizova. "Whole genome sequencing of Neisseria meningitidis Y isolates collected in the Czech Republic in 1993-2018." PLOS ONE 17, no. 3 (March 10, 2022): e0265066. http://dx.doi.org/10.1371/journal.pone.0265066.

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Introduction The study presents the analysis of whole genome sequencing (WGS) data for Neisseria meningitidis serogroup Y isolates collected in the Czech Republic and their comparison to other countries. The aim of the study was to determine whether there are lineages of N. meningitidis serogroup Y in the Czech Republic genetically related to foreign ones that have been causing an increase of the morbidity and the mortality of invasive meningococcal disease (IMD) world-wide recently. Material and methods The WGS data of 43 Czech N. meningitidis Y isolates, 35 from IMD and 8 from healthy carriers were analysed. Due to the potential of meningococcal B vaccines to induce protection against non-B serogroups, the coverage of Czech isolates of N. meningitidis Y by these vaccines was studied. The WGS data of Czech, European and non-European isolates of N. meningitidis serogroup Y were compared. Results WGS assigned 36 isolates of N. meningitidis Y to five clonal complexes: cc23, cc92, cc167, cc103, and cc174, while seven isolates remained unassigned to any clonal complexes (ccUA). Eighteen invasive isolates belonged to clonal complex cc23, which was detected throughout the studied years. The occurrence of cc23 was recorded in all age groups of IMD patients, with the highest found in those aged 15–19 years. On the phylogenetic network isolates of cc23 form a separate lineage, distinct from all other isolates of N. meningitidis Y. The remaining isolates were assigned to other clonal complexes and have very low relatedness to cc23 isolates and to each other. The comparison with foreign WGS data showed that within the main genetic lineages, which are defined by clonal complexes, Czech isolates of N. meningitidis Y, similar to European ones, mostly cluster together and form geographical sublineages. Conclusions WGS analysis showed the population of Czech N. meningitidis Y isolates as relatively heterogeneous, containing a large number of genetic lineages. The Czech isolates of N. meningitidis Y follow the trend observed for European isolates. Our result was one of the bases for updating the recommended vaccination strategy in the Czech Republic.

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Unkmeir, Alexandra, Ulrike Kämmerer, Anne Stade, Claudia Hübner, Sabine Haller, Annette Kolb-Mäurer, Matthias Frosch, and Guido Dietrich. "Lipooligosaccharide and Polysaccharide Capsule: Virulence Factors of Neisseria meningitidis That Determine Meningococcal Interaction with Human Dendritic Cells." Infection and Immunity 70, no. 5 (May 2002): 2454–62. http://dx.doi.org/10.1128/iai.70.5.2454-2462.2002.

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ABSTRACT In this work we analyzed the roles of meningococcal lipooligosaccharide (LOS) and capsule expression in the interaction of Neisseria meningitidis with human dendritic cells (DC). Infection of DC with serogroup B wild-type meningococci induced a strong burst of the proinflammatory cytokines and chemokines tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8. In contrast, a serogroup B mutant strain lacking LOS expression barely led to cytokine induction, demonstrating that meningococcal LOS is the main mediator of the proinflammatory response in human DC. Sialylation of meningococcal LOS did not influence cytokine secretion by DC. However, we found the phagocytosis of N. meningitidis by human DC to be inhibited by LOS sialylation. In addition, the expression of the meningococcal serogroup A, B, and C capsules dramatically reduced DC adherence of N. meningitidis and phagocytosis to some extent. Hence, LOS sialylation and capsule expression are independent mechanisms protecting N. meningitidis from the phagocytic activity of human DC.

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KYAW, M. H., J. C. BRAMLEY, S. CLARKE, P. CHRISTIE, I. G. JONES, and H. CAMPBELL. "Prevalence of moderate penicillin resistant invasive Neisseria meningitidis infection in Scotland, 1994–9." Epidemiology and Infection 128, no. 2 (December 2001): 149–56. http://dx.doi.org/10.1017/s0950268801006549.

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We examined the serological characteristics of 774 invasive meningococcal isolates collected through an active laboratory-based surveillance system in Scotland from 1994 to 1999. Of these, 72–73% of isolates were tested for susceptibility to several antimicrobial agents. Meningococci with high-level resistance to sulphadiazine had a prevalence of 10% and incidence of 0·22 per 100000 population. High-level resistance to penicillin and other antibiotics was not detected. The prevalence of moderate penicillin resistant meningococci was 8·3%. There was no increase in moderate penicillin resistant meningococcal isolates during the study period, but there were temporal and geographic variations. The estimated incidence of moderate penicillin resistant meningococci was 0·15 per 100000 population. High and low incidence of moderate penicillin resistant meningococci appeared to correlate with the number of doses of penicillin prescribed in some geographic locations. The majority of moderate penicillin resistant isolates belonged to serogroups B (52·2%) and C (39·2%). However, the prevalence of moderate penicillin resistance in serogroup W135 was substantially higher (51·7%) than serogroups B (7·8%) and C (7·6%). Serogroup W135 accounted for a higher proportion of moderate penicillin resistance (8·7%) than disease (1%). There was no predominant penicillin resistant serotype/subtype within any serogroup. Constant surveillance is necessary to monitor the emergence and spread of resistance and to guide appropriate public health interventions in preventing drug resistant meningococci.

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Sharp, Susan E., and Robert J. Poppiti. "Neisseria meningitidis serogroup B meningitis with a negative direct antigen test." Clinical Microbiology Newsletter 12, no. 23 (December 1990): 183. http://dx.doi.org/10.1016/0196-4399(90)90040-i.

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Tondella, Maria Lucia C., Mike W. Reeves, Tanja Popovic, Nancy Rosenstein, Brian P. Holloway, and Leonard W. Mayer. "Cleavase Fragment Length Polymorphism Analysis of Neisseria meningitidis Basic Metabolic Genes." Journal of Clinical Microbiology 37, no. 8 (1999): 2402–7. http://dx.doi.org/10.1128/jcm.37.8.2402-2407.1999.

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Cleavase fragment length polymorphism (CFLP) is a subtyping system based on the property of the enzyme cleavase to recognize junctions between single- and double-stranded regions of DNA formed after denaturation and cooling. To assess the capacity of CFLP for discriminating Neisseria meningitidis serogroup B strains belonging to the electrophoretic type (ET) 5 (ET-5) complex from other serogroup B strains, 30 serogroup B N. meningitidisisolates were subtyped by CFLP with internal fragments of five housekeeping genes, adk, aspC,carA, dhp, and glnA. Two genes (glnA and carA) which demonstrated a high degree of diversity for the serogroup B isolates were then used to further evaluate the suitability of CFLP for screening 50 serogroup CN. meningitidis outbreak-associated and sporadic-case isolates with a single metabolic gene. The results were compared to those from multilocus enzyme electrophoresis (MEE), the current standard subtyping method. CFLP was able to distinguish the ET-5 complex isolates from other serogroup B isolates as efficiently as MEE. Furthermore, CFLP analysis of a single gene was sufficient to identify and cluster the serogroup C isolates belonging to the ET-37 complex from other, unrelated serogroup C isolates but was not capable of differentiating between the isolates of the major individual ETs of this complex (ET-17 and ET-24) causing most serogroup C meningococcal disease outbreaks in the United States. CFLP based on a single gene with a high degree of diversity but not under selective pressure can be applied to the rapid screening of a large number of isolates related to the recognized epidemic complex ET-5 or ET-37. Additionally, CFLP can be used as an initial screening tool to survey the amount of diversity in genes that might be used to develop a DNA sequence-based subtyping system.

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Moe, G. R., P. Zuno-Mitchell, S. S. Lee, A. H. Lucas, and D. M. Granoff. "Functional Activity of Anti-Neisserial Surface Protein A Monoclonal Antibodies against Strains of Neisseria meningitidis Serogroup B." Infection and Immunity 69, no. 6 (June 1, 2001): 3762–71. http://dx.doi.org/10.1128/iai.69.6.3762-3771.2001.

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ABSTRACT Neisserial surface protein A (NspA) is currently being investigated with humans as a candidate vaccine for the prevention of meningococcal disease. Although NspA is highly conserved, the ability of anti-NspA antibodies to bind to or elicit complement-mediated bactericidal activity against diverse Neisseria meningitidis serogroup B strains is controversial. To evaluate strain differences in NspA surface accessibility and susceptibility to bactericidal activity, we prepared murine immunoglobulin G2a anti-NspA monoclonal antibodies (MAbs) and evaluated their functional activity against 10 genetically diverse N. meningitidis serogroup B strains. By colony Western blot, all 10 strains expressed NspA as detected by one or more MAbs. By flow cytometry, two MAbs were found to bind to the bacterial surface of 6 of the 10 strains. In addition, two strains showed variable NspA surface accessibility for the MAbs despite being uniformly positive for NspA expression by colony Western blotting. Only 4 of the 10 strains were susceptible to anti-NspA complement-mediated bacteriolysis. Passively administered MAb protected infant rats from developing bacteremia after challenge with N. meningitidisserogroup B strain 8047 (surface binding positive, susceptible to anti-NspA bacteriolysis), was poorly protective against strain BZ232 (surface binding variable, resistant to bacteriolysis), and did not protect against strain M986 (surface binding negative, resistant to bacteriolysis). Finally, NspA does not appear to be critical for causing bacteremia, as an NspA knockout from strain 8047 was highly virulent in infant rats. Taken together, these findings suggest that an NspA-based vaccine will need to incorporate additional antigens to elicit broad protection against N. meningitidis serogroup B.

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Kostyukova, N. N., and V. A. Bekhalo. "Current Meningococcal Vaccines: Advantages and Disadvantages and New Challenges." Epidemiology and Vaccine Prevention 15, no. 4 (August 20, 2016): 64–73. http://dx.doi.org/10.31631/2073-3046-2016-15-4-64-73.

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The article reviews and analyses the vaccines against invasive meningococcal disease, widely used in practice since 70s-80s of the last century, as well as newly developed ones, the efficacy of which is not completely clear yet. The advantages and disadvantages of polysaccharide and glycoprotein vaccines against meningococci of serogroups A, C, Y, W135 and of protein «vesicle» and geneticengineering vaccines based on «reverse vaccinology» against serogroup B are discussed. Some options for composition of future vaccines under development are presented. Briefly the meningococcal vaccines used in Russia are described. Among the most important immediate tasks discussed are: the study of the duration and intensity of protection after immunization with conjugate vaccines; the development and subsequent trials of a vaccine against serogroup X; further study and improvement of vaccines against serogroup B, as well as the creation of a single vaccine product that protects against all antigenic variants of Neisseria meningitidis.

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LEMOS, Ana Paula S., Claudio T. SACCHI, Maria V. PAIVA, Teresa I. YARA, Carmo Elias A. MELLES, and Leonard W. MAYER. "Genetic relationships among serogroup B: serotype 4 Neisseria meningitidis strains." Revista do Instituto de Medicina Tropical de São Paulo 43, no. 3 (June 2001): 119–24. http://dx.doi.org/10.1590/s0036-46652001000300001.

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We compared the results obtained by serotyping of PorB epitopes using an expanded panel of monoclonal antibodies (mAb) including mAb 7 and mAb 10, with results obtained by RFLP of rRNA genes (ribotyping). The purpose of this study was to assess the correlation between phenotypic- and genotypic- methods for typing N. meningitidis. The ribotypes obtained using ClaI or EcoRV endonucleases grouped the strains in seven and two different patterns, respectively. This additional characterization of PorB epitopes improved the correlation between these two methods of typing N. meningitidis.

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Bettinger, Julie, Manish Sadarangani, Nicole Le Saux, Shaun Morris, Karina Top, Scott Halperin, and Raymond Tsang. "57 Update of IMPACT Invasive Meningococcal Surveillance, 2016-2020." Paediatrics & Child Health 27, Supplement_3 (October 1, 2022): e27-e28. http://dx.doi.org/10.1093/pch/pxac100.056.

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Abstract Background Meningococcal conjugate vaccine (MCV) programs in Canada began in 2002. Objectives This study examines the most recent surveillance data to describe the current Canadian epidemiology of invasive meningococcal disease (IMD) and the effect of MCV programs, especially on age and serogroup distribution. Design/Methods Active metropolitan area surveillance for hospitalization of adults and children due to IMD, which was defined as a clinical infection with Neisseria meningitidis isolated or detected by molecular methods or culture from a sterile body site. The study was conducted via the 12 centres of the Canadian Immunization Monitoring Program, Active (IMPACT) network from January 1, 2016 – December 31, 2020. Results During 2016-2020, a total of 105 pediatric (<20 years of age) and 145 adult IMD cases occurred. Serogroup B accounted for the greatest proportion of pediatric cases (N=58, 55.2%), followed by W (n=19, 18.1%) and Y (n=9, 8.6%) and C (n=2, 1.9%). Among adults, serogroup W accounted for the majority of cases (n=55, 38.0%), followed by Y (n=41, 28.3%), B (n=33, 22.8%) and C (n=7, 4.8%). The age distribution for serogroups covered by MCV programs has shifted to adults. The median age was 24.2 years (33.4 mean). Whereas the median age of serogroup B cases was 7.7 years (19.4 years mean) with 63.7% of cases occurring in children < 19 years of age and 46.2% in children 0-4 years of age. A total of 20 people died from meningococcal infections in 2016–2020. Five deaths were in children, four from serogroup B and one from serogroup W. Fifteen deaths were in adults, one from serogroup B, eight from serogroup W, three from serogroup Y, and three from Non-typeable/Other/Unknown serogroups. Conclusion Serogroup B, which is not covered by MCV programs, still accounts for the majority of pediatric IMD. Serogroup C has been controlled and rarely causes pediatric infection. With the implementation of MCV programs in children and adolescents, the median and mean age at infection has increased across all serogroups, except serogroup B. Serogroup W is still causing IMD among pediatric age groups.

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Johswich, Kay O., Jianwei Zhou, Dennis K. S. Law, Frank St. Michael, Shannon E. McCaw, Frances B. Jamieson, Andrew D. Cox, Raymond S. W. Tsang, and Scott D. Gray-Owen. "Invasive Potential of Nonencapsulated Disease Isolates of Neisseria meningitidis." Infection and Immunity 80, no. 7 (April 16, 2012): 2346–53. http://dx.doi.org/10.1128/iai.00293-12.

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ABSTRACTThe capsule ofNeisseria meningitidisis the major virulence factor that enables this bacterium to overcome host immunity elicited by complement and phagocytes, rendering it capable of surviving in blood. As such, nonencapsulatedN. meningitidisisolates are generally considered nonpathogenic. Here, we consider the inherent virulence of two nonencapsulatedN. meningitidisisolates obtained from our national surveillance of infected blood cultures in Canada. Capsule deficiency of both strains was confirmed by serology and PCR for thectrAtoctrDgenes andsiaAtosiaCgenes, as well assiaDgenes specific to serogroups B, C, Y, and W135. In both strains, the capsule synthesis genes were replaced by the capsule null locus,cnl-2. In accordance with a lack of capsule, both strains were fully susceptible to killing by both human and baby rabbit complement. However, in the presence of cytidine-5′ monophospho-N-acetylneuraminic acid (CMP-NANA), allowing for lipooligosaccharide (LOS) sialylation, a significant increase of resistance to complement killing was observed. Mass spectrometry of purified LOS did not reveal any uncommon modifications that would explain their invasive phenotype. Finally, in a mouse intraperitoneal challenge model, these nonencapsulated isolates displayed enhanced virulence relative to an isogenic mutant of serogroup B strain MC58 lacking capsule (MC58ΔsiaD). Virulence of all nonencapsulated isolates tested was below that of encapsulated serogroup B strains MC58 and B16B6. However, whereas no mortality was observed with MC58ΔsiaD, 5/10 mice succumbed to infection with strain 2275 and 2/11 mice succumbed to strain 2274. Our results suggest the acquisition of a new virulence phenotype by these nonencapsulated strains.

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Haghi, Fakhri, Shahin Najar Peerayeh, Seyed Davar Siadat, and Mehran Montajabiniat. "Cloning, expression and purification of outer membrane protein PorA of Neisseria meningitidis serogroup B." Journal of Infection in Developing Countries 5, no. 12 (November 14, 2011): 856–62. http://dx.doi.org/10.3855/jidc.1557.

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Introduction: Neisseria meningitidis is a major causative agent of bacterial septicemia and meningitis in humans. Currently, there are no vaccines to prevent disease caused by strains of N. meningitidis serogroup B. PorA is a major component of the outer membrane of N. meningitidis and functions as a cationic porin. This study aimed to clone and determine the expression of PorA. Methodology: A 1200 bp fragment of porA gene was amplified by PCR from serogroup B N. meningitidis and then cloned into prokaryotic expression vector pET-32a. For expression of recombinant protein, pET32a-porA plasmid was transformed into competent Origami B (DE3) cells. Recombinant protein was overexpressed with isopropythio-beta-D-galctoside (IPTG) and affinity purified by Ni-NTA agarose. SDS-PAGE and western blotting were performed for protein determination and verification. Results: Cloning of porA was confirmed by colony-PCR and enzymatic digestion. In comparison with the corresponding sequences of original genes, the nucleotide sequence homology of the cloned porA gene was 97%. IPTG with a dosage of 1.0 mmol/L could efficiently induce protein expression. SDS-PAGE analysis showed that our constructed prokaryotic expression system pET32a-PorA-Origami efficiently produces a target recombinant protein with a molecular weight of 65 kDa. The recombinant PorA was overexpressed as inclusion bodies and reacted with the serum from a rabbit previously immunized with native outer membrane vesicle. Conclusion: This prokaryotic expression system provides an easy method for producing recombinant PorA and may also be useful for the production of other bacterial outer membrane proteins for vaccine studies.

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de Filippis, Ivano, Ana Paula S. de Lemos, Jessica B. Hostetler, Kurt Wollenberg, Claudio T. Sacchi, Lee H. Harrison, Margaret C. Bash, and D. Rebecca Prevots. "Molecular Epidemiology of Neisseria meningitidis Serogroup B in Brazil." PLoS ONE 7, no. 3 (March 14, 2012): e33016. http://dx.doi.org/10.1371/journal.pone.0033016.

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Böhm, Raphael, Friedrich Freiberger, Katharina Stummeyer, Rita Gerardy-Schahn, Mark von Itzstein, and Thomas Haselhorst. "Neisseria meningitidis Serogroup B Polysialyltransferase: Insights into Substrate Binding." ChemBioChem 11, no. 2 (January 25, 2010): 170–74. http://dx.doi.org/10.1002/cbic.200900659.

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Balmer, Paul, and Laura J. York. "Optimal use of meningococcal serogroup B vaccines: moving beyond outbreak control." Therapeutic Advances in Vaccines and Immunotherapy 6, no. 3 (June 2018): 49–60. http://dx.doi.org/10.1177/2515135518781757.

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Neisseria meningitidis is a major cause of meningitis and septicemia globally. Vaccines directed against N. meningitidis serogroup B (MenB) have been used to control sporadic and sustained disease in industrialized and non-industrialized countries. Early outer membrane vesicle (OMV) vaccines effectively reduced MenB disease in countries such as Norway, New Zealand, and France; however, these vaccines were highly specific for their targeted outbreak strain, did not elicit a durable immune response, and were ineffective for widespread use due to the diversity of MenB-disease-causing isolates. Recently developed recombinant protein-based MenB vaccines that target conserved surface proteins have the potential to induce a broader immune response against the diversity of disease-causing strains. Given the deleterious consequences and sporadic nature of MenB disease, the use of optimal vaccination strategies is crucial for prevention. Reactive vaccination strategies used in the past have significant limitations, including delayed implementation, substantial use of resources, and time constraints. The broad coverage potential of recombinant protein-based MenB vaccines suggests that routine use could result in a reduced burden of disease. Despite this, routine use of MenB vaccines is currently limited in practice.

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Langereis, Jeroen D., Bryan van den Broek, Sjoerd Franssen, Irma Joosten, Nicole M. A. Blijlevens, Marien I. de Jonge, and Saskia Langemeijer. "Eculizumab impairs Neisseria meningitidis serogroup B killing in whole blood despite 4CMenB vaccination of PNH patients." Blood Advances 4, no. 15 (August 7, 2020): 3615–20. http://dx.doi.org/10.1182/bloodadvances.2020002497.

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Abstract Complement C5 inhibitor eculizumab has a great impact on the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). However, this treatment success has a major drawback: a substantially increased susceptibility for life-threatening Neisseria meningitidis infections. Therefore, N meningitidis vaccination is strongly advised before initiating complement C5–blocking therapy. In this study, we show that the multicomponent N meningitidis serogroup B (4CMenB) vaccination of PNH patients treated with eculizumab results in a significant increase in anti–N meningitidis serogroup B (MenB) plasma immunoglobulin G (IgG) levels. Anti-MenB IgG was able to bind to the bacterial surface and initiate complement activation; however, inhibition of the membrane attack complex formation completely blocked whole blood–mediated killing of MenB. This would suggest that, despite 4CMenB vaccination, PNH patients taking C5 inhibitors are not sufficiently protected against MenB infection, which is in line with the fact that vaccinated PNH patients still experience meningococcal infections.

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Semchenko, Evgeny A., Aimee Tan, Ray Borrow, and Kate L. Seib. "The Serogroup B Meningococcal Vaccine Bexsero Elicits Antibodies to Neisseria gonorrhoeae." Clinical Infectious Diseases 69, no. 7 (December 14, 2018): 1101–11. http://dx.doi.org/10.1093/cid/ciy1061.

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Abstract Background Neisseria gonorrhoeae and Neisseria meningitidis are closely-related bacteria that cause a significant global burden of disease. Control of gonorrhoea is becoming increasingly difficult, due to widespread antibiotic resistance. While vaccines are routinely used for N. meningitidis, no vaccine is available for N. gonorrhoeae. Recently, the outer membrane vesicle (OMV) meningococcal B vaccine, MeNZB, was reported to be associated with reduced rates of gonorrhoea following a mass vaccination campaign in New Zealand. To probe the basis for this protection, we assessed the cross-reactivity to N. gonorrhoeae of serum raised to the meningococcal vaccine Bexsero, which contains the MeNZB OMV component plus 3 recombinant antigens (Neisseria adhesin A, factor H binding protein [fHbp]-GNA2091, and Neisserial heparin binding antigen [NHBA]-GNA1030). Methods A bioinformatic analysis was performed to assess the similarity of MeNZB OMV and Bexsero antigens to gonococcal proteins. Rabbits were immunized with the OMV component or the 3 recombinant antigens of Bexsero, and Western blots and enzyme-linked immunosorbent assays were used to assess the generation of antibodies recognizing N. gonorrhoeae. Serum from humans immunized with Bexsero was investigated to assess the nature of the anti-gonococcal response. Results There is a high level of sequence identity between MeNZB OMV and Bexsero OMV antigens, and between the antigens and gonococcal proteins. NHBA is the only Bexsero recombinant antigen that is conserved and surfaced exposed in N. gonorrhoeae. Bexsero induces antibodies in humans that recognize gonococcal proteins. Conclusions The anti-gonococcal antibodies induced by MeNZB-like OMV proteins could explain the previously-seen decrease in gonorrhoea following MeNZB vaccination. The high level of human anti-gonococcal NHBA antibodies generated by Bexsero vaccination may provide additional cross-protection against gonorrhoea.

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Sorhouet Pereira, Cecilia, Mabel Regueira, and Marta Mollerach. "PorA types in Neisseria meningitidis serogroup B isolated in Argentina from 2001 to 2003: implications for the design of an outer membrane protein-based vaccine." Journal of Medical Microbiology 57, no. 3 (March 1, 2008): 338–42. http://dx.doi.org/10.1099/jmm.0.47631-0.

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Identification of Neisseria meningitidis PorA types remains important, as the PorA protein is a major immunogenic component of several meningococcal vaccines under development. In this study, 191 N. meningitidis serogroup B isolates collected in Argentina through active laboratory-based surveillance from 2001 to 2003 were serosubtyped. Nucleotide sequences of the porA variable region 1 (VR1) and VR2 regions were determined in 52 non-serosubtypeable isolates. A substantial number of distinct VR types were identified, and a new VR2 variant from the P1.16 family was described. This is the first report describing PorA types in N. meningitidis serogroup B isolates in Argentina. Furthermore, the wide diversity of subtypes detected by serosubtyping and genosubtyping reveals the difficulty in designing a useful outer-membrane vaccine applicable in this country. A possible mechanism responsible for altered PorA expression was analysed in two PorA types.

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Seyed, Davar Siadat, Reza Naddaf Saied, Zangeneh Mehrangiz, Moshiri Arfa, Mehdi Sadat Seyed, Shafiee Ardestani Mehdi, Hassan Pouriayevali Mohammad, Amini Safieh, and Reza Aghasadeghi Mohammad. "Outer membrane vesicle of Neisseria meningitidis serogroup B as an adjuvant in immunization of rabbit against Neisseria meningitidis serogroup A." African Journal of Microbiology Research 5, no. 19 (September 23, 2011): 3090–95. http://dx.doi.org/10.5897/ajmr11.361.

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., S. D. Siadat, D. Norouzian ., B. Tabaraie ., H. Ahmadi ., Q. Behzadiyannejad ., S. N. Pirayeeh ., M. Nejati ., and B. A. Motlagh . "Comparative Studies of Conjugated Capsular Polysaccharide of Neisseria meningitidis Serogroup A with Outer Membrane Vesicle of Neisseria meningitidis Serogroup B." Research Journal of Microbiology 2, no. 4 (April 1, 2007): 337–45. http://dx.doi.org/10.3923/jm.2007.337.345.

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Pizza, Mariagrazia, Rafik Bekkat-Berkani, and Rino Rappuoli. "Vaccines against Meningococcal Diseases." Microorganisms 8, no. 10 (October 3, 2020): 1521. http://dx.doi.org/10.3390/microorganisms8101521.

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Neisseria meningitidis is the main cause of meningitis and sepsis, potentially life-threatening conditions. Thanks to advancements in vaccine development, vaccines are now available for five out of six meningococcal disease-causing serogroups (A, B, C, W, and Y). Vaccination programs with monovalent meningococcal serogroup C (MenC) conjugate vaccines in Europe have successfully decreased MenC disease and carriage. The use of a monovalent MenA conjugate vaccine in the African meningitis belt has led to a near elimination of MenA disease. Due to the emergence of non-vaccine serogroups, recommendations have gradually shifted, in many countries, from monovalent conjugate vaccines to quadrivalent MenACWY conjugate vaccines to provide broader protection. Recent real-world effectiveness of broad-coverage, protein-based MenB vaccines has been reassuring. Vaccines are also used to control meningococcal outbreaks. Despite major improvements, meningococcal disease remains a global public health concern. Further research into changing epidemiology is needed. Ongoing efforts are being made to develop next-generation, pentavalent vaccines including a MenACWYX conjugate vaccine and a MenACWY conjugate vaccine combined with MenB, which are expected to contribute to the global control of meningitis.

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Kostyukova, N. N., and V. A. Bekhalo. "Meningococcal Vaccines of New Generations – the First 20 Years of Use." Epidemiology and Vaccinal Prevention 20, no. 4 (September 4, 2021): 103–13. http://dx.doi.org/10.31631/2073-3046-2021-20-4-103-113.

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Relevance. Meningococcal vaccine refers to any of the vaccines used to prevent infection by Neisseria meningitidis. Therefore, there is a great scientific and practical interest in the existing and developed menicococcal vaccines.Aims the review is to provide an analysis: literature data on the effectiveness of meningococcal vaccines of new generations - conjugated polysaccharide serogroups A, C, W and Y and protein serogroup B.Conclusions. With regard to conjugated vaccines, there are a large number of reliable observations confirming the high immunological and epidemiological effectiveness of these vaccine preparations, including the prevention of bacterial carriage and the development of herd immunity. These vaccines are weakly reactogenic, and in many countries, they are introduced into national immunization programs and in some countries are used as mandatory (UK) or in connection with the existing epidemic indications. The protein «vesicle» vaccine based on serogroup B meningococcal outer membrane proteins, showed high efficacy only in those cases when the protein composition of the strain that caused the morbidity corresponded to the composition (mainly in terms of the PorA subtype antigen) of the vaccine. Genetic-engineered vaccines containing only a few serogroup B meningococcal protein antigens with or without the addition of «vesicle» proteins are difficult to evaluate due to the small number of observations associated with low serogroup В prevalence, but in Great Britain, such vaccine was also introduced as mandatory in the national immunization schedule for babies. At the same time, new vaccines of serogroup B induce immune protection against some strains of meningococcus of other serogroups C, W, and Y, and even against other species of Neisseria, in particular - gonococcus. This circumstance gives rise to hope for the development of protein meningococcal vaccines with a wider spectrum of specificity than the group, and even than the species.

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Mironov, Konstantin O., E. A. Yarygina, Aida Chagaryan, and Nataly Ivanchik. "The genetic characteristics of Neisseria meningitidis causing invasive meningococcal infections in Smolensk region." Clinical Microbiology and Antimicrobial Chemotherapy 22, no. 2 (2020): 92–95. http://dx.doi.org/10.36488/cmac.2020.2.92-95.

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Objective. To determine antigenic and genetic characteristics of Neisseria meningitidis isolated from the patients with invasive meningococcal infections in Smolensk region in comparison with those circulating in other regions. Materials and Methods. A total of 14 cerebrospinal fluid samples obtained in 2016–2019 and containing N. meningitidis DNA were tested using AmpliSens® Nm-ABCW kit, multilocus sequence typing and antigenic finetyping of outer membrane proteins. The results were analyzed by the BURST algorithm and other functionalities available at PubMLST.org (Jolley K. et al. 2018). Results. The variable region alleles, sequence types and clonal complexes were determined for the tested isolates. The genotyping results were published in the PubMLST database (https://pubmlst.org/neisseria/). Most of N. meningitidis serogroup B isolates (n = 6) belonged to sequence types which have not been described previously: ST-14705, ST-14710, ST-14711, ST-14713 and ST-14717. Sequence types of serogroup C isolates (n = 7) were usual for strains circulating in other Russian regions (4 of 7 belonged to ST-8416). The only serogroup Y isolate belonged to ST-11585. Conclusions. Most studied N. meningitidis sequence types belonged to clonal complexes designated in PubMLST database and groups of isolates, determined by the BURST algorithm, which were usual for Russian regions. The antigenic and genetic characteristics suggest no circulation of epidemiologically significant N. meningitidis strains or hypervirulent strains on the observed territory.

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O'Dwyer, Clíona A., Karen Reddin, Denis Martin, Stephen C. Taylor, Andrew R. Gorringe, Michael J. Hudson, Bernard R. Brodeur, Paul R. Langford, and J. Simon Kroll. "Expression of Heterologous Antigens in Commensal Neisseria spp.: Preservation of Conformational Epitopes with Vaccine Potential." Infection and Immunity 72, no. 11 (November 2004): 6511–18. http://dx.doi.org/10.1128/iai.72.11.6511-6518.2004.

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ABSTRACT Commensal neisseriae share with Neisseria meningitidis (meningococcus) a tendency towards overproduction of the bacterial outer envelope, leading to the formation and release during growth of outer membrane vesicles (OMVs). OMVs from both meningococci and commensal neisseriae have shown promise as vaccines to protect against meningococcal disease. We report here the successful expression at high levels of heterologous proteins in commensal neisseriae and the display, in its native conformation, of one meningococcal outer membrane protein vaccine candidate, NspA, in OMVs prepared from such a recombinant Neisseria flavescens strain. These NspA-containing OMVs conferred protection against otherwise lethal intraperitoneal challenge of mice with N. meningitidis serogroup B, and sera raised against them mediated opsonophagocytosis of meningococcal strains expressing this antigen. This development promises to facilitate the design of novel vaccines containing membrane protein antigens that are otherwise difficult to present in native conformation that provide cross-protective efficacy in the prevention of meningococcal disease.

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Rameix-Welti, Marie-Anne, Maria Leticia Zarantonelli, Dario Giorgini, Corinne Ruckly, Monica Marasescu, Sylvie van der Werf, Jean-Michel Alonso, Nadia Naffakh, and Muhamed-Kheir Taha. "Influenza A Virus Neuraminidase Enhances Meningococcal Adhesion to Epithelial Cells through Interaction with Sialic Acid-Containing Meningococcal Capsules." Infection and Immunity 77, no. 9 (June 15, 2009): 3588–95. http://dx.doi.org/10.1128/iai.00155-09.

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ABSTRACT The underlying mechanisms of the epidemiological association between influenza virus infections and Neisseria meningitidis invasive infections are not fully understood. Here we report that adhesion of N. meningitidis to human Hec-1-B epithelial cells is enhanced by influenza A virus (IAV) infection. A potential role of the viral neuraminidase (NA) in facilitating meningococcal adhesion to influenza virus-infected epithelial cells was examined. Expression of a recombinant IAV NA in Hec-1-B human epithelial cells increased the adhesion of strains of N. meningitidis belonging to the sialic acid-containing capsular serogroups B, C, and W135 but not to the mannosamine phosphate-containing capsular serogroup A. Adhesion enhancement was not observed with an inactive NA mutant or in the presence of an NA inhibitor (zanamivir). Furthermore, purified IAV NA was shown to cleave sialic acid-containing capsular polysaccharides of N. meningitidis. On the whole, our findings suggest that a direct interaction between the NA of IAV and the capsule of N. meningitidis enhances bacterial adhesion to cultured epithelial cells, most likely through cleavage of capsular sialic acid-containing polysaccharides. A better understanding of the association between IAV and invasive meningococcal infections should help to set up improved control strategies against these seasonal dual viral-bacterial infections.

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HSUEH, P. R., L. J. TENG, T. Y. LIN, K. T. CHEN, H. M. HSU, S. J. TWU, S. W. HO, and K. T. LUH. "Re-emergence of meningococcal disease in Taiwan: circulation of domestic clones of Neisseria meningitidis in the 2001 outbreak." Epidemiology and Infection 132, no. 4 (July 9, 2004): 637–45. http://dx.doi.org/10.1017/s0950268804002316.

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The annual incidence of meningococcal disease (meningitis and septicaemia) in Taiwan was 0·94/105 population in 1953. It then declined to below 0·001 from 1980 to 1987, and re-emerged in 2000 with a rate of 0·07/105 population. In 2001 there was a further increase in incidence (43 cases, 0·19/105). Of 43 isolates of Neisseria meningitidis available for this study, including 41 from patients treated in 2001, three (7·0%) were penicillin insensitive (MIC [ges ]0·12 μg/ml), though all were β-lactamase negative; 16 (37·2%) were resistant to trimethoprim–sulphamethoxazole sulphamethoxazole (MIC [ges ]4/76 μg/ml). Serogrouping and genotype analysis revealed nine domestic clones. None of the 43 patients had any relationship (travel or contact history) with the 2000 or 2001 Hajj pilgrimage. Epidemiological information and typing results suggested wide dissemination of a limited number of domestic clones of N. meningitidis, manifesting as serogroups W-135, B and Y. Two clones of serogroup W-135 involved in the outbreak were genetically distinct from the 2000 or 2001 Hajj-related W-135 clone.

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Richardson, Anthony R., and Igor Stojiljkovic. "HmbR, a Hemoglobin-Binding Outer Membrane Protein of Neisseria meningitidis, Undergoes Phase Variation." Journal of Bacteriology 181, no. 7 (April 1, 1999): 2067–74. http://dx.doi.org/10.1128/jb.181.7.2067-2074.1999.

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ABSTRACT Neisseria meningitidis uses hemoglobin (Hb) as an iron source via two TonB-dependent outer membrane receptors, HmbR and HpuB. Analysis of 25 epidemiologically unrelated clinical isolates from serogroups A, B, C, and Y revealed that 64% strains possessed both Hb receptor genes. Examination of the hmbR expression pattern in strains in which the hpuB gene was genetically inactivated revealed two distinct Hb utilization phenotypes. Five strains retained the ability to grow as a confluent lawn, while seven grew only as single colonies around Hb discs. The single-colony phenotype observed for some hpuB mutants is suggestive of phase variation of hmbR. The length of the poly(G) tract starting at position +1164 of hmbR absolutely correlated with the two Hb utilization phenotypes. All five strains that grew as confluent lawns around Hb discs possessed either 9 or 12 consecutive G residues. All seven strains that grew as single colonies around Hb discs had poly(G) tracts of a length other than 9 or 12. These single-colony variants that arose around the Hb discs had poly(G) tracts with either 9 or 12 consecutive G residues restoring thehmbR reading frame. Inactivation of hmbR in these strains resulted in a loss of Hb utilization, demonstrating that the change in the hmbR gene was responsible for the phenotypic switch. The switching rates from hmbR phase off to phase on were ∼5 × 10−4 in four serogroup C strains, 2 × 10−2 in the serogroup A isolate, and 7 × 10−6 in the serogroup B isolate.

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Tsang, Raymond S. W., and Wendell D. Zollinger. "Serological Specificities of Murine Hybridoma Monoclonal Antibodies against Neisseria meningitidis Serogroups B, C, Y, and W135 and Evaluation of Their Usefulness as Serogrouping Reagents by Indirect Whole-Cell Enzyme-Linked Immunosorbent Assay." Clinical Diagnostic Laboratory Immunology 12, no. 1 (January 2005): 152–56. http://dx.doi.org/10.1128/cdli.12.1.152-156.2005.

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ABSTRACT Murine hybridoma monoclonal antibodies (MAbs) were produced against the capsular antigens of serogroups B, C, Y, and W135 meningococci. Each serogroup-specific MAb reacted with the extracted capsular polysaccharide from its homologous serogroup only and did not react with capsules from the other three serogroups. The application of these MAbs for serogroup identification of meningococci was demonstrated by their abilities to correctly identify 183 clinical isolates of 185 meningococci recovered from individual invasive meningococcal disease (IMD) patients during routine surveillance in 2002. The remaining two meningococci were identified by PCR grouping as C in one case and Y in another, but neither isolate was positive by bacterial agglutination using rabbit antisera or by enzyme-linked immunosorbent assay using MAbs. The specificities of the anti-Y and anti-W135 MAbs were further assessed by tests with 37 serogroup W135 and 106 serogroup Y meningococci recovered from IMD cases during 1999 to 2001 and 2003. All 143 meningococci except one serogroup Y isolate were correctly identified by positive reactions with the corresponding MAbs that identified their homologous serogroups. The single serogroup Y isolate was received as nonagglutinable and tested as negative with both rabbit anti-Y antiserum and anti-Y MAb but was positive for the serogroup Y-specific siaD gene. The advantage of using MAbs for serogrouping of meningococci is discussed.

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Tyler, Shaun, and Raymond Tsang. "Genetic analysis of Canadian isolates of C:2a:P1.2,5 and B:2a:P1.2,5Neisseria meningitidisstrains belonging to the hypervirulent clone of ET-15." Canadian Journal of Microbiology 50, no. 6 (June 1, 2004): 433–43. http://dx.doi.org/10.1139/w04-024.

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Isolates of the hypervirulent Neisseria meningitidis clone ET-15 found to express the serogroup B antigen were investigated and compared with representative members of serogroup B and C isolates. Clonal-clustering methods clearly grouped the B:ET15 isolates with C:ET15 isolates, indicating the only major difference between the two groups was in the capsule expressed. The organization of the cps operon from the B:ET15 isolates was found to be consistent with typical serogroup B isolates and differed from serogroup C isolates only in the sialyl transferase gene present. This suggests that these strains arose via recombination of the sialyl transferase gene. Specific points of recombination could not be identified, however, the majority (64%) of the B:ET15 isolates contained a copy of pseudo-IS1106 downstream of the cps operon indicating the potential for a common ancestral origin. The combination of pulsed-field gel electrophoresis (PFGE) and sequence analysis of targeted regions of the cps operon permitted the differentiation of most B:ET15 isolates indicating that they likely arose from separate genetic events and do not represent the emergence and spread of a new clone. However, two isolates that appeared identical by all methods employed were temporally and geographically related although no epidemiological evidence is available indicating a link between these strains.Key words: Neisseria meningitidis, ET-15, cps operon, capsule switching, IS element.

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