Propositive follow-up: Long-term immune responses to the 4CMenB and MenACWY vaccines in people living with HIV.

BACKGROUND: People living with HIV have an increased risk of meningococcal disease. The Propositive trial evaluated co-administration of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in people with HIV. The follow-up trial assessed the immunogenicity of these vaccines at 1.5 and 2.5 years after primary vaccination. METHODS: Participants who completed the parent Propositive trial were invited to the follow-up study. Immunogenicity analysis was performed at 18 and 30 months after primary vaccination. Primary outcome measures were serum bactericidal antibody (SBA) geometric mean titres (GMTs) against three MenB reference strains and the proportion of participants maintaining a protective SBA titre of ≥4 at 18 and 30 months. Secondary outcome measures were SBA GMTs against MenA, C, W, and Y serogroups and the proportion of participants maintaining a protective SBA titre of ≥8 at 18 and 30 months. The trial is registered with Clinicaltrials.gov (NCT042394300). RESULTS: A total of 40 participants aged 22-47 years were enrolled. Geometric mean titres waned by 18 and 30 months but remained higher than pre-vaccination for all MenB strains and MenA, C, W, and Y. In total, 75%-85% of participants retained protective SBA titres by 30 months against individual MenB strains, whereas 68.8% of patients retained protective antibody titres against all three MenB strains. Antibodies against MenC waned more rapidly than did those against MenA, W, and Y. The proportion of participants with protective titres against MenC at 30 months was also lower (46.9%) than that with protective titres against MenA (87.5%), W (78.1%), and Y (87.5%). CONCLUSIONS: Immune responses against MenB in our cohort of people living with HIV at 2.5 years of follow-up were reassuring, with 68.8% of participants retaining protection against all three reference strains. However, responses against MenC were lower than those against MenA, W, and Y serogroups.

The impact of regional disparities on the availability of meningococcal vaccines in the US.

BACKGROUND: In the United States (US), three types of vaccines are available to prevent invasive meningococcal disease (IMD), a severe and potentially fatal infection: quadrivalent conjugate vaccines against serogroups A, C, W, Y (MenACWY), and monovalent vaccines against serogroup B (MenB) as well as a newly licensed pentavalent vaccine (MenABCWY) protecting against serogroup A, B, C, W, and Y. The CDC's Advisory Committee on Immunization Practices (ACIP) routinely recommends MenACWY vaccine for all 11- to 12-year-olds with a booster dose at 16 years. MenB vaccination is recommended based on shared clinical decision-making (SCDM) for 16- to 23-year-olds. Recently, the pentavalent meningococcal vaccine (MenABCWY) was recommended by the ACIP. Meningococcal vaccine uptake is suboptimal across the country, particularly among individuals with lower socioeconomic status (SES), despite these recommendations. The objective of the spatial analyses was to assess the relationship between stocking of MenACWY and MenB vaccines, area-level SES, and state-level policies. METHODS: The number of MenACWY and MenB doses stocked by vaccinators was obtained from IQVIA and the CDC's Vaccine for Children (VFC) program and compiled into a county-level dataset from 2016 to 2019. SES, as measured using the CDC's Social Vulnerability Index (SVI), state-level school recommendations, and universal purchasing programs were among the main county-level covariates included to control for factors likely influencing stocking. Data were stratified by public and private market. Bayesian spatial regression models were developed to quantify the variations in rates of stocking and the relative rates of stocking of both vaccines. RESULTS: After accounting for county-level characteristics, lower SES counties tended to have fewer doses of MenB relative to MenACWY on both public and private markets. Lower SES counties tended to have more supply of public vs. private doses. Universal purchasing programs had a strong effect on the markets for both vaccines shifting nearly all doses to the public market. School vaccination strategy was key for improving stocking rates. CONCLUSIONS: Overall, the results show that MenACWY has greater stock relative to MenB across the US. This difference is exacerbated in vulnerable areas without school entry requirements for vaccination and results in inequity of vaccine availability. Beyond state-level policy and SES differences, SCDM recommendations may be a contributing factor, although this was not directly assessed by our model.

Recognizing the Broader Value of Meningococcal Vaccination: A Matter of Evidence, Ability, or Willingness?

OBJECTIVES: It is widely argued that the value of meningococcal vaccination extends beyond the narrow value elements traditionally considered in health technology assessment. Nevertheless, measuring broader value presents challenges, whereas assessment methods and outcomes vary widely. This article investigates the extent to which the broader value of meningococcal vaccination is recognized, considering the available evidence and decision maker's methodological ability and willingness. METHODS: A targeted literature review informed the classification of broader value elements according to their relevance to meningococcal vaccination and the quality of existing evidence. Focusing on relevant value elements with good evidentiary standards, decision makers' perspectives and methodological ability to consider them were assessed through case studies of health technology assessment of meningococcal B vaccination in England and The Netherlands. RESULTS: Value elements of high relevance to meningococcal vaccination with good quality evidence include caregivers' health gains, patients' lifetime productivity gains, and disease severity. The willingness and methodological ability to incorporate them into value assessments have been mixed. This is attributable to the scope of the value assessment perspective and the use of evaluation methods that do not fully capture broader value. For other broader value elements, evidence gaps are another potential barrier to value demonstration and recognition. CONCLUSIONS: The current evidence base confirms that the value of meningococcal vaccination spans beyond healthcare sector effects to health-related externalities, allocative value, and societal economic benefits. To ensure that the most efficient resource allocation outcomes are achieved, countries should consider how to improve their perspective and methodological ability to assess broader value elements accurately.

Barriers and facilitators to HPV and meningococcal vaccination among men who have sex with men: a qualitative study.

BACKGROUND: Men who have sex with men (MSM) have suboptimal uptake of human papillomavirus (HPV) and meningococcal vaccines. This study examines barriers and facilitators to HPV and meningococcal vaccination among MSM in a large, racially/ethnically diverse, and medically underserved U.S. region. METHODS: In 2020, we conducted five focus groups with MSM living in the Inland Empire, California. Participants discussed (1) their knowledge about and attitudes toward HPV, meningococcal disease, and related vaccines; and (2) factors that would encourage or discourage vaccine uptake. Data were systematically analyzed to identify salient barriers and facilitators to vaccination. RESULTS: Participants (N = 25) had a median age of 29. Most were Hispanic (68%), self-identified as gay (84%), and had college degrees (64%). Key barriers to vaccination included: (1) limited awareness and knowledge about HPV and meningococcal disease, (2) reliance on mainstream healthcare providers for vaccine information, (3) stigma and reluctance to disclose sexual orientation, (4) uncertainty about health insurance coverage and vaccine costs, and (5) distance and time required to access vaccines. Key facilitators to vaccination were: (1) vaccine confidence, (2) perceived severity of HPV and meningococcal disease, (3) bundling vaccination into routine healthcare, and (4) pharmacies as vaccination sites. CONCLUSIONS: Findings highlight opportunities for HPV and meningococcal vaccine promotion, including targeted education and awareness campaigns for MSM, LGBT inclusivity training for healthcare providers, and structural interventions to improve vaccine accessibility.

Outcomes from the Use of Targeted Interventions to Increase Meningococcal Vaccination Rates in a Pediatric Clinic.

BACKGROUND: Meningococcal disease is a life-threatening illness that can cause sequelae such as neurological impairment, hearing loss, seizures, limb amputations, and scarring. Adolescents and young adults are at highest risk for contracting this disease which comes with a case-fatality ratio of 10-15%. Common serogroups in the United States are B, C, W, and Y, which are covered by two separate vaccines administered in a two-dose series. While MenACWY is routinely administered, the booster dose is often missed. Only 21.8% of teens reported receiving the MenB vaccine. While it is not currently part of routine care, recent outbreaks have been caused by serogroup B, prompting the need for increased vaccination rates. METHODS: MenACWY and MenB vaccination rates and demographic information were collected for 16-19-year-old patients in a pediatric clinic. Interventions including staff education, call logs, EMR communications to parents/guardians, and careful chart review were employed. RESULTS: At the time of baseline MenACWY data collection, there were N = 333 subjects between 16 and 19 years of age and N = 335 subjects between 16 and 19 years of age provided for MenB data. Upon completion, there were N = 319 subjects. Comparison of pre- and post-intervention data demonstrated a statistically significant increase in MenACWY series completion from 67.3 to 76.2% (p = 0.035) and a non-statistically significant increase in MenB completion from 6.9 to 10.3% (p = 0.197). CONCLUSIONS: There was a statistically significant improvement in MenACWY but not MenB vaccination rates, indicating a need for more effective measures in addressing low MenB coverage.

Reactive vaccination as control strategy for an outbreak of invasive meningococcal disease caused by Neisseria meningitidis C:P1.5-1,10-8:F3-6:ST-11(cc11), Bergamo province, Italy, December 2019 to January 2020.

In Italy, serogroup C meningococci of the clonal complex cc11 (MenC/cc11) have caused several outbreaks of invasive meningococcal disease (IMD) during the past 20 years. Between December 2019 and January 2020, an outbreak of six cases of IMD infected with MenC/cc11 was identified in a limited area in the northern part of Italy. All cases presented a severe clinical picture, and two of them were fatal. This report is focused on the microbiological and molecular analysis of meningococcal isolates with the aim to reconstruct the chain of transmission. It further presents the vaccination strategy adopted to control the outbreak. The phylogenetic evaluation demonstrated the close genetic proximity between the strain involved in this outbreak and a strain responsible for a larger epidemic that had occurred in 2015 and 2016 in the Tuscany Region. The rapid identification and characterisation of IMD cases and an extensive vaccination campaign contributed to the successful control of this outbreak caused by a hyperinvasive meningococcal strain.

Failure of first meningococcal vaccination in patients with atypical haemolytic uraemic syndrome treated with eculizumab.

BACKGROUND: The C5 complement inhibitor eculizumab is a first-line treatment in atypical haemolytic uraemic syndrome (aHUS). Therapy with eculizumab is associated with a highly increased risk for meningococcal infection. Therefore, vaccination is highly recommended before beginning treatment. Efficacy of quadrivalent meningococcal vaccines (MenACWY) in patients treated with the C5 complement inhibitor eculizumab in aHUS has not yet been determined. METHODS: Patients with aHUS received one dose of a MenACWY conjugate vaccine before eculizumab treatment commenced. Bactericidal titres against meningococcal serogroups A, C, W and Y were determined using baby rabbit complement in 25 patients. RESULTS: Full immune response to meningococcal vaccination was detected in five patients (20%), while seven patients (28%) showed no immune response in any of the tested serogroups. The remaining 13 patients showed incomplete immune response with proof of protective antibody titres for one to three serogroups without perceptible preference for any serogroup. Bactericidal titres after re-vaccination were available for 17 patients. Nine patients with incomplete immune response after first vaccinations showed protective antibody titres for all serogroups after re-vaccination. Kidney function had improved in >50% of patients at the time of re-vaccination compared with the time of first vaccination and immunosuppressive therapy was only applied to re-vaccinated patients following kidney transplantation. CONCLUSIONS: Immunogenicity of first quadrivalent meninongococcal vaccination is insufficient in patients with aHUS. Booster response is promising, but incomplete. Therefore, establishing antibiotic prophylaxes seems pivotal.

Serologic response to meningococcal vaccination in patients with paroxysmal nocturnal hemoglobinuria (PNH) chronically treated with the terminal complement inhibitor eculizumab.

Eculizumab is indicated for the therapy of patients with symptomatic paroxysmal nocturnal hemoglobinuria (PNH). Due to inhibition of terminal complement cascade, patients on eculizumab are susceptible to Neisseria meningitidis infections. The two mainstays to reduce the risk of infection are vaccination and antibiotic prophylaxis. In this retrospective study, serologic response was analyzed after vaccination with a meningococcal vaccine in 23 PNH patients (median age 36 years; range 25 - 88 years; 15 males, 8 females) by measuring serum bactericidal assay (SBA) using rabbit complement (rSBA) titers against meningococcal serogroups A, C, W, and Y. Serologic protection was defined by an rSBA titer ≥1:8. Forty-three percent (10/23) were vaccinated more than once due to chronic eculizumab treatment. Overall serologic response for the meningococcal serogroups was A: 78% (18/23), C: 87% (20/23), W: 48% (11/23), and Y: 70% (16/23). No meningococcal infections have been observed. As immunological response to vaccines varies, the use of serologic response analyses is warranted. Re-vaccination with a tetravalent conjugate vaccine under eculizumab therapy every 3 years is essential or should be based on response rates. If meningococcal infection is suspected, standby therapy with ciprofloxacin and immediate medical evaluation are recommended. The novel vaccines covering serogroup B may even further reduce the risk for infection.

Nasal Inoculation of the Commensal Neisseria lactamica Inhibits Carriage of Neisseria meningitidis by Young Adults: A Controlled Human Infection Study.

BACKGROUND: Herd protection by meningococcal vaccines is conferred by population-level reduction of meningococcal nasopharyngeal colonization. Given the inverse epidemiological association between colonization by commensal Neisseria lactamica and meningococcal disease, we investigated whether controlled infection of human volunteers with N. lactamica prevents colonization by Neisseria meningitidis. METHODS: In a block-randomized human challenge study, 310 university students were inoculated with 10(4) colony-forming units of N. lactamica or were sham-inoculated, and carriage was monitored for 26 weeks, after which all participants were reinoculated with N. lactamica and resampled 2 weeks later. RESULTS: At baseline, natural N. meningitidis carriage in the control group was 22.4% (36/161), which increased to 33.6% (48/143) by week 26. Two weeks after inoculation of N. lactamica, 33.6% (48/143) of the challenge group became colonized with N. lactamica. In this group, meningococcal carriage reduced from 24.2% (36/149) at inoculation to 14.7% (21/143) 2 weeks after inoculation (-9.5%; P = .006). The inhibition of meningococcal carriage was only observed in carriers of N. lactamica, was due both to displacement of existing meningococci and to inhibition of new acquisition, and persisted over at least 16 weeks. Crossover inoculation of controls with N. lactamica replicated the result. Genome sequencing showed that inhibition affected multiple meningococcal sequence types. CONCLUSIONS: The inhibition of meningococcal carriage by N. lactamica is even more potent than after glycoconjugate meningococcal vaccination. Neisseria lactamica or its components could be a novel bacterial medicine to suppress meningococcal outbreaks. This observation explains the epidemiological observation of natural immunity conferred by carriage of N. lactamica. CLINICAL TRIALS REGISTRATION: NCT02249598.

Quantifying Stated Preferences for Meningococcal Vaccines Among Adolescents/Young Adults and Parents of Adolescents in the United States: A Discrete Choice Experiment.

INTRODUCTION: Invasive meningococcal disease (IMD) is a severe and life-threatening disease. In the United States (US), vaccine coverage with MenACWY and MenB meningococcal vaccines is suboptimal among adolescents/young adults aged 16-23 years. A combined meningococcal vaccine (MenABCWY) could increase convenience (e.g., fewer injections) and improve coverage. The objective was to quantify preferences for hypothetical meningococcal vaccine profiles among adolescents/young adults and parents. METHODS: An online discrete choice experiment was conducted among 16- to 23-year-olds, and parents of 16- to 18-year-olds. Attributes (3 × 4) and levels (1 × 2) were based on the literature and focus groups. Participants made ten pair-wise forced trade-off choices, systematically varied using a D-optimal design. Random parameter logit quantified the relative importance of vaccination attributes and estimated the trade-offs. Differences in preferences by subgroups were assessed. RESULTS: Totals of 300 adolescents and young adults (median age 20 years) and 300 parents (median age 46 years) completed the survey. Overall, 89.6% of 16- to 23-year-olds and 69.1% of parents preferred a simplified hypothetical meningococcal vaccination profile, e.g., with fewer injections (3 vs. 4) and fewer healthcare provider (HCP) visits (2-3 vs. 4). Having HCP advice and clear Centers for Disease Control and Prevention recommendations impacted vaccination choice, with both groups reporting high trust in HCP information (83.3% among 16- to 23-year-olds; 98.7% among parents). Barriers to vaccination included lack of HCP advice or awareness of meningococcal vaccines, and income level and out-of-pocket costs for parents. CONCLUSIONS: Adolescents/young adults and parents demonstrated a significant preference for a meningococcal vaccine that is more convenient (such as combined MenABCWY). Parents' vaccination preferences differed by income level and out-of-pocket costs, suggesting financial barriers to vaccination may exist which could result in IMD prevention inequalities. Findings from this study provide important information to support patient-facing informed policy discussions. A simplified vaccination schedule and strong recommendation could help improve vaccine uptake, schedule compliance, disease prevention, and reduce inequalities in IMD risk and prevention. A graphical abstract is available with this article.

Expert Perspectives on the Vaccination of Individuals Who Are at Increased Risk of Meningococcal Disease Due to Medical Conditions: A Podcast.

Patients with functional or anatomic asplenia, including sickle cell anemia; complement component deficiency; or human immunodeficiency virus (HIV) infection have a significantly increased risk of developing meningococcal disease. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommends vaccination with a quadrivalent meningococcal conjugate vaccine against serogroups A, C, W, and Y (MenACWY) for individuals 2 months of age or older who are diagnosed with functional or anatomic asplenia, complement component deficiency, or HIV infection. Vaccination with a meningococcal vaccine against serogroup B (MenB) is also recommended for individuals 10 years of age or older who are diagnosed with functional or anatomic asplenia or complement component deficiency. Despite these recommendations, recent studies have shown that vaccination coverage in these populations is low. In this podcast, the authors discuss the challenges for implementing vaccine recommendations for individuals with medical conditions at increased risk of developing meningococcal disease and discuss strategies to increase coverage. Suboptimal vaccination rates could be addressed by better educating healthcare providers about recommendations for MenACWY and MenB vaccines in individuals at increased risk, increasing awareness of low vaccination coverage, and tailoring the education to the needs of particular healthcare providers and their respective patient populations. Barriers to vaccination could also be removed by administering vaccines at alternative sites of care, bundling preventative services, and implementing vaccination reminder systems that are tied to immunization information systems.

Invasive meningococcal disease is rare, but serious. Some people are at increased risk because of their medical conditions, including: People without a working spleen People with reduced immune function due to conditions known as complement component deficiencies People living with human immunodeficiency virus (HIV) infection Vaccines are available to prevent meningococcal disease, and these vaccines are recommended for healthy young people as well as for people at increased risk. Studies have shown that a low proportion of people at increased risk has been vaccinated. Strategies are needed to make sure more people in these groups get vaccinated. We suggest educating healthcare providers about the recommended vaccines and making it easier for people to get vaccinated by, for example, providing vaccines in places they might visit more often than a doctor's office.

The Impact of Social Determinants of Health on Meningococcal Vaccination Awareness, Delivery, and Coverage in Adolescents and Young Adults in the United States: A Systematic Review.

Vaccines remain a fundamental intervention for preventing illness and death. In the United States, suboptimal vaccine uptake in adolescents and young adults has been observed for meningococcal conjugate (MenACWY) and serogroup B meningococcal (MenB) vaccines, particularly among marginalized communities, despite current recommendations by the Advisory Committee on Immunization Practices. A systematic literature search was conducted in the MEDLINE and MEDLINE In-Process, Embase, Cochrane, PsychInfo, and CINAHL databases to identify both drivers of, and barriers to, MenACWY and MenB vaccine uptake in adolescents and young adults. A total of 34 of 46 eligible studies that presented outcomes stratified by race/ethnicity, geography, and socioeconomic status were selected for review. Results showed MenACWY and MenB vaccination coverage in adolescents and young adults is impacted by racial/ethnic, socioeconomic, and geographic disparities. Gaps also exist in insurance for, or access to, these vaccines in adolescents and young adults. Moreover, there was variability in the understanding and implementation of the shared decision-making recommendations for the MenB vaccine. Disease awareness campaigns, increased clarity in accessing all meningococcal vaccines, and further research on the relationships between measures of marginalization and its impact on vaccine coverage in adolescents and young adults are needed to reduce the incidence of severe infections.

Meningococcal A conjugate vaccine coverage in the meningitis belt of Africa from 2010 to 2021: a modelling study.

Background: As of the end of 2021, twenty-four countries in the African meningitis belt have rolled out mass campaigns of MenAfriVac®, a meningococcal A conjugate vaccine (MACV) first introduced in 2010. Twelve have completed introduction of MACV into routine immunisation (RI) schedules. Although select post-campaign coverage data are published, no study currently comprehensively estimates MACV coverage from both routine and campaign sources in the meningitis belt across age, country, and time. Methods: In this modelling study, we assembled campaign data from the twenty-four countries that had introduced any immunisation activity during or before the year 2021 (Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Côte d'Ivoire, Democratic Republic of the Congo, Ethiopia, Eritrea, the Gambia, Ghana, Guinea, Guinea Bissau, Kenya, Mali, Mauritania, Niger, Nigeria, Senegal, South Sudan, Sudan, Togo and Uganda) via WHO reports and RI data via systematic review. Next, we modelled RI coverage using Spatiotemporal Gaussian Process Regression. Then, we synthesized these estimates with campaign data into a cohort model, tracking coverage for each age cohort from age 1 to 29 years over time for each country. Findings: Coverage in high-risk locations amongst children aged 1-4 in 2021 was estimated to be highest in Togo with 96.0% (95% uncertainty interval [UI] 92.0-99.0), followed by Niger with 87.2% (95% UI 85.3-89.0) and Burkina Faso, with 86.4% (95% UI 85.1-87.6). These countries had high coverage values driven by an initial successful mass immunisation campaign, followed by a catch-up campaign, followed by introduction of RI. Due to the influence of older mass vaccination campaigns, coverage proportions skewed higher in the 1-29 age group than the 1-4 group, with a median coverage of 82.9% in 2021 in the broader age group compared to 45.6% in the narrower age group. Interpretation: These estimates highlight where gaps in immunisation remain and emphasise the need for broader efforts to strengthen RI systems. This methodological framework can be applied to estimate coverage for any vaccine that has been delivered in both routine and supplemental immunisation activities. Funding: Bill and Melinda Gates Foundation.

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

INTRODUCTION: The 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 METHODS: Serum 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). RESULTS: A 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. CONCLUSION: Unvaccinated 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.

An Overview of Meningococcal Disease's Recent Diagnostic and Treatment Model.

In healthy people, Neisseria meningitidis (the meningococcus) is a typical component of the nasopharyngeal microbiome, but in those who are susceptible, it can cause septicemia and meningitis. This section gives a general overview of the meningococcus types and the sickness induced by N. meningitidis. Evaluate genes for phase-changeable adhesions, virulence factors, and effective colonization of the human host. In our final section, we summarize the evolution of meningococcal vaccines and their current state while emphasizing the value of ongoing molecular research into the pathogen's epidemiology and structural analysis of its antigens. IMD is a major global source of morbidity and mortality and a public health concern. IMD can manifest as an epidemic with breakouts or as an endemic illness with sporadic instances. There are 13 serogroups of Neisseria meningitis strains, however, only five (A, B, C, W-135, and Y) account for the majority of IMD globally. IMD poses a risk to people of all ages, although young children and teenagers are especially at risk. Meningitis and septicemia are the two clinical symptoms of IMD that occur most frequently, while both clinical presentations can occasionally exist. Age might affect the clinical pattern; in early childhood, the clinical manifestations could be more subtle, and the diagnosis may be trickier than in older kids or teenagers. In 4.3-11.2% of instances, there are sequelae, and death occurs in 6-10% of cases. Although vaccination remains the most effective method of preventing meningococcal disease, it is crucial to identify children with meningococcal infection as soon as possible to begin systemic antibiotic therapy. The prevalence of the disease has decreased as a result of the recent introduction of various meningococcal vaccinations on a global scale. Increasing meningococcal disease vaccination rates, keeping an eye on IMD, and creating a special vaccine that can protect against all of the major meningococcal strains should be the priorities for the upcoming few years.

Sex-Related Differences in the Immune Response to Meningococcal Vaccinations During Adolescence.

Background: Immune responses to pediatric vaccinations have been reported to differ according to sex. Such sex-differential responses may become more pronounced during adolescence due to hormonal differences. We investigated whether the vaccine response following primary vaccination against meningococcal serogroup A (MenA), MenW and MenY and booster vaccination against MenC differed between girls and boys using data from two clinical studies. Methods: Children aged 10, 12, and 15 years, who had been primed with MenC vaccination between 14 months and 6 years of age, received a booster MenC vaccination or MenACWY vaccination. Polysaccharide-specific IgG concentrations and functional antibody titers [determined with the serum bactericidal antibody (SBA) assay] were measured at baseline, 1 month, 1 year, and 3 years (only MenC group) after vaccination. We calculated geometric mean concentrations and titers (GMC and GMT) ratios for girls vs. boys adjusted for age group. Additionally, we compared the proportion protected individuals between girls and boys at all timepoints. Results: This study included 342 girls and 327 boys from two clinical trials. While MenAWY antibody levels did not differ consistently 1 month after vaccination, all GMC- and GMT-ratios were in favor of girls 1 year after vaccination [range: 1.31 (1.02-1.70) for MenA IgG to 1.54 (1.10-2.16) for MenW IgG]. Overall, MenC antibody levels were slightly higher in girls at all postvaccination timepoints (GMC- and GMT-ratios: 1.16/1.17 at 1 month, 1.16/1.22 at 1 year and 1.12/1.15 3 years postvaccination). Higher MenC antibody levels were observed in 12- and 15-year-old girls compared to boys of the same age, whereas 10-year-old boys and girls had similar antibody levels. The percentage of participants protected (SBA titer ≥ 8) was very high (95-100%) at all timepoints, and did not differ significantly between boys and girls. Conclusion: Antibody responses were higher in girls than in boys for all serogroups at most timepoints after primary MenAWY vaccination and booster MenC vaccination. The differences in average titers were however small and the percentage participants with protective titers was very high for both sexes.

Evolving strategies for meningococcal vaccination in Europe: Overview and key determinants for current and future considerations.

Invasive meningococcal disease (IMD) is a life-threatening, unpredictable condition. Vaccines are available against 5 of the 6 meningococcal serogroups (Men) accounting for nearly all IMD cases worldwide; conjugate monovalent MenC, quadrivalent MenACWY, and protein-based MenB vaccines are commonly used. We provide a comprehensive overview of the evolution of meningococcal vaccination strategies employed in national immunization programmes (NIPs) and their impact on IMD incidence in Europe. A more in-depth description is given for several countries: the United Kingdom (UK), the Netherlands, Greece, Italy, and Ireland. We searched European health authorities' websites and PubMed. Various vaccines and immunization schedules are used in 21 NIPs. Most countries implement MenC vaccination in infants, MenACWY in adolescents, and a growing number, MenB in infants. Only Malta has introduced MenACWY vaccination in infants, and several countries reimburse immunization of toddlers. The UK, Italy, Ireland, Malta, Andorra, and San Marino recommend MenB vaccination in infants and MenACWY vaccination in adolescents, targeting the most prevalent serogroups in the most impacted age groups. Main factors determining new vaccination strategies are fluctuating IMD epidemiology, ease of vaccine implementation, ability to induce herd protection, favorable benefit-risk balance, and acceptable cost-effectiveness. Since 1999, when the UK introduced MenC vaccination, the reduction in IMD incidence has been gradually enhanced as other countries adopted routine meningococcal vaccinations. Meningococcal vaccination strategies in each country are continually adapted to regional epidemiology and national healthcare priorities. Future strategies may include broader coverage vaccines when available (e.g., MenABCWY, MenACWY), depending on prevailing epidemiology.

Overview of meningococcal epidemiology and national immunization programs in children and adolescents in 8 Western European countries.

Background: In Europe, meningococcal (Men) vaccines are available against 5 of the 6 serogroups responsible of nearly all cases of invasive meningococcal disease (IMD). Meningococcal vaccination has been introduced in the national immunization programs (NIPs) for children and adolescents of numerous European countries, but with no consistent strategy across countries. Objectives: To describe IMD epidemiology, NIPs, and vaccination coverage rates (VCRs) in children and adolescents in 8 Western European countries. Methods: Epidemiological data (from 1999 to 2019), NIPs regarding meningococcal vaccination status, and VCRs were collected from the European Centre for Disease Prevention and Control (ECDC) and/or national websites. Results: MenB was the most common serogroup. In Belgium, Spain, France, the Netherlands, the United Kingdom (UK), and Portugal, incidence was greater for MenW than MenC. In 2019, MenB risk was covered in 2 countries (Italy, UK). MenC risk was covered in all countries, via MenC only (countries: N = 3), MenACWY only (N = 2), or MenC (infants/children) and MenACWY (adolescents) (N = 3) vaccination. VCRs were higher in children than adolescents. Conclusion: Our study confirmed the diversity of NIPs, including in neighboring European countries with similar factors like economic resources and epidemiological risk, thus indicating that other factors underlie NIPs. Convergence toward a more common immunization program including MenACWY and MenB vaccination would promote equity and safe travel regarding infectious diseases for young people, and possibly improve the understanding of vaccination by patients and healthcare professionals.

Post-licensure observational safety study after meningococcal B vaccine 4CMenB (Bexsero) vaccination within the routine UK immunisation program.

The study investigated the safety of 4-component meningococcal serogroup B vaccination (4CMenB) in routine care. 4CMenB exposure and seizures, febrile seizures and Kawasaki disease were identified from The Health Improvement Network (THIN) database of UK electronic primary healthcare records, 2015-2018. A self-controlled case series analysis was completed. Anaphylaxis, Guillain-Barré syndrome and acute disseminated encephalomyelitis were secondary outcomes. A total of 107,231 children aged 1-18 months received ≥1 doses of 4CMenB vaccination. Most 4CMenB exposure (93%) was on the same day as other vaccines within a complete national immunisation program stage. With day 0 as day of vaccination, 43 seizures occurred in days 0-6 after 239,505 doses, and 23 febrile seizures occurred in days 0-6, and 4 Kawasaki disease cases in days 1-28 after 194,929 4CMenB doses. Adjusted incidence rate ratios including all 4CMenB exposures were 1.43 (95%CI: 1.02-2.02) for seizures and 1.72 (95%CI: 1.08-2.75) for febrile seizures. There were insufficient cases to model Kawasaki disease, and no cases of the secondary outcomes in risk periods when they may be associated with the vaccination. This study shows few cases of the outcomes after vaccination including 4CMenB with an increased risk of seizures and febrile seizures. It is not possible to attribute the finding to one specific vaccination as the majority of 4CMenB was given with other vaccinations. Trial registration: NA.