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Keywords = Neisseria meningitidis serogroup A

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15 pages, 1351 KiB  
Article
Epidemiology of Bacterial Meningitis in the Lombardy Region, Italy, from 2014 to 2024: An Observational, Retrospective Study
by Maria Francesca Liporace, Federica Salari, Beatrice Silvia Orena, Michela Piccoli, Elena Tomassini, Luigi Vezzosi, Gabriele Del Castillo, Laura Daprai, Danilo Cereda, Claudia Alteri and Annapaola Callegaro
Microorganisms 2025, 13(8), 1733; https://doi.org/10.3390/microorganisms13081733 - 24 Jul 2025
Viewed by 393
Abstract
Bacterial meningitis remains a critical public health issue globally due to its high morbidity and mortality. Understanding regional epidemiological trends is essential to inform vaccination strategies and public health interventions. This observational, retrospective study analyzed cerebrospinal fluid (CSF) isolates collected from 731 confirmed [...] Read more.
Bacterial meningitis remains a critical public health issue globally due to its high morbidity and mortality. Understanding regional epidemiological trends is essential to inform vaccination strategies and public health interventions. This observational, retrospective study analyzed cerebrospinal fluid (CSF) isolates collected from 731 confirmed cases of bacterial meningitis between 2014 and 2024 in Lombardy, Italy. Pathogen identification and serotyping of Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), and Haemophilus influenzae (HI) were conducted using culture-based and molecular techniques. Trends were assessed across age groups and time using Kruskal–Wallis and chi-square tests. Results: SP was the predominant pathogen (78.4%), followed by NM (13.0%) and HI (8.6%). Significant temporal variation was observed for SP and NM, while HI trends remained stable. The impact of COVID-19-related restrictions was evident in a reduction in cases during 2020–2021. SP serotypes 3 and 8, HI non-typeable strains, and NM serogroup B were most frequent. No major shifts in serotype distribution were observed. Long-term surveillance data from Lombardy underscore the dominance of vaccine-targeted serotypes, ongoing circulation of resilient clones, and post-pandemic epidemiological shifts. These findings support continuous surveillance and inform vaccine strategy adjustments at the regional and national levels. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Bacterial Infection)
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63 pages, 6750 KiB  
Review
Synthesis and Immunogenicity of Pseudo-Oligosaccharides Structurally Related to Repeating Units of Capsular Phosphoglycans of Human Pathogens
by Elena A. Khatuntseva, Anastasia A. Kamneva, Dmitry V. Yashunsky and Nikolay E. Nifantiev
Molecules 2025, 30(15), 3068; https://doi.org/10.3390/molecules30153068 - 22 Jul 2025
Viewed by 386
Abstract
This review focuses on the synthesis of spacer-armed phosphooligosaccharides structurally related to the capsular phosphoglycans of pathogenic bacteria, including the Haemophilus influenzae serotypes a, b, c, and f, Neisseria meningitidis serogroups a and x, the Streptococcus pneumoniae serotypes 6a, 6b, 6c, 6f, 19a, [...] Read more.
This review focuses on the synthesis of spacer-armed phosphooligosaccharides structurally related to the capsular phosphoglycans of pathogenic bacteria, including the Haemophilus influenzae serotypes a, b, c, and f, Neisseria meningitidis serogroups a and x, the Streptococcus pneumoniae serotypes 6a, 6b, 6c, 6f, 19a, and 19f, and the Campylobacter jejuni serotype HS:53, strain RM1221, in which the phosphodiester linkage is a structural component of a phosphoglycan backbone. Also, in this review, we summarize the current knowledge on the preparation and immunogenicity of neoglycoconjugates based on synthetic phosphooligosaccharides. The discussed data helps evaluate the prospects for the development of conjugate vaccines on the basis of synthetic phosphooligosaccharide antigens. Full article
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12 pages, 475 KiB  
Review
Meningococcal B Vaccines as a Paradigm of Safe and Effective Vaccines for Children
by Maribel Gonzalez Tome, Rosa Gonzalez-Quevedo, Maria Escudeiro dos Santos, Hans Juergen Dornbusch, Sabine Straus and Emer Cooke
Vaccines 2025, 13(7), 770; https://doi.org/10.3390/vaccines13070770 - 21 Jul 2025
Viewed by 525
Abstract
Background: Neisseria meningitidis B is one of the main causative pathogens of meningitis and other forms of severe meningococcal disease. In the past decade, meningococcal B vaccines have been developed to address this infection and its sequelae. Objective: This article aims to present [...] Read more.
Background: Neisseria meningitidis B is one of the main causative pathogens of meningitis and other forms of severe meningococcal disease. In the past decade, meningococcal B vaccines have been developed to address this infection and its sequelae. Objective: This article aims to present an example of how the EU regulatory framework allowed the early authorisation of two life-saving vaccines initially based on immunogenicity surrogates of clinical evidence. This was subsequently followed by post-marketing surveillance providing real-world evidence to support their safety profile and impact on the paediatric population in the EU. Methods: We review the evidence supporting the initial regulatory approval of the vaccines, the confirmatory data demonstrating vaccine effectiveness post-authorisation, and the real-world impact of these vaccines on the paediatric population. Results: Two vaccines were approved in the EU for active immunisation to prevent IMD caused by MenB (4CMenB in 2013 and MenB-fHBP in 2017). Both marketing authorisations were based on immunogenicity data (efficacy studies were not feasible due to the rarity of the disease) and safety data generated from pre-authorisation studies. Additional pharmacovigilance activities to further investigate the safety profile and effectiveness studies were requested to be conducted after approval. Both the effectiveness and safety profile of the vaccines were confirmed by these data. Conclusions: This paper illustrates that the EU medicines regulatory framework and safety monitoring system are robust. By supplementing the initial evidence with post-authorisation studies, further effectiveness and safety data enabled regulators to confirm the positive benefit–risk of the vaccines without delaying their access to the people who need them. Full article
(This article belongs to the Special Issue Vaccination and Public Health in the 21st Century)
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20 pages, 2293 KiB  
Article
An Evaluation of the Safety, Immunogenicity, and Protective Efficacy of a Combined Diphtheria–Tetanus–Acellular Pertussis, Haemophilus influenzae Type b, and ACYW135 Meningococcal Conjugate Vaccine in Murine and Rat Models
by Xiuwen Sui, Zhujun Shao, Yuanyuan Ji, Hairui Wang, Qingfu Xu, Bochao Wei, Zhuojun Duan, Chang Wang, Ying Yang, Jiayu Zhao and Tao Zhu
Vaccines 2025, 13(7), 724; https://doi.org/10.3390/vaccines13070724 - 3 Jul 2025
Viewed by 579
Abstract
Background: The combined diphtheria–tetanus–acellular pertussis (three-component), Haemophilus influenzae type b (Hib, conjugate), and ACYW135 meningococcal (conjugate) vaccine (DTaP-Hib-MCV4) offers a promising alternative to single-component vaccines, potentially simplifying immunization schedules and improving vaccination coverage. Methods: We evaluated the safety, immunogenicity, and protective [...] Read more.
Background: The combined diphtheria–tetanus–acellular pertussis (three-component), Haemophilus influenzae type b (Hib, conjugate), and ACYW135 meningococcal (conjugate) vaccine (DTaP-Hib-MCV4) offers a promising alternative to single-component vaccines, potentially simplifying immunization schedules and improving vaccination coverage. Methods: We evaluated the safety, immunogenicity, and protective efficacy of DTaP-Hib-MCV4 in animal models. Acute and long-term toxicity studies were conducted in Sprague-Dawley (SD) rats with equal numbers of male and female animals. Immunogenicity was assessed in female NIH mice and SD rats using a three-dose regimen at 14-day intervals. Orbital blood was collected 14 days post-immunization to measure IgG titers against pertussis, diphtheria, tetanus, Hib, and meningococcal antigens. The protective efficacy was determined using potency tests for the pertussis, diphtheria, and tetanus components; passive protection studies for Hib; and serum bactericidal antibody (SBA) titers against A/C/Y/W135 meningococcal serogroups. Results: Acute and repeated-dose toxicity studies in SD rats showed no signs of abnormal toxicity or irritation at either high (three doses/rat) or low (one dose/rat) doses levels. The no-observed-adverse-effect level (NOAEL) for DTaP-Hib-MCV4 was established at three doses/rat after 8 weeks of repeated intramuscular administration and a 4-week recovery period. Specific IgG antibodies against all the vaccine components were detected in animal sera at both one and three doses/rat, with no evidence of immunotoxicity. Following two-dose primary immunization in murine models, the combined vaccine elicited robust antigen-specific antibody responses, with geometric mean titers (GMTs) as follows: 1,280,000 for pertussis toxin (PT); 761,093 for filamentous hemagglutinin (FHA); 1,159,326 for pertactin (PRN); 1,659,955 for diphtheria toxoid (DT); 1,522,185 for tetanus toxoid (TT); 99 for Haemophilus influenzae type b (Hib); and 25,600, 33,199, 8300, and 9051 for serogroups A, C, Y, and W135 of Neisseria meningitidis, respectively. In the rat models, three-dose primary immunization also elicited robust antigen-specific antibody responses. Protection studies demonstrated efficacy against pertussis, tetanus toxin, and diphtheria toxin challenges. In the Hib challenge study, none of the 10 animals given anti-DTaP-Hib-MCV4 antiserum developed bacteremia after the live Hib challenge (vs. 5814/0.1 mL in the negative control, p < 0.001). In addition, the SBA titers against meningococcal serogroups exceeded the protective threshold (≥1:8) in 92.2% of the immunized mice and 100% of the immunized rats. Crucially, the combined vaccine induced potent immune responses and protective efficacy, with antibody levels and protection against each component antigen comparable to or greater than those of the individual components: DTaP, Hib, and MCV4. Conclusions: These findings demonstrate that the DTaP-Hib-MCV4 combined vaccine is both safe and immunogenic, supporting its potential as a viable alternative to individual vaccines. This combined vaccine may streamline immunization programs and enhance vaccination coverage. Full article
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12 pages, 668 KiB  
Article
Troubled Times, Changing Tides: A Seroprevalence Study on Meningococcal Immunity in France Between 2016 and 2024
by Samy Taha, Aude Terrade, Oumar Doucoure, Ala-Eddine Deghmane and Muhamed-Kheir Taha
Vaccines 2025, 13(6), 647; https://doi.org/10.3390/vaccines13060647 - 16 Jun 2025
Viewed by 536
Abstract
Background/Objectives: In France, non-pharmaceutical interventions (NPIs) implemented to control COVID-19 led to a significant decline in invasive meningococcal disease (IMD) cases. However, a rebound in cases, particularly for serogroups W and Y, was observed after the gradual lifting of NPIs, raising questions about [...] Read more.
Background/Objectives: In France, non-pharmaceutical interventions (NPIs) implemented to control COVID-19 led to a significant decline in invasive meningococcal disease (IMD) cases. However, a rebound in cases, particularly for serogroups W and Y, was observed after the gradual lifting of NPIs, raising questions about an “immunity gap” due to reduced circulation of the bacteria. During the study period, vaccination against MenC was mandatory from 2018, and vaccination against MenB has been recommended since 2022. Methods: We conducted a retrospective seroepidemiological study using 166 normal sera collected between 2016 and 2024. Anti-Neisseria meningitidis IgG levels were quantified by ELISA using purified capsular polysaccharides for serogroups B, C, W, Y, and X. Samples were categorized into three periods: pre-NPIs (n = 72), during NPIs (n = 33), and post-NPIs (n = 61). Statistical comparisons were performed using Kruskal–Wallis tests for non-parametric data. Results: Our results show a significant decline in anti-serogroup B IgG antibody levels after the lifting of NPIs (p < 0.0001) in line with reduced circulation. Anti-serogroup C IgG antibody levels increased incrementally (p = 0.0003), particularly in those aged 1–4 years, likely reflecting a catch-up in anti-meningococcal C vaccination coverage. Anti-serogroup W IgG antibody levels remained stable, suggesting sustained circulation, but shifted to young children in the post-NPI period, potentially due to a genotypic shift. Anti-serogroup Y IgG antibody levels transiently increased significantly (p < 0.0001) during the NPI period but then decreased back after their lifting. Anti-serogroup X IgG antibody levels remained stable, consistent with its low prevalence and the absence of targeted vaccination. Full article
(This article belongs to the Section Vaccines against Tropical and other Infectious Diseases)
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13 pages, 230 KiB  
Article
Genetic and Antigenic Diversity of Neisseria meningitidis Serogroup B Strains in Vietnam
by Trieu Phi Long, Vo Viet Cuong, Bui Thi Lan Anh, Trinh Van Toan, Vu Thi Loan, Pham Viet Hung, Le Thi Lan Anh, Nguyen Ngoc Tan, Luong Thi Mo, Le Van Khanh and Hoang Van Tong
Pathogens 2025, 14(5), 487; https://doi.org/10.3390/pathogens14050487 - 15 May 2025
Viewed by 1020
Abstract
Background: Neisseria meningitidis (N. meningitidis) is a leading cause of acute meningitis and is classified into 13 serogroups, six of which are predominantly associated with invasive meningococcal disease. This study aimed to investigate the genotype, subgenotype, and antigenic profiles of N. [...] Read more.
Background: Neisseria meningitidis (N. meningitidis) is a leading cause of acute meningitis and is classified into 13 serogroups, six of which are predominantly associated with invasive meningococcal disease. This study aimed to investigate the genotype, subgenotype, and antigenic profiles of N. meningitidis serogroup B strains isolated in Vietnam. Methods: Genotyping was performed on 106 N. meningitidis strains isolated from clinical samples from Vietnamese patients and nasopharyngeal swabs of healthy adolescents between 2019 and 2024. The genetic profiles, including the porA, porB, fetA, fHbp, abcZ, adk, aroE, fumC, gdh, pdhC, and pgm genes, were analyzed using Sanger sequencing and bioinformatic methods. Results: We found that 84.9% of the strains carried VR3 families 36 or 35-1, with VR1, VR2, and VR3 families 22-25, 14, and 36 being the most prevalent. Among the 106 serogroup B isolates, 20 variants of the porB allele 3 were identified, with porB 3-1212 being the most frequent (30.2%). Dominant PorB variable loops included L1.6, L4.5, L5.7, L6.6, and L7.13. fHbp variant group 2 was predominant (104/106 strains), and 12 FetA allele variants were identified, with F1-7 being the most common (47.2%). Three clonal complexes were identified, and clonal complex ST-32 was the most predominant. Fifty-five strains (51.9%) belonged to sequence types that have not yet been assigned to any clonal complexes, and 15 strains (14.1%) with allelic profiles were not assigned to STs. The 3-253 and 3-1212 alleles of porB, the F1-7 variant of FetA, the ST-44 and ST-1576 sequence types, and the ST-41/44 complex were observed more frequently in patients compared to asymptomatic carriers, suggesting their association with more virulence. Conclusions: This study showed a high genetic and antigenic diversity of N. meningitidis serogroup B isolates in Vietnam, with VR3 family 36 most common and porB 3-1212 as the predominant allele. fHbp variant group 2 and FetA allele F1-7 were most frequent. ST-32 was the dominant clonal complex, though many strains remained unassigned, highlighting the need for ongoing molecular surveillance. Full article
12 pages, 482 KiB  
Article
Invasive Meningococcal Disease in Children: Outcomes and Risk Factors for Sequelae and Fatal Cases in Greece
by Panagiotis Poulikakos, Dimitrios Kapnisis, Athanasia Xirogianni, Irini Liakou, Maria Tsolia, Athanasios Michos, Elpis Mantadakis, Vassiliki Papaevangelou, Andreas Iliadis, Despoina Gkentzi, Stavroula Kostaridou Nikolopoulou, Maria Sdougka, Konstantina Charisi, Athanasios Bangeas, Evangelia Farmaki and Georgina Tzanakaki
Microorganisms 2025, 13(4), 705; https://doi.org/10.3390/microorganisms13040705 - 21 Mar 2025
Cited by 1 | Viewed by 832
Abstract
Invasive meningococcal disease (IMD) remains a major public health challenge due to its rapid progression, which may lead to severe sequelae or death in children and adolescents. Published data on IMD sequelae are limited in Greece and many EU countries. In the present [...] Read more.
Invasive meningococcal disease (IMD) remains a major public health challenge due to its rapid progression, which may lead to severe sequelae or death in children and adolescents. Published data on IMD sequelae are limited in Greece and many EU countries. In the present study, patients under 16 years of age with IMD were retrospectively identified from the files of the Hellenic National Meningitis Reference Laboratory (HNML) from 2010–2020, and their medical records were tracked from the corresponding hospitals. Demographic, clinical, and microbiological data were recorded for each case. A total of 161 patients younger than 16 years of age admitted to nine hospitals across the country were identified. Of those, 91 (56.5%) records were found. The patients’ median age was 36 months (range 22 days to 16 years old); 37.4% presented with meningitis, 36.2% with both septicemia and meningitis, and 26.4% only with septicemia. The mortality rate was 5.5% and was significantly associated with septicemia, abnormal platelet count at presentation, ICU admission, and coagulation disorders, while sequelae were detected in 16.9% of patients upon discharge. Neisseria meningitidis serogroup B (MenB) was the most predominant (77%); of these, 269 cc was identified (36.8%). This is the first study on unfavorable sequelae and mortality due to IMD performed in Greece. Full article
(This article belongs to the Collection Advances in Public Health Microbiology)
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14 pages, 3026 KiB  
Article
A Bioluminescence-Based Serum Bactericidal Assay to Detect Bactericidal Antibodies Against Neisseria meningitidis in Human Sera
by Giulia Fantoni, Ala-Eddine Deghmane, François Caron and Muhamed-Kheir Taha
Microorganisms 2025, 13(3), 595; https://doi.org/10.3390/microorganisms13030595 - 4 Mar 2025
Viewed by 1103
Abstract
Serum bactericidal assay (SBA) is a functional assay that evaluates infection- and vaccine-induced neutralizing antibodies representing the serological correlate of protection against Neisseria meningitidis. However, it is time consuming due to its readout using the enumeration of colony-forming units (CFUs), making this [...] Read more.
Serum bactericidal assay (SBA) is a functional assay that evaluates infection- and vaccine-induced neutralizing antibodies representing the serological correlate of protection against Neisseria meningitidis. However, it is time consuming due to its readout using the enumeration of colony-forming units (CFUs), making this conventional SBA (C-SBA) difficult for large-scale use. We developed a new SBA method that takes advantage of a bioluminescence N. meningitidis serogroup B (BioLux-SBA). The assay development steps involved the human complement source validation, the setup of the optimal incubation time, and the assessment of intra-day and inter-day variability. BioLux-SBA was then compared to C-SBA using a serum collection of Norman children vaccinated in 2011 with MenBvac, an OMV meningococcal vaccine. While a conventional approach requests 48 h of work to test 24 sera per day, BioLux-SBA takes only 5 h to test 96 sera per day. The SBA titers (n = 10) correlated with R2 of 0.98 (p-value < 0.0001). The deposition of terminal complement components (C5b-C9) measured by flow cytometry on the bacterial surface well correlated with BioLux SBA titers. This high-throughput method to evaluate the immunogenicity of meningococcal vaccines appears to be a reliable method for an OMV meningococcal B vaccine and requires further assessment in other laboratories and against other meningococcal vaccines. Full article
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18 pages, 5736 KiB  
Article
Surveillance of Pediatric Invasive Bacterial Diseases in the Veneto Region: Epidemiological Trends and Outcomes over 17 Years (2007–2023)
by Silvia Cocchio, Claudia Cozzolino, Andrea Cozza, Patrizia Furlan, Enrica Frasson, Sara Tarantino, Elisabetta Conte, Lorenzo Chiusaroli, Irene Amoruso, Francesca Zanella, Davide Gentili, Michele Tonon, Francesca Russo, Tatjana Baldovin and Vincenzo Baldo
Vaccines 2025, 13(3), 230; https://doi.org/10.3390/vaccines13030230 - 24 Feb 2025
Viewed by 823
Abstract
Introduction: Invasive bacterial diseases (IBDs) such as meningitis and sepsis are significant public health concerns, particularly in pediatric populations. This study analyzes the incidence, outcomes, and bacterial serotype distribution of pediatric IBDs in the Veneto Region over 17 years. Methods: An observational study [...] Read more.
Introduction: Invasive bacterial diseases (IBDs) such as meningitis and sepsis are significant public health concerns, particularly in pediatric populations. This study analyzes the incidence, outcomes, and bacterial serotype distribution of pediatric IBDs in the Veneto Region over 17 years. Methods: An observational study was conducted using data (2007–2023) from the surveillance system of the Veneto Region, including microbiologically confirmed cases in individuals < 18 years. Differences by age groups and trends were statistically assessed. Results: A total of 535 pediatric IBD cases were reported, with Streptococcus pneumoniae (54.6%), Neisseria meningitidis (19.6%), and Streptococcus agalactiae (13.5%) being the most common pathogens. Haemophilus influenzae infections were more commonly represented in infants under 1 year (41.5%), whereas S. pneumoniae and N. meningitidis were more frequent in the 1–4-year age group (40.8% and 37.1%, respectively). Sepsis was the most common clinical presentation (57.2%), followed by meningitis (36.3%). Serotype analysis revealed that S. pneumoniae serotype 3 was the most prevalent, while serogroup B dominated N. meningitidis cases. Temporal trends generally showed a decline in cases until 2019, a drop during the COVID-19 pandemic, and a subsequent resurgence in 2022–2023. Conclusions: Our research underscores the value of evidence-based epidemiology through robust surveillance systems in tracking IBD trends and serotype shifts, essential for guiding vaccination strategies and public health interventions. These insights highlight the effectiveness of vaccination programs and the necessity of ongoing monitoring to inform public health policies. Improved data integration and completeness are recommended to enhance surveillance accuracy. Full article
(This article belongs to the Special Issue Vaccination and Public Health in the 21st Century)
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10 pages, 561 KiB  
Article
Characterization of Unusual Serogroups of Neisseria meningitidis
by Samy Taha, Giulia Fantoni, Eva Hong, Aude Terrade, Oumar Doucoure, Ala-Eddine Deghmane and Muhamed-Kheir Taha
Microorganisms 2024, 12(12), 2528; https://doi.org/10.3390/microorganisms12122528 - 7 Dec 2024
Cited by 1 | Viewed by 1290
Abstract
Most cases of invasive meningococcal disease (IMD) in Europe are caused by isolates of the Neisseria meningitidis serogroups B, C, W, and Y. We aimed to explore cases caused by other unusual serogroups. We retrospectively screened IMD cases in the databases of the [...] Read more.
Most cases of invasive meningococcal disease (IMD) in Europe are caused by isolates of the Neisseria meningitidis serogroups B, C, W, and Y. We aimed to explore cases caused by other unusual serogroups. We retrospectively screened IMD cases in the databases of the National Reference Center for Meningococci and Haemophilus influnezae in France between 2014 and 2023. Age, sex, serogroups, and genetic lineage distributions were analyzed. We also measured complement deposition on the bacterial surface and tested coverage by vaccines against serogroup B. Cases due to isolates of serogroups other than B, C, W, and Y represented 1.6% of all 3610 IMD cases during the study period with 59 cases and a median age of 21.5 years of age. The corresponding isolates were non-groupable (26 cases), serogroup X (21 cases), serogroup E (11 cases), and one isolate belonged to serogroup Z. Only a low proportion (7.4%) belonged to the hyperinvasive genetic lineages. Isolates of serogroup E bound a significantly higher amount of complement on their surface and were mainly detected in patients with terminal complement pathway deficiencies. Isolates of these unusual serogroups were shown to be covered by vaccines licensed against meningococci B. Surveillance of these isolates needs to be enhanced. Full article
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17 pages, 1815 KiB  
Article
Protective Antimicrobial Effect of the Potential Vaccine Created on the Basis of the Structure of the IgA1 Protease from Neisseria meningitidis
by Yuri Prokopenko, Alexei Zinchenko, David Karlinsky, Olga Kotelnikova, Olga Razgulyaeva, Elena Gordeeva, Elena Nokel, Oxana Serova, Elena Kaliberda, Larisa Zhigis, Lev Rumsh and Ivan Smirnov
Vaccines 2024, 12(12), 1355; https://doi.org/10.3390/vaccines12121355 - 30 Nov 2024
Viewed by 1331
Abstract
Background/Objectives: IgA1 protease is one of the virulence factors of Neisseria meningitidis, Haemophilus influenzae and other pathogens causing bacterial meningitis. The aim of this research is to create recombinant proteins based on fragments of the mature IgA1 protease A28–P1004 [...] Read more.
Background/Objectives: IgA1 protease is one of the virulence factors of Neisseria meningitidis, Haemophilus influenzae and other pathogens causing bacterial meningitis. The aim of this research is to create recombinant proteins based on fragments of the mature IgA1 protease A28–P1004 from N. meningitidis serogroup B strain H44/76. These proteins are potential components of an antimeningococcal vaccine for protection against infections caused by pathogenic strains of N. meningitidis and other bacteria producing serine-type IgA1 proteases. Methods: To obtain promising antigens for creating a vaccine, we designed and obtained several recombinant proteins. These proteins consisted of single or directly connected fragments selected from various regions of the IgA1 protease A28–P1004. The choice of these fragments was based on our calculated data on the distribution of linear and conformational B-cell epitopes and MHC-II T-cell epitopes in the structure of IgA1 protease, taking into account the physicochemical properties of potential compounds and the results of a comparative analysis of the spatial structures of the original IgA1 protease and potential recombinant proteins. We studied the immunogenic and protective effects of the obtained proteins on the BALB/c mice against meningococci of serogroups A, B and C. Results: Proteins MA28–P1004-LEH6, MW140–K833-LEH6, MW329–P1004-LEH6, M(W140–H328)-(W412–D604)-(Y866–P1004)-LEH6 and M(W140–Q299)-(Y866–P1004)-LEH6 have shown the following antibody titers, 103/titer: 11 ± 1, 6 ± 2, 6 ± 1, 9 ± 1 and 22 ± 3, respectively. Also, the last two proteins have shown the best average degree of protection from N. meningitidis serogroups A, B and C, %: 62 ± 6, 63 ± 5, 67 ± 4 respectively for M(W140–H328)-(W412–D604)-(Y866–P1004)-LEH6 and 70 ± 5, 66 ± 6, 83 ± 3 respectively for M(W140–Q299)-(Y866–P1004)-LEH6. Conclusions: We selected two recombinant proteins consisting of two (M(W140–Q299)-(Y866–P1004)-LEH6) or three (M(W140–H328)-(W412–D604)-(Y866–P1004)-LEH6) linked fragments of IgA1 protease A28–P1004 as candidate active component for an antimeningococcal vaccine. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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13 pages, 2670 KiB  
Article
Immunity Dynamics of Neisseria meningitidis Serogroups ACYW from Birth and Following Vaccination
by Lilian Zeng, Yingyin Deng, Chumin Liang, Zixia Qian, Yueling Chen, Huifang Lin, Runyu Yuan, Pingping Zhou, Xue Zhuang, Ying Yang, Qi Zhu, Limei Sun, Jianfeng He and Jiufeng Sun
Vaccines 2024, 12(11), 1274; https://doi.org/10.3390/vaccines12111274 - 13 Nov 2024
Viewed by 1341
Abstract
Background: Serosurveillance of epidemic cerebrospinal meningitis (ECM) in healthy individuals is crucial for assessing disease risk and evaluating the effectiveness of vaccinations. However, this practical work is rare in China. Methods: We conducted cross-section serosurveillance in Guangzhou, Zhanjiang, and Heyuan in [...] Read more.
Background: Serosurveillance of epidemic cerebrospinal meningitis (ECM) in healthy individuals is crucial for assessing disease risk and evaluating the effectiveness of vaccinations. However, this practical work is rare in China. Methods: We conducted cross-section serosurveillance in Guangzhou, Zhanjiang, and Heyuan in Guangdong Province, measuring Anti-Nm IgG with serogroups A, C, Y, and W, and analyzed the trends using a generalized additive model (GAM). Results: During 2019–2022, 7752 participants were included. The overall antibody positivity rate for serogroups A, C, Y, and W were 60.75%, 15.51%, 32.83%, and 14.56%, respectively. High Anti-Nm IgG was in children aged 0–5 and 5–10 years old. Geometric mean concentrations (GMCs) of Anti-Nm IgG were higher and correlated positively with vaccine doses compared with unvaccinated individuals. The GMC showed a consistent decrease trend in the vaccinated and a U-shaped curve in populations. The declined rates of GMC were 1.59 (95% CI: 1.03, 2.14) µg/mL, 1.65 (95% CI: 1.28, 2.03), 0.62 (95% CI: 0.22, 1.03), and 0.31 (95% CI: 0.08, 0.53) µg/mL per year for serogroups A, C, Y, and W, respectively. Conclusions: There were differences in antibody positivity rate and GMC for the four serogroups of ECM in the healthy individuals of Guangdong Province, with serogroup A showing the highest, and the demographic differences highlighted the high seroprevalence of Neisseria meningitidis in younger people. The variable prevalence rates among serogroups A, C, Y, and W and the observed decline in antibody titers underscore the need for adjustments in the immunization program targeting the meningococcal vaccine. Full article
(This article belongs to the Section Vaccines and Public Health)
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10 pages, 572 KiB  
Article
Meningococcal Carriage in Children with Atypical Hemolytic Uremic Syndrome Receiving Eculizumab Therapy
by Asli Kavaz Tufan, Fatma Ozak Batibay, Gulsah Kaya Aksoy, Bora Gulhan, Beltinge Demircioglu Kilic, Ismail Dursun, Bahar Buyukkaragoz, Aysun Caltik Yilmaz, Hulya Nalcacioglu, Tulay Becerir, Nuran Cetin, Kubra Celegen, Meltem Dinleyici, Mucahit Kaya, Omer Kilic and Ener Cagri Dinleyici
Children 2024, 11(10), 1164; https://doi.org/10.3390/children11101164 - 25 Sep 2024
Viewed by 1460
Abstract
Background/Objectives: Eculizumab is a first-line treatment for atypical hemolytic uremic syndrome (aHUS), and patients undergoing eculizumab therapy may become more susceptible to infection caused by Neisseria meningitidis (Nm). While meningococcal vaccination is required for patients undergoing eculizumab therapy, there is limited [...] Read more.
Background/Objectives: Eculizumab is a first-line treatment for atypical hemolytic uremic syndrome (aHUS), and patients undergoing eculizumab therapy may become more susceptible to infection caused by Neisseria meningitidis (Nm). While meningococcal vaccination is required for patients undergoing eculizumab therapy, there is limited knowledge about meningococcal carriage in children with aHUS. We aimed to evaluate (1) the prevalence of Nm carriage, (2) serogroup distribution, and (3) the immunization status of children undergoing eculizumab treatment for aHUS. Methods: The Meningo-aHUS study is a prospective, multi-center study evaluating meningococcal carriage in children and adolescents in Türkiye receiving eculizumab for aHUS. We noted the age, gender, daycare, school, or university attendance, passive smoking status, previous infection and antibiotic use, and previous immunization history, including meningococcal vaccines, from the medical records of those children with aHUS. We collected nasopharyngeal samples, tested them for Nm using real-time polymerase chain reaction, and performed a serogroup analysis on the positive samples. Results: We collected nasopharyngeal samples from 62 children with aHUS. Out of 62 children, 61 (98.4%) had received at least one dose of the meningococcal vaccine. The median time since the last meningococcal vaccine dose was 15 months (1–59 months). We detected meningococcal carriage in three (4.8%, 95% CI 1.0–13.5) children, and all three strains were non-groupable (NG). No other serogroups were detected. Conclusions: Almost all the children received their risk-group meningococcal immunization, including booster doses. A 4.8% of children with aHUS carried NG meningococci and, no vaccine serogroups were detected. Patients treated with eculizumab remain profoundly susceptible to IMD due to these NG meningococcal strains. The occurrence of breakthrough cases and carriage of Nm, especially NG strains, highlights the significance of maintaining a state of constant alertness, promptly seeking medical attention, and swiftly treating any symptoms that align with IMD, regardless of their vaccination status or antibiotic prophylaxis. Full article
(This article belongs to the Section Pediatric Nephrology & Urology)
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8 pages, 809 KiB  
Brief Report
Enhanced Timeliness and Co-Administration of Meningitis B Vaccination in Children: Impact of Funding in Valencian Community, Spain
by Juan Juaneda, Pablo Estrella-Porter, Carolina Blanco-Calvo, Alejandro Orrico-Sánchez, José Antonio Lluch-Rodrigo and Eliseo Pastor-Villalba
Vaccines 2024, 12(6), 623; https://doi.org/10.3390/vaccines12060623 - 5 Jun 2024
Cited by 1 | Viewed by 1719
Abstract
Public funding of vaccines may enhance vaccination rates, co-administration, and timeliness. The impacts of including the serogroup B meningococcus vaccine (MenB) into the national immunisation schedule on vaccination rates, co-administration rates, and timeliness were assessed using a population-based pre-funding (2022) and post-funding (2023) [...] Read more.
Public funding of vaccines may enhance vaccination rates, co-administration, and timeliness. The impacts of including the serogroup B meningococcus vaccine (MenB) into the national immunisation schedule on vaccination rates, co-administration rates, and timeliness were assessed using a population-based pre-funding (2022) and post-funding (2023) study design. MenB vaccination rates improved after funding and were in line with previously funded vaccines. Co-administration rates also increased significantly. Timely administration increased, protecting children at an early age. Public funding has a positive impact on vaccine accessibility and early protection. Consistent population characteristics highlight the role of funding. Full article
(This article belongs to the Special Issue Vaccines and Vaccinations in the Pandemic Period)
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13 pages, 1050 KiB  
Article
Extensive Genetic Diversity and Epidemiological Patterns of Factor H-Binding Protein Variants among Neisseria meningitidis in China
by Zhizhou Tan, Juan Xu, Jie Che, Li Xu, Dongshan Yan, Maojun Zhang and Zhujun Shao
Microorganisms 2024, 12(3), 481; https://doi.org/10.3390/microorganisms12030481 - 27 Feb 2024
Viewed by 1949
Abstract
Factor H-binding protein (fHbp) is a virulence factor expressed by Neisseria meningitidis (N. meningitidis), the primary causative agent of invasive meningococcal disease (IMD) in humans. fHbp is utilized as the main component in vaccines to provide protection against IMD caused by [...] Read more.
Factor H-binding protein (fHbp) is a virulence factor expressed by Neisseria meningitidis (N. meningitidis), the primary causative agent of invasive meningococcal disease (IMD) in humans. fHbp is utilized as the main component in vaccines to provide protection against IMD caused by serogroup B N. meningitidis. In order to comprehensively investigate the genetic diversity and epidemiological patterns of fHbp variants within isolates of Chinese N. meningitidis, we utilized the NEIS0349 locus, which encompasses the complete coding sequences of fHbp. This enabled us to identify allelic variants of fHbp with enhanced resolution. A total of 109 fHbp variants were identified in 1013 Chinese N. meningitidis isolates. We reconstructed a phylogenetic tree and analyzed the epidemiological characteristics of each variant. Considering both temporal and geographical distribution patterns, only four fHbp variants (v2.16, v2.18, v2.404, and v2.21) exhibited persistent nationwide prevalence during the previous decade (2011–2021). These variants were highly prevalent in both serogroup B strains from patients and healthy individuals, suggesting their potential as suitable vaccine candidates for nationwide implementation against IMD caused by serogroup B strains. Our study emphasizes the significance of conducting continuous surveillance of meningococcal strains to monitor the genetic diversity of fHbp for the purpose of vaccine development. Full article
(This article belongs to the Section Medical Microbiology)
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