Academic literature on the topic '4CMenB'
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Journal articles on the topic "4CMenB"
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Gönüllü, Erdem, Burcu Topçu, Naci Öner, Ahmet Soysal, and Metin Karaböcüoğlu. "Fever-Associated Supraventricular Tachycardia after 4CMenB Vaccination in an Infant." Case Reports in Pediatrics 2019 (September 22, 2019): 1–3. http://dx.doi.org/10.1155/2019/4591964.
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Meningococcal serogroup B vaccine 4CMenB (Bexsero) is a new four-component protein vaccine developed to prevent Neisseria meningitidis serogroup B infections. Case. We report a girl with fever and supraventricular tachycardia (SVT) 6–8 hours after the second dose of 4CMenB. SVT was unresponsive to the first dose of adenosine but terminated after the fourth dose of adenosine. During three months of follow-up, she was free of further SVT attacks. Conclusion. This is the first report of ECG-proven SVT after 4CMenB vaccination. Even if fever is coexistent, SVT should be considered after persistent tachycardia and 4CMenB vaccination.
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Kent, Alison, Kazim Beebeejaun, Serena Braccio, Seilesh Kadambari, Paul Clarke, Paul T. Heath, and Shamez Ladhani. "Safety of meningococcal group B vaccination in hospitalised premature infants." Archives of Disease in Childhood - Fetal and Neonatal Edition 104, no. 2 (April 10, 2018): F171—F175. http://dx.doi.org/10.1136/archdischild-2017-314152.
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ObjectivesTo assess the risk of significant adverse events in premature infants receiving the novel 4-component group B meningococcal vaccine (4CMenB) with their routine immunisations at 2 months of age.Participants, design and settingIn December 2015, Public Health England requested neonatal units across England to voluntarily participate in a national audit; 19 units agreed to participate. Anonymised questionnaires were completed for infants receiving 4CMenB alongside their routine immunisations. For comparison, a historical cohort of premature infants receiving their primary immunisations without 4CMenB or paracetamol prophylaxis was used.Main outcome measuresParacetamol use; temperature, cardiovascular, respiratory and neurological status before and after vaccination; and management and investigations postvaccination, including serum C reactive protein levels, infection screens and antibiotic use.ResultsComplete questionnaires were returned for 133 premature infants (<35 weeks’ gestation) who received their first dose of 4CMenB at 8 weeks of age, including 108 who received prophylactic paracetamol according to national recommendations. Overall, 7% (8/108) of infants receiving 4CMenB with paracetamol had fever (>38°C) after vaccination compared with 20% (5/25) of those receiving 4CMenB without paracetamol (P=0.06) and none of those in the historical cohort. There were no significant differences between cohorts in the proportion of infants with apnoea, bradycardia, desaturation and receiving respiratory support after vaccination.Conclusions4CMenB does not increase the risk of serious adverse events in hospitalised premature infants. This audit supports the current national recommendations to offer 4CMenB with other routine vaccinations and prophylactic paracetamol to premature infants at their chronological age.
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Marshall, Helen S., Prabha H. Andraweera, James Ward, John Kaldor, Ross Andrews, Kristine Macartney, Peter Richmond, et al. "An Observational Study to Assess the Effectiveness of 4CMenB against Meningococcal Disease and Carriage and Gonorrhea in Adolescents in the Northern Territory, Australia—Study Protocol." Vaccines 10, no. 2 (February 16, 2022): 309. http://dx.doi.org/10.3390/vaccines10020309.
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Invasive meningococcal disease (IMD) causes significant morbidity and mortality worldwide with serogroup B being the predominant serogroup in Australia and other countries for the past few decades. The licensed 4CMenB vaccine is effective in preventing meningococcal B disease. Emerging evidence suggests that although 4CMenB impact on carriage is limited, it may be effective against gonorrhoea due to genetic similarities between Neisseria meningitidis and Neisseria gonorrhoeae. This study protocol describes an observational study that will assess the effect of the 4CMenB vaccine against meningococcal carriage, IMD and gonorrhoea among adolescents in the Northern Territory (NT). All 14–19-year-olds residing in the NT with no contraindication for 4CMenB vaccine will be eligible to participate in this cohort study. Following consent, two doses of 4CMenB vaccine will be administered two months apart. An oropharyngeal swab will be collected at baseline and 12 months to detect pharyngeal carriage of Neisseria meningitidis by PCR. The main methodological approaches to assess the effect of 4CMenB involve a nested case control analysis and screening method to assess vaccine effectiveness and an Interrupted Time Series regression analysis to assess vaccine impact. Research ethics approvals have been obtained from Menzies and Central Australian Human Research Ethics Committees and the Western Australian Aboriginal Health Ethics Committee. Results will be provided in culturally appropriate formats for NT remote and regional communities and published in international peer reviewed journals. ClinicalTrials.gov Identifier: NCT04398849.
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Yamashiro, Hirotaka, Nora Cutcliffe, Simon Dobson, David Fisman, and Ronald Gold. "The Role of Pediatricians as Key Stakeholders in Influencing Immunization Policy Decisions for the Introduction of Meningitis B Vaccine in Canada: The Ontario Perspective." Canadian Journal of Infectious Diseases and Medical Microbiology 26, no. 4 (2015): 183–90. http://dx.doi.org/10.1155/2015/963940.
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As key stakeholders in immunization policy decisions, the Pediatricians of Ontario held an accredited conference on January 18, 2014, to discuss prevention of invasive meningococcal disease. Five key recommendations were put forth regarding immunization strategies to protect children from meningococcal serogroup B disease. The recently approved four-component meningococcal B (4CMenB) vaccine should be recommended and funded as part of Ontario’s routine immunization schedule and should also be mandated for school attendance. Public funding for 4CMenB immunization is justified based on current MenB epidemiology, vaccine coverage, cost effectiveness and acceptability, as well as legal, political and ethical considerations related to 4CMenB immunization, particularly because routine recommendations and funding are currently in place for vaccination against meningococcal serogroups that cause significantly less disease in Canada than MenB. Broadly, the goals are to assist individual practitioners in advocating the benefits of 4CMenB vaccination to parents, and to counterbalance recommendations from the National Advisory Committee on Immunization and the Canadian Paediatric Society.
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Kimura, Alan, Daniela Toneatto, Annett Kleinschmidt, Huajun Wang, and Peter Dull. "Immunogenicity and Safety of a Multicomponent Meningococcal Serogroup B Vaccine and a Quadrivalent Meningococcal CRM197Conjugate Vaccine against Serogroups A, C, W-135, and Y in Adults Who Are at Increased Risk for Occupational Exposure to Meningococcal Isolates." Clinical and Vaccine Immunology 18, no. 3 (December 22, 2010): 483–86. http://dx.doi.org/10.1128/cvi.00304-10.
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ABSTRACTLaboratory staff who work with meningococcal isolates are at increased risk for developing invasive disease relative to the general population. This was the first study of laboratory workers who received both a conjugate vaccine against meningococcal serogroups A, C, W-135, and Y (Men ACWY-CRM, Menveo) and an investigational multicomponent vaccine against serogroup B containing factor H binding protein, neisserial adhesin A,Neisseriaheparin binding antigen, and New Zealand strain outer membrane vesicles (4CMenB). Healthy adults (18 to 50 years of age) received three doses of 4CMenB at baseline, 2 months, and 6 months followed by a single dose of MenACWY-CRM 1 month later. Immunogenicity was assessed via serum bactericidal assay using human complement (hSBA) at 1 month postvaccination; solicited reactogenicity and adverse events were monitored. Fifty-four participants enrolled. Bactericidal immune responses were evident after each dose of 4CMenB, as assessed by hSBA geometric mean titers and percentages of subjects with hSBA titers of ≥4 against the test strains or a 4-fold rise in titer over baseline. At 1 month postvaccination, most MenACWY-CRM recipients had hSBA titers of ≥8 against serogroups A, C, W-135, and Y. Few participants discontinued due to an adverse event or vaccine reaction. Rates of solicited reactions were lower after MenACWY-CRM than after 4CMenB administration. Sequential administration of 4CMenB and MenACWY-CRM provided robust evidence of an immune response against serogroups A, B, C, W-135, and Y in laboratory workers routinely exposed to meningococcal isolates.
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Isitt, Catherine, Catherine A. Cosgrove, Mary Elizabeth Ramsay, and Shamez N. Ladhani. "Success of 4CMenB in preventing meningococcal disease: evidence from real-world experience." Archives of Disease in Childhood 105, no. 8 (February 6, 2020): 784–90. http://dx.doi.org/10.1136/archdischild-2019-318047.
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Meningococcal disease remains one of the most feared infectious diseases worldwide because of its sudden onset, rapid progression and high case fatality rates, while survivors are often left with severe long-term sequelae. Young children have the highest incidence of invasive meningococcal disease (IMD), and nearly all cases in the UK, as in most of Europe and many other industrialised countries, are due to group B meningococci (MenB). The licensure of a broad-coverage, recombinant protein-based MenB vaccine (4CMenB) in 2013 was, therefore, heralded a major breakthrough in the fight against IMD. This vaccine was, however, licensed on immunogenicity and reactogenicity studies only, raising uncertainties about field effectiveness, long-term safety and antibody persistence. In 2015, the UK became the first country to implement 4CMenB into the national infant immunisation schedule and, since then, several countries have followed suit. Seven years after licensure, a wealth of real-world data has emerged to confirm 4CMenB effectiveness, along with large-scale safety data, duration of protection in different age groups, successful strategies to reduce vaccine reactogenicity, impact on carriage in adolescents and the potential for 4CMenB to protect against other meningococcal serogroups and against gonorrhoea. A number of questions, however, remain unanswered, including the investigation and management of vaccine-associated fever in infants, as well as disease severity and assessment of breakthrough cases in immunised children. Increasing use of 4CMenB will provide answers in due course. We now have vaccines against all the major serogroups causing IMD worldwide. Next-generation and combination vaccines against multiple serogroups look very promising.
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Lucidarme, Jay, Stefanie Gilchrist, Lynne S. Newbold, Stephen J. Gray, Edward B. Kaczmarski, Lynne Richardson, Julia S. Bennett, Martin C. J. Maiden, Jamie Findlow, and Ray Borrow. "Genetic Distribution of Noncapsular Meningococcal Group B Vaccine Antigens in Neisseria lactamica." Clinical and Vaccine Immunology 20, no. 9 (June 26, 2013): 1360–69. http://dx.doi.org/10.1128/cvi.00090-13.
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ABSTRACTThe poor immunogenicity of the meningococcal serogroup B (MenB) capsule has led to the development of vaccines targeting subcapsular antigens, in particular the immunodominant and diverse outer membrane porin, PorA. These vaccines are largely strain specific; however, they offer limited protection against the diverse MenB-associated diseases observed in many industrialized nations. To broaden the scope of its protection, the multicomponent vaccine (4CMenB) incorporates a PorA-containing outer membrane vesicle (OMV) alongside relatively conserved recombinant protein components, including factor H-binding protein (fHbp),Neisseriaadhesin A (NadA), and neisserial heparin-binding antigen (NHBA). The expression of PorA is unique to meningococci (Neisseria meningitidis); however, many subcapsular antigens are shared with nonpathogenic members of the genusNeisseriathat also inhabit the nasopharynx. These organisms may elicit cross-protective immunity against meningococci and/or occupy a niche that might otherwise accommodate pathogens. The potential for 4CMenB responses to impact such species (and vice versa) was investigated by determining the genetic distribution of the primary 4CMenB antigens among diverse members of the common childhood commensal,Neisseria lactamica. All the isolates possessednhbabut were devoid offhbpandnadA. Thenhbaalleles were mainly distinct from but closely related to those observed among a representative panel of invasive MenB isolates from the same broad geographic region. We made similar findings for the immunogenic typing antigen, FetA, which constitutes a major part of the 4CMenB OMV. Thus, 4CMenB vaccine responses may impact or be impacted by nasopharyngeal carriage of commensal neisseriae. This highlights an area for further research and surveillance should the vaccine be routinely implemented.
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Nolan, Terry, Hartley Garfield, Anil Gupta, Murdo Ferguson, Helen Marshall, Diego D’Agostino, and Daniela Toneatto. "Persistence of Bactericidal Activity at 4 Years After 2 Primary Doses of a Recombinant, 4-Component, Meningococcal Serogroup B Vaccine (4CMenB) and Response to a Booster Dose in Adolescents and Young Adults." Open Forum Infectious Diseases 4, suppl_1 (2017): S322. http://dx.doi.org/10.1093/ofid/ofx163.757.
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Abstract Background This phase 3b, open label, controlled, multi-center, extension study (NCT02446743) assessed the persistence of bactericidal activity at 4 years post-primary vaccination with a recombinant, 4-component, meningococcal serogroup B vaccine (4CMenB) in adolescents who participated in the parent study NCT01423084 and their response to a booster dose, compared with that in vaccine-naïve healthy controls. Methods Adolescents and young adults previously primed with 4CMenB (2 doses; following a 0,1-month schedule) in study NCT01423084 (group 3B) and vaccine-naïve 15–22 year olds (group B0_1) were enrolled. Group 3B received a booster dose of 4CMenB at 4 years post-primary vaccination; group B0_1 received 2 catch-up doses of 4CMenB (following a 0,1-month schedule). Antibody persistence (primary objective) was evaluated at 4 years post-primary vaccination (in group 3B) vs. baseline (in group B0_1) using human serum bactericidal assay (hSBA), in terms of geometric mean titer (GMT) and percentage (%) of individuals with hSBA titer at least 4. Immune responses at 1 month after booster dose (in group 3B) vs. those at 1 month after first dose (in group B0_1) were also assessed. Results In group 3B, antibody levels declined from 1 month to 4 years post-primary vaccination against all antigens except NHBA, but were higher than in group B0_1 at baseline (Table), with a GMT ratio ≥1.3 and a difference in % of individuals with hSBA titer at least 4 of ≥9%. After one dose of 4CMenB (booster in 3B or first dose in B0_1), GMTs increased (≥4.6-fold in group 3B; ≥2.3-fold in group B0_1), and ≥94% of participants in group 3B and ≥41% of participants in group B0_1 had hSBA titer at least 4 (Table). Conclusion Antibody levels in adolescents and young adults primed with 4CMenB waned over time but were higher at 4 years post-primary vaccination than for vaccine-naïve individuals at baseline. A booster dose of 4CMenB in vaccine-primed individuals elicited higher immune responses than one dose of 4CMenB in vaccine-naïve individuals. The research was supported by GlaxoSmithKline Biologicals SA. Disclosures T. Nolan, GSK group of companies: Research Contractor and Scientific Advisor, Research grant. Pfizer: Research Contractor, Research grant. H. Garfield, Novartis/GSK group of companies: Investigator, Research support. A. Gupta, Novartis/GSK group of companies: Investigator, payment for research-related activities; M. Ferguson, GSK group of companies: Investigator, I receive salary from CRG. CRG has contracts with GSK. H. Marshall, GSK group of companies: Grant Investigator and Investigator, Research grant. Pfizer: Grant Investigator and Investigator, Research grant; sanofi pasteur: Grant Investigator, Research grant. Novavax: Investigator, Research grant. D. D’Agostino, GSK group of companies: Consultant, Consulting fee. D. Toneatto, GSK group of companies: Employee, Salary.
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Azzari, Chiara, Maria Moriondo, Francesco Nieddu, Valentina Guarnieri, Lorenzo Lodi, Clementina Canessa, Giuseppe Indolfi, et al. "Effectiveness and Impact of the 4CMenB Vaccine against Group B Meningococcal Disease in Two Italian Regions Using Different Vaccination Schedules: A Five-Year Retrospective Observational Study (2014–2018)." Vaccines 8, no. 3 (August 22, 2020): 469. http://dx.doi.org/10.3390/vaccines8030469.
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Background: A few years after the introduction in Italy of a four-component anti-meningococcal B vaccine (4CMenB), we evaluated the effectiveness and impact of vaccination in two regions using different schedules (2, 4, 6, 12 months in Tuscany vs. 7, 9, 15 months in Veneto) through an observational retrospective study. Methods: Vaccination started in 2014 in Tuscany and in 2015 in Veneto; the data collected referred to the period 2006–2018 for Tuscany and 2007–2018 for Veneto. Cases of invasive meningococcal disease due to N. Meningitidis B were identified by culture and/or real-time PCR. Results: In Tuscany, pre-vaccine incidence was 1.96 (95% CL 1.52; 2.40) and dropped to 0.62 (95% CL 0.60; 0.64) in the post-4CMenB era. Evaluating only vaccinated children, post-4CMenB incidence was 0.12 (95% CL 0.08; 0.15). In Veneto pre-vaccine incidence was 1.94 (95% CL 1.92; 1.96) and dropped to 1.34 (95% CL 1.31; 1.38) in the post-4CMenB era. In the vaccinated population, MenB incidence was 0.53 (95% CL 0.50; 0.56). Vaccine effectiveness was 93.6% (95% CL 55.4; 99.1) in Tuscany and 91.0% (95% CL 59.9; 97.9) in Veneto, with mean vaccine coverages of 83.9% and 81.7%, respectively. The overall impact (evaluating both vaccinated and unvaccinated children) was 0.68 (95% CL 0.10; 0.89) in Tuscany and 0.31 (95% CL −0.56; 0.69) in Veneto; the total impact (evaluating only vaccinated children) was 0.94 (95% CL 0.56; 0.99) and 0.90 (95% CL 0.57; 0.97), respectively. The relative case reduction (RCR) was 65% in Tuscany and 31% in Veneto. Considering the vaccinated population, the RCR was equal to 91% and 80%, respectively. Conclusion: In conclusion, 4CMenB appears to have a very high effectiveness in Italy; the impact of vaccination appears greater where the immunization program is started early.
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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.
Dissertations / Theses on the topic "4CMenB"
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Viviani, Viola <1992>. "Dissection of the protective response elicited by the DOMV component of the 4CMenB vaccine." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amsdottorato.unibo.it/9779/1/Viviani_Viola_tesi.pdf.
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Neisseria meningitidis serogroup B is the major etiological agent of meningitis and life-threatening sepsis, against which two vaccines are licensed. The 4CMenB vaccine is composed of three major protein antigens (fHbp, NHBA and NadA) and detergent-extracted outer membrane vesicles (DOMV) from the NZ98/254 strain. DOMV are safe, immunogenic and able to raise bactericidal antibodies, mainly attributed to the immunodominant PorA protein. Nevertheless, DOMV offer a complex reservoir of potentially immunogenic proteins, whose relative contribution in protection is still poorly characterized.
By testing antisera from vaccinated infants in serum bactericidal assay, we observed that the addition of DOMV in the vaccine formulation enhanced breadth of coverage compared to recombinant proteins alone against a panel of 11 meningococcal strains mismatched for the vaccine antigens. To unravel the DOMV components involved in such protection, 30 DOMV antigens were cloned and expressed in Escherichia coli as recombinant proteins and/or in vesicles to maintain their native conformation. Samples obtained were both included in tailor-made protein-microarrays to immunoprofile the antibody repertoire raised by DOMV-containing formulations and were individually used for mouse immunization studies to assess their ability to induce bactericidal antibodies.
The protein-array immunosignature of mouse DOMV/4CMenB antisera unveiled a subset of 8 DOMV-reactive proteins potentially responsible for the additional protective responses. The antisera derived from mouse immunizations showed high levels of antibodies and recognized the corresponding antigen across different meningococcal strains. Among the protein-array reactive antigens, OpcA, NspA and PorB induced antibodies able to kill 10 of the 11 genetically diverse meningococcal strains and the specificity of the protective role of OpcA and PorB was also confirmed in 4CMenB infant vaccinee sera.
In conclusion, we identified additional PorA-independent antigens within DOMV involved in broadening the coverage of 4CMenB, thus supporting the key role played by vesicles in this multivalent formulation.
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Jördens, Markus Sebastian [Verfasser], and Ulrich [Gutachter] Vogel. "Einfluss des Komplementsystems und der neuartigen Meningokokken-Vakzine 4CMenB auf cnl-Meningokokken / Markus Sebastian Jördens ; Gutachter: Ulrich Vogel." Würzburg : Universität Würzburg, 2017. http://d-nb.info/1130587975/34.
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NDONI, ENEA. "Characterization of the immune response and cross protection activity elicited by the Neisserial Heparin Binding Antigen (NHBA), a component of the 4CMenB vaccine." Doctoral thesis, Università di Siena, 2017. http://hdl.handle.net/11365/1011542.
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Invasive disease caused by capsular group B Neisseria meningitidis (MenB) is life threating disease causing hundred thousands of deaths every year, still remaining an unmet medical need in many countries. Although disease can be observed at all age groups, infants and adolescents are the most at risk populations showing the highest incidence in case numbers. Since the MenB capsule was not-immunogenic the development of a MenB vaccine which makes the use of other antigens becomes necessary. 4CMenB is a multicomponent vaccine against serogroup B N. meningitidis composed by three major protein antigens, factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisserial adhesin A (NadA), combined with outer membrane vesicles (OMVs) from the New-Zealand epidemic strain (NZ98/254). Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein expressed by all N. meningitidis strains analyzed so far and is composed of two major domains, a highly variable amino-terminal (N-term) domain which anchors the protein on the bacterial outer membrane through the lipobox motif, and a highly conserved carboxyl-terminal (C-term) domain. These domains are separated by a short and quite conserved Arginine-rich (Arg-rich) motif which has been reported to be involved in different mechanisms that mediate meningococci adhesion, infection and survival within the host’s blood stream. NHBA is susceptible to cleavage by NalP, a bacterial protease which has its cleavage site upstream of the arginine region. Moreover human proteases such as human lactoferrin (hLf) and kallikrein are able to process NHBA downstream the the Arg-rich region. Both bacterial and human proteases-mediated cleavage releases the C-term of NHBA in the supernatant, while the N-term of the protein remains anchored on the bacterial surface. NalP cleavage did not impact SBA titers elicited by anti-NHBA antibodies but little is known about the impact that host’s proteases have on bactericidal titers. Based on sequence analysis it has been reported that NHBA has two major alleles, the so called “short” and “long” variants, which differentiate by the presence or absence of a 190 bp long fragment. Despite its sequence variability, NHBA is able to induce a robust and broad immune response against meningococcal strains expressing vaccine homologous and heterologous variants. Although anti-NHBA antibodies are able to induce bacterial killing when tested in serum bactericidal activity assay (SBA), the regions involved in eliciting cross protective immune response remain still unknown. Aims of this study were to use monoclonal antibodies (mAbs) raised against the NHBA vaccine variant peptide 2 (NHBAp2) to (i) map the NHBA regions involved in eliciting the functional response, (ii) test their ability to induce cross protection against strains expressing epidemiologically relevant homologous and heterologous NHBA variants, and (iii) investigate the molecular mechanism of NHBA-mediated bactericidal activity. To this end we used a panel of anti-NHBA mAbs selected to recognize different regions of the protein. Our results showed that only anti-N-term mAbs were able to induce killing of bacterial strains expressing the homologous NHBAp2 and closely related heterologous NHBA variants. Synergy between monoclonal antibodies targeting the N-term and the C-term of NHBA resulted in a significant increase of bactericidal titers but cross protection remained restricted to closely phylogenetic NHBA variants. Anti C-term mAbs were not able to induce SBA activity when tested individually, but surprisingly they became bactericidal when tested in combination. Moreover they were able to induce full cross protection against a panel of strains expressing phylogenetically distant heterologous NHBA variants.
Our results suggest that the partial release of the NHBA C-terminal portion upon NalP and serum proteases could explain why anti-C-term mAbs are not able to induce complement mediated bactericidal killing when tested individually. However, the simultaneous binding of C-term mapping mAbs on the same NHBA molecule can induce the formation of a very stable ternary complex that probably allows a more efficient C1q engagement and C3 deposition, thus leading to the observed co-operative bactericidal activity. These results suggest that synergy between anti-NHBA antibodies is at the basis of the mechanism of NHBA-induced bactericidal activity, which could explain the robust and cross-protective immune response elicited by anti-NHBA polyclonal antibodies following immunization. Collectively, the body of experimental data suggests that both domains of NHBA are required to elicit complement mediated bactericidal activity against strains expressing the vaccine homologous and heterologous NHBA variants.
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Jördens, Markus Sebastian. "Einfluss des Komplementsystems und der neuartigen Meningokokken-Vakzine 4CMenB auf cnl-Meningokokken." Doctoral thesis, 2016. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-147071.
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In dieser Arbeit wurden verschiedene Vakzine-relevante Oberflächenantigene von cnl-Meningokokken typisiert und die Interaktion von cnl-Meningokokken mit dem Komplementsystem, v.a. mit dessen Hauptregulatoren fH und C4bp, analysiert. Mit den gewonnenen Daten sollten Schlussfolgerungen bzgl. der erwarteten Wirkung von 4CMenB, einem 2013 in Deutschland eingeführten und auf Meningokokken der Serogruppe B abzielenden Impfstoff, auf cnl-Meningokokken gezogen werden. Des Weiteren sollte die Interaktion der natürlicherweise unbekapselten cnl-Meningokokken, die als apathogen und möglicherweise günstig für die Entwicklung einer natürlichen Immunität eingeschätzt werden, untersucht werden. Eine Auswahl von cnl-Meningokokken-Stämmen, die die genetische Variabilität dieser Bakterienpopulation abbilden, wurde mittels PCR (porA, porB, fetA, opc, fHbp, nhba und nadA) oder Western Blot-Analyse (Opc) typisiert. Hierbei konnte eine deutliche Assoziation einzelner Allele zu klonalen Komplexen gezeigt werden. Allerdings lässt die Analyse bezweifeln, dass cnl-Meningokokken durch Bexsero-induzierte Antikörper erkannt werden, da ihr Antigenmuster stark von den Vakzineantigenen abweicht. Unklarheit herrscht lediglich bzgl. des Antigens NhbA. In der Folge wurde die fH- und C4bp-Bindung bei cnl-Meningokokken mittels Durchflusszytometrie untersucht. Es konnte beobachtet werden, dass im Vergleich zu fH bzw. C4bp bindenden Kontrollstämmen die Bindung der Hauptregulatoren des Komplementsystems an cnl-Meningokokken sehr gering ist. Weiterhin konnte gezeigt werden, dass cnl-Meningokokken eine sehr geringe Serumresistenz in vitro haben, was ebenfalls für eine schwache Akquirierung der Komplementregulatoren spricht. Dieser Befund unterstreicht die apathogene Natur der Bakterien. Er zeigt aber auch, dass mit herkömmlichen Methoden wie dem Serumbakterizidietest, der bei bekapselten Stämmen angewendet wird, funktionelle Aussagen bzgl. der Wirkung bakterizider Antikörper, die durch Impfstoffe auf Proteinbasis induziert werden, nur schwer zu tätigen sein werden. Sehr geringe Komplementmengen müssten eingesetzt werden oder alternative Verfahren wie die Opsonophagozytose Anwendung findenIn this study we typed Vaccine-relevant outer membrane antigens of cnl-meningococci. Furthermore we analysed the interactions of cnl-meningococci with the complement System, especially with the main Regulators factor H and C4bp. The data should help to estimate the impact of 4CMenB, a vaccine against meningococci of serogroup B which was introduced to the german market in 2013, on cnl-meningococci. In addition we examined the interactions of the complemet system with cnl-meningocicci, which are supposed to be apathogen and maybe beneficial for the development of natural immunity. A selection of cnl-meningococci which represent the genetical variability of that bacteria Population was typed for outer membrane Proteins by PCR (porA, porB, fetA, opc, fHbp, nhba, nadA) or western-blot (opc). A close assotiation of allels to clonal complexes could be shown. It is likely that cnl-meningococci are not detected by Bexsero-induced antibodies as their antigen pattern differs from the vaccine Antigens. The only Antigen which ould be detected is NhbA. Factor H and C4bp-binding to cnl-meningococci was examined using flow cytometry Analysis. The binding of fH or C4bp to cnl-meningococci was significantly lower as to fH- or C4cb-binding controll strains. Furthermore serum resistance of cnl-meningococci in vitro is low, which is also an indicator for weak binding of Regulators of the complement System. This finding underlines the apathogen nature of cnl-meningococci. It also indicates the problem of serum bactericidity tests to assess the impact of antibodies induced by protein based vaccines
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McMillan, Mark. "Impact of meningococcal vaccines on carriage and disease." Thesis, 2021. https://hdl.handle.net/2440/132672.
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South Australia (SA) has one of the highest notification rates of invasive meningococcal disease (IMD) and, unlike other jurisdictions, serogroup B meningococci has been the predominant cause over the last two decades. Asymptomatic pharyngeal carriage is substantially higher in adolescents and young adults than other age groups. Adolescents and young adults are the critical population in the transmission of meningococcal bacterium and the primary target group for herd protection strategies. In 2013, 4CMenB vaccine was licensed for use by the Therapeutic Goods Administration in Australia against serogroup B disease. However, 4CMenB is not included as part of the National Immunisation Program for all children, or adolescents. This decision was in part based on the lack of information about the extent and duration of a herd protection effect from meningococcal B vaccines. As meningococcal B vaccines have been developed with novel technologies, herd protection effects seen with conjugate meningococcal vaccines cannot be guaranteed, and the evidence for their effectiveness against IMD is limited. This is the first-ever study assessing meningococcal carriage in Australian adolescents. The overarching aim of this thesis was to establish if the 4CMenB vaccine is effective in reducing meningococcal carriage. Secondary aims were to establish the vaccine impact against disease in adolescents, as well as carriage prevalence, and risk factors for carriage. The principal findings were: 1. Carriage prevalence of N. meningitidis increased in each school year, from 2.2 % in year 10, 3.3% in year 11, and 5.5% in year 12 students, to 9.1% in school leavers (mean age 18.5 years). 2. In the largest randomised interventional meningococcal carriage study to date: a. 4CMenB had no impact on carriage of disease-causing meningococci in adolescents 12 months after vaccination. b. 4CMenB had no effect on carriage density in those with meningococcal carriage at 12 months. c. Higher meningococcal carriage density was associated with a greater risk of carriage 12 months later. 3. Following the state-wide RCT, there were approximately 15 (95% confidence interval (CI), 3 to 19) less serogroup B IMD cases in the post-vaccination period (June 2017-2019) than the number of predicted cases. 4. Year of schooling (age), having a current respiratory infection, smoking cigarettes or water-pipe, attending pubs/clubs, kissing intimately, drinking alcohol, and not being of Asian ethnicity were all associated with an increased risk of meningococcal carriage. 5. The state-wide RCT led to a 35% absolute increase in 4CMenB vaccine coverage in school leavers from 2018 to 2019, but this did not correspond with a reduction in meningococcal carriage between 2018 and 2019. 6. Meta-analysis showed that meningococcal conjugate C, ACWY, as well as outer membrane vesicle vaccines are effective at reducing IMD. Meningococcal B vaccines did not reduce group B meningococcal carriage. In conclusion, 4CMenB immunisation programs should focus on direct (individual) protection for groups at greatest risk of meningococcal disease, rather than the potential for herd protection. The 4CMenB vaccine demonstrated that it provides significant reduction in group B IMD in adolescents following immunisation of high school students, supporting its use in adolescents.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2021
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花麒昌. "整合消費者行為模式與服務代理人之網路購物輔助系統." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/4cmez6.
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碩士國立清華大學
工業工程與工程管理學系
92
Due to the rapidly growing internet commercial activities, many businesses have been making their own e-Business websites. They might hope these websites could serve their potential consumers with sufficient products and service information. Unfortunately, finding information from separate websites is time-consuming for consumers, not to mention the disturbance of integrating all the information and evaluating them. Customers often lose their patience and desire of purchasing products in this process, which frustrated them. In the domain of e-Business, researchers have suggested that businesses should have “virtual agents” serve in the shopping websites for customers. This is because the agent could help customers in gathering substantial product information, searching available products, giving choice suggestions, assisting purchasing processes, and providing after purchase services. The agent is expected to increase consumers’ desire and satisfaction when they are purchasing on Internet. In this study, a virtual agent system was established based on the consumers’ need in searching, selecting and evaluating the products in the consumer behavior model. Mental load and time for purchasing were two chosen indicators, and both subjective and objective measures were used to evaluate the effect. The functions of agent include supplying the consumers with integrated product information, purchasing suggestions according to consumers’ budget and preference, buying process assistance, and after purchase service. More satisfied performance with indicators is expected when using the agent. The result certifies this hypothesis. It is concluded that virtual agent in the study is indeed helpful in the purchasing process and is of high potential for e-business.
Book chapters on the topic "4CMenB"
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Boccadifuoco, Giuseppe, Brunella Brunelli, Elena Mori, Mauro Agnusdei, Claudia Gianfaldoni, and Marzia Monica Giuliani. "Meningococcal Antigen Typing System (MATS): A Tool to Estimate Global Coverage for 4CMenB, a Multicomponent Meningococcal B Vaccine." In Methods in Molecular Biology, 205–15. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9202-7_14.
Full textConference papers on the topic "4CMenB"
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Franco, Nathércia, Aline Azevedo, and Ivano Filippis. "Distribuição dos antígenos de superfície incluídos na vacina meningocócica 4CMenB em amostras brasileiras no período de 2010 a 2015." In VI Seminário Anual Científico e Tecnológico. Instituto de Tecnologia em Imunobiológicos, 2018. http://dx.doi.org/10.35259/isi.sact.2018_27108.
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Channon-Wells, Samuel, Emily Tough, Neda So, Daniel O’Connor, and Matthew Snape. "269 Differentiating vaccine reactions from invasive bacterial infections in infants presenting to the emergency department in the 4CMenB era: a retrospective descriptive comparison." In Royal College of Paediatrics and Child Health, Abstracts of the RCPCH Conference, Liverpool, 28–30 June 2022. BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health, 2022. http://dx.doi.org/10.1136/archdischild-2022-rcpch.9.
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