Meningitidis Serogroup Research Articles

Bioinformatics Analysis of Global Diversity in Meningococcal Vaccine Antigens over the Past 10 Years: Vaccine Efficacy Prognosis.

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.

Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines.

Glycoconjugate vaccines play a major role in the prevention of infectious diseases worldwide, with significant impact on global health, enabling the polysaccharides to induce immunogenicity in infants and immunological memory. Tetanus toxoid (TT), a chemically detoxified bacterial toxin, is among the few carrier proteins used in licensed glycoconjugate vaccines. The recombinant full-length 8MTT was engineered in E. coli with eight individual amino acid mutations to inactivate three toxin functions. Previous studies in mice showed that 8MTT elicits a strong IgG response, confers protection, and can be used as a carrier protein. Here, we compared 8MTT to traditional carrier proteins TT and cross-reactive material 197 (CRM197), using different polysaccharides as models: Group A Streptococcus cell-wall carbohydrate (GAC), Salmonella Typhi Vi, and Neisseria meningitidis serogroups A, C, W, and Y. The persistency of the antibodies induced, the ability of the glycoconjugates to elicit booster response after re-injection at a later time point, the eventual carrier-induced epitopic suppression, and immune interference in multicomponent formulations were also evaluated. Overall, immunogenicity responses obtained with 8MTT glycoconjugates were compared to those obtained with corresponding TT and, in some cases, were higher than those induced by CRM197 glycoconjugates. Our results support the use of 8MTT as a good alternative carrier protein for glycoconjugate vaccines, with advantages in terms of manufacturability compared to TT.

Epidemic forecast and preparedness for explosive-cerebrospinal meningitis outbreak in Nigeria using the preventive vaccination strategy.

Within the African meningitis belt, yearly outbreaks of cerebrospinal meningitis (CSM), with incidence rates of 10-100 cases per 100 000 population, are typically punctuated by explosive epidemics occurring every 8-12 years, with incidence rates that can exceed 1000 cases per 100 000 population. From 1928 to 2018, Nigeria recorded the highest number (21%) of cases in the region. The reactive vaccination strategy, a protocol with major drawbacks, has been the vaccination method utilised in Nigeria. This review highlights the need for governments within the African meningitis belt to start preparations against the next explosive CSM epidemic expected to occur between 2024 and 2028 using the preventive vaccination strategy. We performed a literature search on the Google Scholar search engine using relevant search strings and included studies and reports between 1905 and 2022 that met set criteria. Neisseria meningitidis serogroups A, B, C, W135, X, and Y; Haemophilus influenzae serotypes a, b, c, e, and f; and Streptococcus pneumoniae serotypes 1, 4, 5, 6, 9, 19, 19F, and 20 were implicated as aetiologies. However, the reactive vaccination strategy was only used against N. meningitidis A or C, H. influenzae b, and pneumococcal conjugate vaccine. Between 2011 and 2017, a polysaccharide vaccine (ACW or ACYW) active against serogroups A, C, W and Y was used within the African meningitis belt for the first time. Varying genotypes of N. meningitidis, H. influenzae and S. pneumoniae were identified. Our results revealed a very high success rate for the preventive vaccination strategy. In order to ensure reductions in the morbidity and mortality associated with invasive CSM, the Federal Ministry of Health, Nigeria, should leverage existing knowledge of the circulating serogroups, serotypes, and genotypes of the primary bacterial aetiologies and commence the implementation of the preventive vaccination strategy.

Meningococcal Surveillance Australia - Reporting period 1 January to 31 March 2023.

The reference laboratories of the National Neisseria Network, Australia report data on invasive meningococcal disease (IMD) cases confirmed by culture and/or molecular techniques for the Australian Meningococcal Surveillance Programme (AMSP). Culture-positive cases and molecular-based diagnoses are defined as IMD by the Communicable Diseases Network Australia National Guidelines for Public Health Units.1 Data contained in the quarterly reports are restricted to a description of the number of cases by jurisdiction and serogroup, when known. Some minor corrections to data in Table 1 may be made in subsequent reports if additional data are received. IMD notifications in Australia in the first quarter of 2023 were greater than in the corresponding period in 2022 but still below the 36 IMD cases reported in quarter one of 2019 (prior to the SARS-CoV-2 pandemic).2 Notably, the predominance of N. meningitidis serogroup B (MenB) IMD continued in the first quarter of 2023 (21/23, 91.3% of notifications), showing an increase from 84% in the fourth quarter of 2022.3 In contrast, between 2019 and 2021, 50–62% of IMD was attributable to MenB.4 A full analysis of laboratory-confirmed cases of IMD in each calendar year is contained in the AMSP annual report published in Communicable Diseases Intelligence.

Vaccine-preventable Pediatric Acute Bacterial Meningitis in France: A Time Series Analysis of a 19-Year Prospective National Surveillance Network.

In France, vaccination has been implemented against Hi serotype b (Hib), pneumococcus with pneumococcal conjugate vaccines (PCV), and Neisseria meningitidis serogroup C (MenC). These interventions with different coverage and uptake have disrupted the epidemiology of vaccine-preventable acute bacterial meningitis (ABM). We analyzed data from a French prospective surveillance network of ABM in children ≤15 years old enrolled by 259 pediatric wards (estimated national coverage: 61%). From 2001 to 2020, the effect of vaccine implementation was estimated with segmented linear regression. We analyzed 7,186 cases, mainly due to meningococcus (35.0%), pneumococcus (29.8%), and Hi (3.7%). MenC ABM incidence decreased (-0.12%/month, 95% CI: -0.17 to -0.07, P < 0.001) with no change for the overall meningococcal ABM when comparing the pre-MenC vaccination and the post-MenC vaccination trends. Despite a decreasing MenB ABM incidence without a vaccination program (-0.43%/month, 95% CI: -0.53 to -0.34, P < 0.001), 68.3% of meningococcal ABM involved MenB. No change in pneumococcal ABM incidence was observed after the PCV7 recommendation. By contrast, this incidence significantly decreased after the switch to PCV13 (-0.9%/month, 95% CI: -1.6 to -0.2%, P = 0.01). After May 2014, a rebound occurred (0.5%/month, 95% CI: 0.3-0.8%, P < 0.001), with 89.5% of non-PCV13 vaccine serotypes. Hib ABM incidence increased after June 2017. PCV7 and MenC vaccine introduction in France, with slow vaccine uptake and low coverage, had no to little impact as compared to the switch from PCV7 to PCV13, which occurred when coverage was optimal. Our data suggest that MenB and next-generation PCVs could prevent a large part of the ABM incidence in France.

Structured Benefit-Risk Assessment of a New Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) in Individuals Ages 12 Months and Older.

A favorable benefit-risk balance is required to support licensure of biologics, in keeping with regulatory agencies' evolving recommendations, including the United States Food and Drugs Administration. We present a structured semi-quantitative benefit-risk analysis of MenACYW-TT, a quadrivalent meningococcal conjugate vaccine against Neisseria meningitidis serogroups, A, C, W and Y versus licensed comparators in individuals aged ≥ 12 months. We used data from six MenACYW-TT clinical trials, stratified by age group, versus licensed vaccines: toddlers (12-23 months; Nimenrix® [MCV4-TT]), children (2-9 years; Menveo® [MCV4-CRM]), adolescents (10-17 years; MCV4-CRM or Menactra® [MCV4-DT]), adults (18-55 years; MCV4-DT) and older adults (≥ 56 years; Menomune®-A/C/Y/W-135 [MPSV4]). Eight benefit (seroresponse and seroprotection for A, C, W and Y) and five risk outcomes (any and grade 3 solicited injection site and systemic reactions, and serious adverse events) were measured at Day 30 after initial vaccination. Analyses were conducted by baseline vaccination status (meningococcal vaccine-naïve or vaccine-primed). MenACYW-TT showed favorable seroresponse and seroprotection among vaccine-naïve participants aged ≥ 2years, against all serogroups, compared with MCV4-CRM, MCV4-DT and MPSV4. In vaccine-naïve toddlers, there was a favorable effect for serogroup C, but no difference between MenACYW-TT and MCV4-TT for serogroups A, Y and W. A favorable effect for MenACYW-TT against serogroup C was observed in all vaccine-naïve and combined vaccine-naïve and MenC conjugate vaccine-primed groups. For all risk criteria, there were no differences between MenACYW-TT and MCV4s in toddlers, children, adolescents and adults. Results for solicited injection site and systemic reactions favored MPSV4 in older adults. The benefit-risk profile for MenACYW-TT showed favorable seroresponse and seroprotection in individuals aged ≥ 2 years and no difference in risk criteria between MenACYW-TT and MCV4s. MenACYW-TT may provide an alternative to the standard-of-care for meningococcal disease prevention in those aged ≥ 12 months.

Promising pharmaceutical development of vaccines for the prevention of meningococcal infection

Meningococcal infection (MI) refers to anthroponoses; is an acute infectious disease with an aerosol transmission mechanism, characterized by various forms of the infectious process: from local (nasopharyngitis) and asymptomatic infections to generalized forms of invasive infection with the development of meningococcemia and meningitis. The causative agent of MI is meningococcus (Neisseria meningitidis) that belongs to the pathogen risk group 2. Preventive vaccination against MI is included in the calendar of preventive vaccinations according to epidemic indications. The problem of MI retains a great medical and social significance for Russian health care due to the continuing high rates of associated mortality, disability, high costs of treatment and rehabilitation. Vaccines against five of the six main N. meningitidis serogroups have been registered worldwide. Serogroup X vaccine is under development. Recently, there has been an increase in the heterogeneity of the meningococcal population due to serogroups W, Y, and X. The polysaccharide vaccines developed in Russia have restrictions on their use, and there is no full-cycle production of meningococcal conjugate vaccines in the Russian Federation. Given the above, the development and registration of new vaccines against MI is an urgent task.&#x0D; The purpose of this work is to analyze the current state of development of vaccines for MI prevention. Currently, depending on the production technology, the following types of meningococcal vaccines are available: polysaccharide, conjugated, based on outer membrane vesicles (OMV), protein and based on synthetic polysaccharides. Serogroup-targeted meningococcal vaccines are effective in reducing the public health burden of invasive MI. Polysaccharide conjugate and protein/OMV vaccines are among the most promising vaccines for most invasive meningococcal serogroups. In modern conditions, with the progress in technologies for future polysaccharide conjugate vaccines, new opportunities are opening up for the use of such approaches as chemical/enzymatic synthesis, improved characteristics of the carrier protein, and site-specific conjugation. The development of a single vaccine against the main invasive meningococcal serogroups, rather than its individual antigenic variants, does not lose its relevance. It is timely to develop in the near future a vaccine against N. meningitidis serogroup X, which was previously a rare cause of sporadic meningitis, but has caused outbreaks in various African countries in 20062010 and in recent years.

Invasive Disease Due to Neisseria meningitidis: Surveillance and Trends in Israel Prior to and during the COVID-19 Pandemic.

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.

Accuracy of antigen tests for meningococcal meningitis in cerebrospinal fluid: A diagnostic meta-analysis.

Neisseria meningitidis is one of the major pathogens of meningitis in children worldwide and causes invasive meningococcal disease (IMD), which is a critical illness that mainly presents as meningitis and/or septicemia in children. Identification of N. meningitidis in cerebrospinal fluid (CSF) is the gold standard for the diagnosis of meningococcal meningitis, but antigen tests have advantages such as timely results, relatively low cost, and convenience. Yet, the diagnostic accuracy of antigen tests remains uncertain. Therefore, the aim of this meta-analysis was to evaluate the diagnostic accuracy of antigen tests for N. meningitidis in CSF. We searched the PubMed, Embase, and Cochrane Library databases for studies evaluating the diagnostic accuracy of antigen tests for N. meningitidis in CSF. We included studies that provided sufficient data to construct a 2 × 2 table on a per-sample basis. To determine the overall sensitivity and specificity of the antigen tests, we used polymerase chain reaction (PCR) as the reference standard and employed the hierarchical summary receiver operating characteristic model. Nine studies with 4533 CSF samples were included. The meta-analysis yielded a pooled sensitivity of 91.2% (95% confidence interval [CI]: 80.0%-100.0%) and a pooled specificity of 93.8% (95% CI: 83.9%-100.0%). A subgroup analysis of 2 studies that reported the outcomes of MeningoSpeed yielded a pooled sensitivity of 93.4% (95% CI: 90.0%-95.8%) and a pooled specificity of 91.9% (95% CI: 88.6%-94.4%). Antigen testing for the N. meningitidis serogroup X had a pooled sensitivity of 92.4% (95% CI: 85.2%-96.2%) and a pooled specificity of 99.2% (95% CI: 78.7%-100.0%). The studied antigen tests had high sensitivity and specificity for the diagnosis of meningococcal meningitis in CSF specimens. Antigen testing could serve as an accurate diagnostic method for assessing patients who have a suspected N. meningitidis infection.

Antibodies against Neisseria meningitidis serogroups A, C, W and Y in serum and saliva of Norwegian adolescents

IntroductionThe incidence of invasive meningococcal disease (IMD) among Norwegian 16–19-year-olds was 1–7/100,000 in the decade before the COVID-19 pandemic, with serogroup Y (MenY) dominance. In contrast to many other European countries, meningococcal vaccines are not part of the national immunisation program (NIP) in Norway. This cross-sectional study aimed to measure the degree of natural immunity against Neisseria meningitidis among adolescents in Norway to evaluate the need for introducing tetravalent meningococcal conjugate vaccine (MCV4) in the NIP. Materials and methodsSerum and saliva samples were collected from students in upper and lower secondary schools in Norway in 2018. Samples were analysed for meningococcal capsular polysaccharide (PS)-specific antibodies using a bead-based multiplex immunoassay. PS-specific antibody levels were linked to data on meningococcal carriage, vaccination status and risk factors for carriage (assessed with questionnaire) and analysed by linear regression of log transformed concentrations. A subset of samples from unvaccinated individuals was analysed for serum bactericidal antibodies (SBA). ResultsA total of 1344 participants, median age 16 years (range 12–24), were included in the study. Overall, 60.9% of the participants were female and 1137 (84.6%) were not vaccinated with MCV4. PS-specific antibody concentrations in serum and saliva were low among unvaccinated individuals for all serogroups and only 6.7–20.0% of the subpopulation with high PS-specific antibodies assessed with SBA had protective levels. Unvaccinated MenY carriers had higher levels of MenY anti-PS IgG in serum and IgA in saliva than those not carrying MenY. Use of Swedish snus was associated with lower anti-PS IgG levels in serum and waterpipe use with lower anti-PS IgG levels in saliva. ConclusionUnvaccinated adolescents in Norway have a low degree of natural immunity against the serogroups of N. meningitidis predominating among cases of IMD in this age group. Therefore, introduction of MCV4 for adolescents in the NIP is recommended.

Immune responses to Neisseria gonorrhoeae and implications for vaccine development.

Neisseria gonorrheoae is the causative agent of gonorrhea, a sexually transmitted infection responsible for a major burden of disease with a high global prevalence. Protective immunity to infection is often not observed in humans, possible due to high variability of key antigens, induction of blocking antibodies, or a large number of infections being relatively superficial and not inducing a strong immune response. N. gonorrhoeae is a strictly human pathogen, however, studies using mouse models provide useful insights into the immune response to gonorrhea. In mice, N. gonorrhoea appears to avoid a protective Th1 response by inducing a less protective Th17 response. In mouse models, candidate vaccines which provoke a Th1 response can accelerate the clearance of gonococcus from the mouse female genital tract. Human studies indicate that natural infection often induces a limited immune response, with modest antibody responses, which may correlate with the clinical severity of gonococcal disease. Studies of cytokine responses to gonococcal infection in humans provide conflicting evidence as to whether infection induces an IL-17 response. However, there is evidence for limited induction of protective immunity from a study of female sex workers in Kenya. A controlled human infection model (CHIM) has been used to examine the immune response to gonococcal infection in male volunteers, but has not to date demonstrated protection against re-infection. Correlates of protection for gonorrhea are lacking, which has hampered the progress towards developing a successful vaccine. However, the finding that the Neisseria meningitidis serogroup B vaccines, elicit cross-protection against gonorrhea has invigorated the gonococcal vaccine field. More studies of infection in humans, either natural infection or CHIM studies, are needed to understand better gonococcal protective immunity.

Stability of lyophilized Meningococcal A conjugate vaccine, (MenAfriVac™) at elevated temperatures to support controlled temperature chain (CTC) claim

Meningococcal A Conjugate Vaccine (MenAfriVac) is the world’s first Monovalent Conjugate Vaccine against Neisseria Meningitidis serogroup A which has obtained Controlled Temperature Chain (CTC) label claim of “stable upto 40°C for 4 days prior to reconstitution” developed by Serum Institute of India Pvt. Ltd. Pune, India and the vaccine was granted permission from World health Organization. This paper elucidates and talks about the layout of various studies performed to characterize the product to declare as CTC at the time when the knowledge and mechanism to describe CTC was not fully known which in term helped to design the CTC guidelines.Product stability was assessed using clinical, consistency and regular lots released by NRA. The critical stability indicating parameters like free polysaccharide, molecular size distribution along with Potency and safety tests were carried out to support the product stability making sure it also qualifies for Vaccine Vial Monitor label claim of VVM30. An additional in use stability (reconstitution) was also performed. All studies indicated that the product remains stable at real time as well as elevated temperatures and well within the specifications approved by NRA and formed the strong basis for CTC claim which is now recommended by WHO.

Computer Aided Reverse Vaccinology: A Game-changer Approach for Vaccine Development.

One of the most dynamic approaches in biotechnology is reverse vaccinology, which plays a huge role in today's developing vaccines. It has the capability of exploring and identifying the most potent vaccine candidate in a limited period of time. The first successful novel approach of reverse vaccinology was observed in Neisseria meningitidis serogroup B, which has revolutionised the whole field of computational biology. In this review, we have summarized the application of reverse vaccinology for different infectious diseases, discussed epitope prediction and various available bioinformatic tools, and explored the advantages, limitations and necessary elements of this approach. Some of the modifications in the reverse vaccinology approach, like pan-genome and comparative reverse vaccinology, are also outlined. Vaccines for illnesses like AIDS and hepatitis C have not yet been developed. Computer Aided Reverse vaccinology has the potential to be a game-changer in this area. The use of computational tools, pipelines and advanced soft-computing methods, such as artificial intelligence and deep learning, and exploitation of available omics data in integration have paved the way for speedy and effective vaccine designing. Is reverse vaccinology a viable option for developing vaccines against such infections, or is it a myth? Vaccine development gained momentum after the spread of various infections, resulting in numerous deaths; these vaccines are developed using the traditional technique, which includes inactivated microorganisms. As a result, reverse vaccinology may be a far superior technique for creating an effective vaccine.

Comparative Transcriptome Profiling of mRNA and lncRNA of Mouse Spleens Inoculated with the Group ACYW135 Meningococcal Polysaccharide Vaccine.

The Group ACYW135 meningococcal polysaccharide vaccine (MPV-ACYW135) is a classical common vaccine used to prevent Neisseria meningitidis serogroups A, C, Y, and W135, but studies on the vaccine at the transcriptional level are still limited. In the present study, mRNAs and lncRNAs related to immunity were screened from the spleens of mice inoculated with MPV-ACYW135 and compared with the control group to identify differentially expressed mRNAs and lncRNAs in the immune response. The result revealed 34375 lncRNAs and 41321 mRNAs, including 405 differentially expressed (DE) lncRNAs and 52 DE mRNAs between the MPV group and the control group. Results of GO and KEGG enrichment analysis turned out that the main pathways related to the immunity of target genes of those DE mRNAs and DE lncRNAs were largely associated with positive regulation of T cell activation, CD8-positive immunoglobulin production in mucosal tissue, alpha-beta T cell proliferation, negative regulation of CD4-positive, and negative regulation of interleukin-17 production, suggesting that the antigens of MPV-ACYW135 capsular polysaccharide might activate T cell related immune reaction in the vaccine inoculation. In addition, it was noted that Bach2 (BTB and CNC homolog 2), the target gene of lncRNA MSTRG.17645, was involved in the regulation of immune response in MPV-ACYW135 vaccination. This study provided a preliminary catalog of both mRNAs and lncRNAs associated with the proliferation and differentiation of body immune cells, which was worthy of further research to enhance the understanding of the biological immune process regulated by MPV-ACYW135.

High-Frequency Changes in Pilin Glycosylation Patterns during Neisseria meningitidis Serogroup a Meningitis Outbreaks in the African Meningitis Belt.

In the meningitis belt of sub-Saharan Africa, there are cyclic meningococcal epidemics that coincide with clonal waves of Neisseria meningitidis carriage and invasive disease. In the framework of longitudinal colonization and disease studies in Ghana and Burkina Faso, meningococcal isolates belonging to the closely related hypervirulent A:ST-5, A:ST-7, and A:ST-2859 clones have been collected from 1998 to 2011 during meningococcal outbreaks. A comparative whole-genome sequencing study with 100 of these isolates identified the pilin glycosylation (pgl) locus as one hot spot of recombination. Frequent exchange of pgl genes in N. meningitidis by lateral gene transfer results in differences in the glycosylation patterns of pilin and other cell surface glycoproteins. In this study, we looked at both recombination and phase variation of the pgl genes of these clinical isolates and analyzed the glycan structures resulting from different pgl alleles and their variable expression. Our results indicate that the basal O-linked sugar of the glycans expressed by these isolates is masked by various additional mono- or disaccharide structures whose expression is highly variable due to the phase-variable expression of pgl genes. We also observed a distinct glycoform in two isolates with pgl loci that were modified by recombination. These data suggest that variation in N. meningitidis protein glycosylation could be crucial for bacterial adaptation to evade herd immunity in semi-immune populations. Investigating pilin glycosylation in N. meningitidis can shed light on the mechanisms by which this pathogen evades the host immune response, and may help identify potential targets for novel therapies and vaccines.

Meningococcal B Immunisation in Adults and Potential Broader Immunisation Strategies: A Narrative Review.

Recombinant vaccines against invasive meningococcal disease due to Neisseria meningitidis serogroup B (MenB) have shown substantial impact in reducing MenB disease in targeted populations. 4CMenB targets four key N. meningitidis protein antigens; human factor H binding protein (fHbp), Neisserial heparin binding antigen (NHBA), Neisseria adhesin A (NadA) and the porin A protein (PorA P1.4), with one or more of these expressed by most pathogenic MenB strains, while MenB-FHbp targets two distinct fHbp variants. While many countries recommend MenB immunisation in adults considered at high risk due to underlying medical conditions or immunosuppression, there are no recommendations for routine use in the general adult population. We reviewed the burden of MenB in adults, where, while incidence rates remain low (and far lower than in young children<5years of age at greatest risk), a substantial proportion of MenB cases (20% or more) is now observed in the adult population; evident in Europe, Australia, and in the United States. We also reviewed immunogenicity data in adults from clinical studies conducted during MenB vaccine development and subsequent post-licensure studies. A 2-dose schedule of 4CMenB generates hSBA titres≥1:4 towards all four key vaccine target antigens in up to 98-100% of subjects. For MenB-FHbp, a≥fourfold rise in hSBA titres against the four primary representative test strains was observed in 70-95% of recipients following a 3-dose schedule. While this suggests potential benefits for MenB immunisation if used in adult populations, data are limited (especially for adults>50years) and key aspects relating to duration of protection remain unclear. Although a broader adult MenB immunisation policy could provide greater protection of the adult population, additional data are required to support policy decision-making.

The meningitis outbreak returns to Niger: Concern, efforts, challenges, and recommendations.

Meningitis, a disease that commonly manifests in African meningitis belt, continues to be a public health problem as it is a fatal disease that leave survivors with long-term effects. Most cases of meningitis are due to bacterial and viral infection, although parasites, fungus, cancer, drugs, and immune disorders can rarely cause meningitis. Stiff neck, high temperature, light sensitivity, disorientation, headaches, and vomiting are the most typical symptoms of meningitis. Niger, being in African meningitis belt, has been affected by many meningitis outbreaks. Since 2015, a total of 20,789 cases and 1369 fatalities (CFR 6.6%) have been documented in Niger. In contrast to earlier seasons, the current outbreak of meningitis in Niger exhibits both an increase in the number of cases and a rise in the growth rate. A total of 559 cases of meningitis, including 18 fatalities (overall CFR 3.2%), were reported in the Zinder Region, southeast of Niger, from 1 November 2022 to 27 January 2023, compared to 231 cases reported from 1 November 2021 to 31 January 2022. In the current outbreak, the Neisseria meningitidis serogroup C (NmC) is responsible for the majority of laboratory confirmed cases (104/111; 93.7%). To organize the response to the outbreak, a global team of WHO and other partners, including MSF and UNICEF, has been sent to Niger. Even though there are many challenges in battle against meningitis in Niger, immunization, antibiotics administration and strong disease surveillance are recommended techniques to cope with the current meningitis outbreak in Niger.

Biochemical and structural characterization of meningococcal methylenetetrahydrofolate reductase.

Methylenetetrahydrofolate reductase (MTHFR) is a key metabolic enzyme in colonization and virulence of Neisseria meningitidis, a causative agent of meningococcal diseases. Here, the biochemical and structural properties of MTHFR from a virulent strain of N. meningitidis serogroup B (NmMTHFR) were characterized. Unlike other orthologs, NmMTHFR functions as a unique homohexamer, composed of three homo-dimerization partners, as shown in our 2.7 Å resolution crystal structure. Six active sites were formed solely within monomers and located away from the oligomerization interfaces. Flavin adenine dinucleotide cofactor formed hydrogen bonds with conserved sidechains, positioning its isoalloxazine ring adjacent to the overlapping binding sites of nicotinamide adenine dinucleotide (NADH) coenzyme and CH2 -H4 folate substrate. NmMTHFR utilized NADH (Km = 44 μM) as an electron donor in the NAD(P)H-CH2 -H4 folate oxidoreductase assay, but not nicotinamide adenine dinucleotide phosphate (NADPH) which is the donor required in human MTHFR. In silico analysis and mutagenesis studies highlighted the significant difference in orientation of helix α7A (Phe215-Thr225) with that in the human enzyme. The extended sidechain of Met221 on helix α7A plays a role in stabilizing the folded structure of NADH in the hydrophobic box. This supports the NADH specificity by restricting the phosphate group of NADPH that causes steric clashes with Glu26. The movement of Met221 sidechain allows the CH2 -H4 folate substrate to bind. The unique topology of its NADH and CH2 -H4 folate binding pockets makes NmMTHFR a promising drug target for the development of new antimicrobial agents that may possess reduced off-target side effects.

OpcA and PorB are novel bactericidal antigens of the 4CMenB vaccine in mice and humans

The ability of Neisseria meningitidis Outer Membrane Vesicles (OMV) to induce protective responses in humans is well established and mainly attributed to Porin A (PorA). However, the contribution of additional protein antigens to protection remains to be elucidated. In this study we dissected the immunogenicity of antigens originating from the OMV component of the 4CMenB vaccine in mice and humans. We collected functional data on a panel of strains for which bactericidal responses to 4CMenB in infants was attributable to the OMV component and evaluated the role of 30 OMV-specific protein antigens in cross-coverage. By using tailor-made protein microarrays, the immunosignature of OMV antigens was determined. Three of these proteins, OpcA, NspA, and PorB, triggered mouse antibodies that were bactericidal against several N. meningitidis strains. Finally, by genetic deletion and/or serum depletion studies, we demonstrated the ability of OpcA and PorB to induce functional immune responses in infant sera after vaccination. In conclusion, while confirming the role of PorA in eliciting protective immunity, we identified two OMV antigens playing a key role in protection of infants vaccinated with the 4CMenB vaccine against different N. meningitidis serogroup B strains.

Trends in Neisseria meningitidis serogroups amongst patients with suspected cerebrospinal meningitis in the meningitis belt of Ghana: a 5-year retrospective study

BackgroundSerogroup A Neisseria meningitidis was the major cause of meningococcal meningitis epidemics in the African meningitis belt before 2010 when the monovalent meningococcal A conjugate vaccine (MenAfriVac) was introduced in the region. Therefore, this study aimed to establish the trends in N. meningitidis serogroups from 2016 to 2020 in Ghana’s meningitis belt.MethodsPolymerase chain reaction (PCR) confirmed laboratory results of suspected cases of cerebrospinal meningitis from January, 2016 to March, 2020 were obtained from the Tamale Public Health Laboratory. The data were subjected to trend analysis using Statistical Package for the Social Sciences version 25. Differences between discrete variables were analyzed using the Cochran–Armitage trend test.ResultsOf the 2,426 suspected cases, 395 (16.3%) were confirmed positive for N. meningitidis using PCR. Serogroup X showed a significant upward trend (P < 0.01), and serogroup W showed a downward trend (P < 0.01). However, no significant trend was observed for any other serogroup.ConclusionThis study showed the emergence of serogroup X, a non-vaccine type, as the predominant N. meningitidis serogroup in the wake of a declining serogroup W in Ghana’s meningitis belt.