Meningococcal disease is highly transmissible, life-threatening and leaves significant sequelae in survivors. Every year, India, which has a plethora of risk factors for meningococcal disease, reports around 3000 endemic cases. However, the overall disease burden and serogroup distribution are unknown, creating a setting of general disease negligence and unawareness. Vaccination with quadrivalent meningococcal conjugate vaccine A, C, W, and Y is only recommended for high-risk children, and there is no overall guidance for meningococcal serogroup B (MenB) vaccination. MenB vaccines, which recently have been licensed in many countries but not in India, have significantly aided the fight against meningococcal disease. However, these MenB vaccines are not available in India. An Expert Consensus Group meeting was held with leading meningococcal disease experts to better understand the current disease epidemiology, particularly serogroup B, the prevalence gaps, and feasible ways to bridge them. The proceedings are presented in this paper.

Vaccination is an effective strategy to combat invasive meningococcal disease (IMD). Vaccines against the major disease-causing meningococcal serogroups are available; however, development of vaccines against serogroup B faced particular challenges, including the inability to target traditional meningococcal antigens (i.e. polysaccharide capsule) and limited alternative antigens due to serogroup B strain diversity. Two different recombinant, protein-based, serogroup B (MenB) vaccines that may address these challenges are currently available. These vaccines have been extensively evaluated in pre-licensure safety and immunogenicity trials, and recently in real-world studies on effectiveness, safety, and impact on disease burden.
This review provides healthcare professionals, particularly pediatricians, an overview of currently available MenB vaccines, including development strategies and evaluation of coverage.
Overall, recombinant MenB vaccines are valuable tools for healthcare professionals to protect patients against IMD. Their development required innovative design approaches that overcame challenging hurdles and identified novel protein antigen targets; however, important distinctions in the approaches used in their development, evaluation, and administration exist and many unanswered questions remain. Healthcare providers frequently prescribing MenB vaccines are challenged to keep abreast of these differences to ensure patient protection against this serious disease.

Meningococcal serogroup B (MenB) accounts for an important proportion of invasive meningococcal disease (IMD). The 4-component vaccine against MenB (4CMenB) is composed of factor H binding protein (fHbp), neisserial heparin-binding antigen (NHBA), Neisseria adhesin A (NadA), and outer membrane vesicles of the New Zealand strain with Porin 1.4. A meningococcal antigen typing system (MATS) and a fully genomic approach, genetic MATS (gMATS), were developed to predict coverage of MenB strains by 4CMenB. We characterized 520 MenB invasive disease isolates collected over a 5-year period (January 2007-December 2011) from all Australian states/territories by multilocus sequence typing and estimated strain coverage by 4CMenB. The clonal complexes most frequently identified were ST-41/44 CC/Lineage 3 (39.4%) and ST-32 CC/ET-5 CC (23.7%). The overall MATS predicted coverage was 74.6% (95% coverage interval: 61.1%-85.6%). The overall gMATS prediction was 81.0% (lower-upper limit: 75.0-86.9%), showing 91.5% accuracy compared with MATS. Overall, 23.7% and 13.1% (MATS) and 26.0% and 14.0% (gMATS) of isolates were covered by at least 2 and 3 vaccine antigens, respectively, with fHbp and NHBA contributing the most to coverage. When stratified by year of isolate collection, state/territory and age group, MATS and gMATS strain coverage predictions were consistent across all strata. The high coverage predicted by MATS and gMATS indicates that 4CMenB vaccination may have an impact on the burden of MenB-caused IMD in Australia. gMATS can be used in the future to monitor variations in 4CMenB strain coverage over time and geographical areas even for non-culture confirmed IMD cases.

Serogroup B meningococci (MenB) remain a prominent cause of invasive meningococcal disease (IMD). The protein-based multicomponent 4CMenB and the bivalent MenB-FHbp are the only currently available vaccines against MenB-caused IMD. Efficacy studies are not possible, due to the low incidence of IMD. Therefore, the vaccines\' immunogenicity has been evaluated against several target strains chosen to quantify complement-mediated killing induced by each vaccine component in the serum bactericidal antibody assay. However, due to the wide genetic diversity and different expression levels of vaccine antigens across MenB strains, vaccine performance may differ from one strain to another. Here, we review the methods used to predict MenB strain coverage for 4CMenB and MenB-FHbp. Phenotypic assays such as the meningococcal antigen typing system (MATS, 4CMenB-specific) and the flow cytometric meningococcal antigen surface expression assay (MEASURE; MenB-FHbp-specific) were developed. Genomic approaches are also available, such as genetic MATS (gMATS) and the Bexsero antigen sequence type (BAST) scheme, both 4CMenB-specific. All methods allow tentative predictions of coverage across MenB strains, including that afforded by each vaccine antigen, and are rapid and reproducible. Real-world data on vaccine effectiveness are needed to confirm predictions obtained by these methods.

BACKGROUND: Two phase 3 studies in adolescents and young adults demonstrated that MenB-FHbp, a meningococcal serogroup B (MenB) vaccine, elicits protective immune responses after 2 or 3 doses based on serum bactericidal antibody assays using human complement (hSBA) against 4 primary and 10 additional diverse, vaccine-heterologous MenB test strains. Lower limits of quantitation (LLOQs; titers 1:8 or 1:16; titers ≥ 1:4 correlate with protection) were used to evaluate responses to individual strains and all 4 primary strains combined (composite response). A post hoc analysis evaluated percentages of subjects with protective responses to as many as 8 strains combined (4 primary plus additional strains).
METHODS: Immune responses were measured using hSBAs against 4 primary strains in adolescents (n = 1509, MenB-FHbp; n = 898, hepatitis A virus vaccine/saline) and young adults (n = 2480, MenB-FHbp; n = 824, saline) receiving MenB-FHbp or control at 0, 2, and 6 months. Ten additional strains were evaluated in subsets of subjects from approximately 1800 MenB-FHbp recipients across both studies. Percentages of subjects with hSBA titers ≥ LLOQ for different numbers of primary strains or primary plus additional strains combined (7 or 8 strains total per subset) were determined before vaccination, 1 month post-dose 2, and 1 month post-dose 3.
RESULTS: Across the panel of primary plus additional strains, at 1 month post-dose 3, titers ≥ LLOQ were elicited in 93.7-95.7% of adolescents and 91.7-95.0% of young adults for ≥ 5 test strains combined and in 70.5-85.8% of adolescents and 67.5-81.4% of young adults for ≥ 7 strains combined. Among adolescents, 99.8%, 99.0%, 92.8%, and 82.7% had titers ≥ LLOQ against at least 1, 2, 3, and all 4 primary strains, respectively; corresponding percentages for young adults were 99.7%, 97.7%, 94.0%, and 84.5%.
CONCLUSIONS: Results support the ability of MenB-FHbp to provide broad coverage against MenB strains expressing diverse FHbp variants.
BACKGROUND: ClinicalTrials.gov identifiers NCT01830855, NCT01352845.

BACKGROUND: Meningococcal serogroup B (MenB) is the most common cause of invasive meningococcal disease (IMD) in the United States. The US Advisory Committee on Immunization Practices (ACIP) recommends vaccination of healthy adolescents against MenB based on shared clinical decision-making (Category B recommendation). This survey assessed factors associated with MenB vaccine awareness, utilization, and interest among parents/guardians of US adolescents.
METHODS: Survey participants were identified in 2016 through KnowledgePanel®, an online random sample of US households; population-based weighting methodology was used to ensure data reflected a demographically representative population sample. Adults with ≥1 dependent aged 16-19 years were eligible and completed an online questionnaire. Respondents were grouped in terms of MenB vaccination of their child as: 1) vaccinated, 2) intending to vaccinate, 3) MenB vaccine-unaware, or 4) vaccine-aware but not intending to vaccinate. Univariate and multivariate analyses were used to identify factors influencing MenB vaccine awareness and utilization; univariate analyses used the weighted proportion of each group or weighted means, and multivariate analyses used logistic regression models based on the weighted study sample of each group.
RESULTS: Six hundred nineteen parents/guardians participated, corresponding to 26,266,700 members of the US population after weighting. MenB vaccine awareness was significantly associated with parent race and sex. Specifically, 57% of parents were unaware of MenB vaccines, and there was significantly higher lack of awareness among males and those of Hispanic or non-White ethnicity. In addition, 36% of unaware parents/guardians were interested in and seeking MenB vaccine information from their healthcare provider (HCP), and there was higher interest among parents of Hispanic ethnicity. \'Vaccinated/intending to vaccinate\' versus \'not intending to vaccinate\' and \'vaccinated\' versus \'intending to vaccinate\' were both strongly associated with whether an HCP had recommended vaccination (odds ratios, 4.81 [95% CI 2.46, 9.35] and 5.66 [95% CI 2.46, 12.87], respectively).
CONCLUSIONS: Racial and socioeconomic disparities exist in the awareness and utilization of MenB vaccines among parents/guardians of US adolescents. HCP discussion and recommendation are critical catalysts for MenB vaccination and underscore the need to accurately interpret and implement the shared clinical decision-making (Category B) recommendation.

The C5 complement inhibitor eculizumab is first-line treatment in atypical hemolytic uremic syndrome (aHUS) going along with a highly increased risk of meningococcal infections. Serogroup B meningococci (MenB) are the most frequently encountered cause for meningococcal infections in Europe. Efficacy of the protein-based MenB-vaccine Bexsero in aHUS has not been determined and testing is only possible in patients off-treatment with eculizumab as a human complement source is required.
Patients with aHUS were vaccinated with two doses of the protein-based MenB-vaccine Bexsero. Serum bactericidal antibody (SBA) titers against factor H binding protein (fHbp) of MenB were determined in 14 patients with aHUS off-treatment with eculizumab.
Only 50% of patients showed protective human serum bactericidal antibody (hSBA) titers (≥1:4) against MenB following two vaccinations. Bactericidal antibody titers were relatively low (≤1:8) in three of seven patients with protective titers. While 71% of patients were on immunosuppressive treatment for either thrombotic microangiopathy or renal transplantation at either first or second vaccination, all four patients not receiving any immunosuppressive treatment showed protective bactericidal antibody response. Time between second vaccination and titer measurement was not significantly different between patients with protective titers compared with those with non-protective titers, while time between first and second vaccination was significantly longer in patients with protective titers going along with a tendency for reduction in immunosuppressive treatment.
Efficacy of vaccination against MenB is insufficient in patients with aHUS. Response to vaccination seems to be hampered by immunosuppression. Therefore, implementation of adequate antibiotic prophylaxis seems pivotal.

Introduction: Adolescents and young adults are the primary reservoirs and transmitters of meningococci. In the US, meningococcal serogroup B (MenB) disease predominates over A, C, W, and Y; ACIP-recommended MenACWY and MenB vaccines are available. We investigated invasive meningococcal disease (IMD) burden and vaccination among non-college adolescents.Methods: IMD incidence by college attendance status and vaccination rates were analyzed using publicly available surveillance data.Results: 64/158 IMD cases occurred in non-college 18-24-year-olds during 2015-2017. Among non-college cases, the MenACWY vaccination rates were 38%-57% vs 90%-100% among college cases when vaccination status was known; MenB vaccination was 0% vs 0%-7%, respectively. In 2018, 17.2% of all 17-year-olds received ≥1 dose of multidose MenB vaccines; ≤50% completed the series.Conclusion: Meningococcal vaccination is emphasized for college-bound adolescents, but non-college adolescents bear much of the disease burden. Low vaccine receipt preserves their risk, underscoring the need to protect all adolescents through vaccination.

The multicomponent meningococcal serogroup B vaccine, 4CMenB, has demonstrated effectiveness in preventing invasive MenB disease in infants and in controlling MenB outbreaks. The need for/timing of additional booster doses is not yet established. We reviewed eight studies that evaluated antibody persistence and booster following primary 4CMenB vaccination of infants, children, adolescents, and young adults. Putative seroprotective hSBA titers for ≥1 vaccine antigen were maintained by 76-100% of children 24-36 months after priming during infancy and in 84-100% after priming in the second year of life. hSBA levels were higher in vaccinees at 4 and 7.5 years following priming during adolescence than in vaccine-naïve individuals of a similar age. Antibodies persisted at higher levels to NHBA and NadA than to PorA or fHbp. Booster vaccination induced robust anamnestic responses, demonstrating effective priming by 4CMenB across age-groups. These data can inform decision-making to optimize vaccination strategies.

Meningococcal serogroup B (MenB) has become the main cause of invasive meningococcal disease in industrialized countries in recent years. The diversity of MenB strains and poor immunogenicity of the MenB capsular polysaccharide have made vaccine development challenging. Two MenB vaccines, including factor H binding protein (fHbp) as a major antigenic component, are now licensed for use. In addition to fHbp variant 1, the multicomponent vaccine 4CMenB contains neisserial heparin binding antigen, Neisseria adhesin A, and outer membrane vesicles containing porin A. The vast majority of circulating MenB strains contain genes encoding at least one 4CMenB component and many express genes for more than one vaccine antigen. Recent studies have suggested that serum bactericidal activity is enhanced against strains that express two or more vaccine antigens. Bacterial killing may also occur when antibodies to vaccine components are collectively present at levels that would individually be sub-lethal. The evaluation of immune responses to separate vaccine components does not take cooperative activity into account and may underestimate the overall protection. Available data on 4CMenB effectiveness indicate that this multicomponent vaccine affords broad coverage and protection against MenB disease. 4CMenB also has the potential to protect against disease caused by non-MenB meningococci and Neisseria gonorrhoeae.