Search Results (31)

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 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

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

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

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

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

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

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

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

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

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

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

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

Neisseria meningitidis (N. meningitidis) serogroup B (MenB) is the leading cause of invasive meningococcal disease worldwide. The pathogen has a wide range of virulence factors, which are potential vaccine components. Studying the genetic variability of antigens within a population, especially their long-term persistence, is necessary to develop new vaccines and predict the effectiveness of existing ones. The multicomponent 4CMenB vaccine (Bexsero), used since 2014, contains three major genome-derived recombinant proteins: factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisserial adhesin A (NadA). Here, we assessed the prevalence and sequence variations of these vaccine antigens in a panel of 5667 meningococcal isolates collected worldwide over the past 10 years and deposited in the PubMLST database. Using multiple amino acid sequence alignments and Random Forest Classifier machine learning methods, we estimated the potential strain coverage of fHbp and NHBA vaccine variants (51 and about 25%, respectively); the NadA antigen sequence was found in only 18% of MenB genomes analyzed, but cross-reactive variants were present in less than 1% of isolates. Based on our findings, we proposed various strategies to improve the 4CMenB vaccine and broaden the coverage of N. meningitidis strains. Full article

Invasive meningococcal disease (IMD) is a devastating disease with significant mortality and long-term morbidity. The COVID-19 pandemic and containment measures have affected the epidemiology of infectious pathogens. This study’s aim was to assess IMD trends in Israel prior to and during the COVID-19 pandemic. The Neisseria meningitidis invasive infection is a notifiable disease in Israel. Laboratory analysis includes serogrouping and molecular characterization. The overall national IMD incidence rate (1998–2022) was 0.8/100,000 population. The IMD incidence rates declined during the pandemic years (0.3/100,000 in 2020–2022 vs. 0.9/100,000 in 1998–2019). The number of notified IMD cases declined by 65% in 2020–2022. The case fatality rate among laboratory-confirmed IMD cases was 9% (47/521, 2007–2022). Mortality risk markers included cases’ age (older) and socio-economic status (lower). Overall, most Neisseria meningitidis isolates were of serogroup B (62.6%), and the most prevalent clonal complex (CC) was CC32 (24.2%). Serogroup B prevailed in cases aged 0–9 years (74.5%) and less in cases aged 10 years and above (39%). Neisseria meningitidis serogroups and CC distribution altered recently with a decline in serogroup B fraction, an increase in serogroup Y, and a decline in CC32. Ongoing IMD surveillance is necessary to assess trends in circulating strains and support decision-making on meningococcal vaccination programs. Full article