BACKGROUND: Many immunization programs in Europe recommend quadrivalent meningococcal vaccinations, which are often administered concomitantly with other vaccines. We compared the immune response of a tetanus toxoid conjugated quadrivalent meningococcal vaccine (MenACYW-TT, MenQuadfi®) with another quadrivalent meningococcal conjugate vaccine (MCV4-TT; Nimenrix®) when administered alone or concomitantly with Tdap-IPV and 9vHPV vaccines in adolescents.
METHODS: In this phase IIIb trial, healthy adolescents (MenC-naïve or MenC-primed before 2 years of age) from Spain, Italy, Hungary, and Singapore were randomized in a 3:3:2 ratio to receive either MenACYW-TT or MCV4-TT alone, or MenACYW-TT concomitantly with 9vHPV and Tdap-IPV. The primary objective was to demonstrate the non-inferiority of the seroprotection rate (human serum bactericidal assay [hSBA] titer ≥ 1:8) to serogroups A, C, W, and Y 30 days post-vaccination with a single dose of MenACYW-TT or MCV4-TT. Secondary objectives included describing hSBA titers for the four serogroups before and 1 month following vaccination and according to MenC priming status.
RESULTS: A total of 463 participants were enrolled (MenACYW-TT, n = 173; MCV4-TT, n = 173; MenACYW-TT/9vHPV/Tdap-IPV n = 117). Non-inferiority based on seroprotection was demonstrated for MenACYW-TT versus MCV4-TT for all serogroups. Immune responses were comparable whether MenACYW-TT was administered alone or concomitantly with Tdap-IPV and 9vHPV. Post-vaccination hSBA GMTs were higher in MenACYW-TT vs. MCV4-TT for serogroups C, Y, and W and comparable for serogroup A. The percentages of participants with an hSBA vaccine seroresponse were higher in MenACYW-TT vs. MCV4-TT for all serogroups. For serogroup C, higher GMTs were observed in both MenC-naïve or -primed participants vaccinated with MenACYW-TT vs. MCV4-TT. Seroprotection and seroresponse were higher in MenC-naïve participants vaccinated with MenACYW-TT vs. MCV4-TT and comparable in MenC-primed. The safety profiles were comparable between groups and no new safety concerns were identified.
CONCLUSIONS: These data support the concomitant administration of MenACYW-TT with 9vHPV and Tdap-IPV vaccines in adolescents.
BACKGROUND: Clinicaltrials.gov, NCT04490018; EudraCT: 2020-001665-37; WHO: U1111-1249-2973.
MenACYW conjugate vaccine has been made to protect against meningococcal disease caused by four common types of bacteria (germs) called Neisseria meningitidis (or meningococcus), A, C, W, and Y. Many people, particularly adolescents, have the germs of this disease in their nose or throat, and therefore may develop the disease or transmit the bacteria to other people. Hence, adolescent meningococcal vaccination against serogroups ACWY is increasingly recommended in several countries. This study assessed the immune response to these serogroups in healthy adolescents after one dose of MenACYW conjugate vaccine or Nimenrix®, a meningococcal licensed vaccine. Moreover, the immune response and safety were assessed when the vaccines were given alone or when given concomitantly with other adolescent vaccines, including the human papillomavirus (9vHPV) and tetanus, diphtheria, pertussis, and poliomyelitis (Tdap-IPV) vaccines. A total of 463 adolescents (aged 10–17 years) participated in this study and received either MenACYW or Nimenrix® alone, or MenACYW concomitantly with 9vHPV and Tdap-IPV vaccine. The immune response induced by MenACYW was as good as the immune response induced by Nimenrix®, and when given alone or concomitantly with 9vHPV and Tdap IPV vaccines. None of the participants experienced any serious side effects of any vaccine. The most common non-serious side effects were injection site pain, muscle pain, and headache. These data support the use of MenACYW in adolescents, with or without concomitant administration with 9vHPV and Tdap-IPV, which may help to increase the number of adolescents vaccinated.

Background Invasive meningococcal disease (IMD) is a bacterial infection caused by Neisseria meningitidis, which primarily affects the meninges, with a high incidence in young children. The most effective technique for preventing IMD is vaccination, which has been available for over 40 years through meningococcal polysaccharide capsule-containing vaccines. This study aims to assess the parental knowledge of meningococcal disease and vaccination in the Makkah region of Saudi Arabia. Methodology A cross-sectional study was conducted between September and December 2023 among 597 parents in the Makkah region using a validated online survey. The collected data were analyzed using the Statistical Package for the Social Sciences (SPSS). Results The study sample included 597 parents, of which 339 (56.8%) were female and 258 (43.2%) were male. Our research demonstrated that 388 (65%) participants had an insufficient understanding of IMD, while 209 (35%) had a sufficient understanding. There was a significant correlation between the knowledge score and the completion of the routine vaccination and whether vaccinating a child is essential for the protection of other members of society. Conclusions Based on our study, only around one-third of the participants demonstrated a sufficient level of knowledge regarding IMD and its vaccination. To provide a more accurate assessment of the Saudi population, additional research should be conducted in various regions and cities.

This study analyzed hospital admissions for invasive meningococcal disease (IMD) in epidemiological and economic terms in Italy from 2015 to 2019. The volume of acute admissions for meningococcal diagnosis was analyzed in the period from 2015 to 2019. IMD admissions were identified by ICD-9-CM diagnoses. Costs were assessed using current DRG tariffs. In 2019, a total of 237 admissions for meningococcal disease were recorded in Italy. The mean age of patients was 36.1 years. Lumbar puncture was reported in only 14% of hospital discharge forms. From 2015 to 2019, there was a mean annual reduction of - 1.2% nationally for IMD hospitalizations. For 2019, the total costs for acute inpatient admissions were €2,001,093. Considering annual incidence due to IMD, a significant decrease was noted in the age group from 0 to 1 year (p = 0.010) during 2015-2019. For all years, mortality associated with meningeal syndrome was lower compared to septic shock with or without meningitis. From 2015 to 2019, hospitalizations for IMD appear to be decreasing slightly in Italy, even if mortality remains high. Favorable trends in hospitalizations for IMD were seen in the 0-1-year age group, which may be attributable to increased vaccination. Costs of hospitalizations for IMD remain high.

MenACYW-TT (MenQuadfi®) is a quadrivalent meningococcal tetanus toxoid conjugate vaccine licensed in Europe for use in individuals ≥12 months. This study assessed whether serogroup C immune responses with MenACYW-TT were at least non-inferior, or superior, to those of quadrivalent meningococcal ACWY (MCV4-TT; Nimenrix®) and monovalent meningococcal C (MenC-TT; NeisVac-C®) vaccines in toddlers (12-23 months). In this modified, double-blind Phase III study (NCT03890367), 701 toddlers received one dose of MenACYW-TT (n = 230), MCV4-TT (n = 232) or MenC-TT (n = 239). Serum bactericidal assays with human (hSBA) and baby rabbit (rSBA) complement were used to measure anti-meningococcal serogroup C antibodies at baseline and 30 days post-vaccination. A sequential statistical approach was used for primary and secondary objectives. For the primary objectives, superiority of serogroup C was assessed in terms of hSBA seroprotection rates (defined as titers ≥1:8) and GMTs for MenACYW-TT compared to MCV4-TT, and rSBA GMTs compared to MenC-TT. The safety of all vaccines within 30 days post-vaccination was described. When administered as a single dose to meningococcal vaccine-naïve healthy toddlers the superiority of the MenACYW-TT serogroup C immune response versus MCV4-TT was demonstrated for hSBA GMTs (ratio 16.3 [12.7-21.0]) and seroprotection (difference 10.43% [5.68-16.20]); and versus MenC-TT in terms of rSBA GMTs (ratio 1.32 [1.06-1.64]). The safety profiles of a single dose of MenACYW-TT, MCV4-TT and MenC-TT were similar. In meningococcal vaccine-naïve toddlers, MenACYW-TT induced superior immune responses to serogroup C versus MCV4-TT in terms of hSBA seroprotection and GMTs and versus MenC-TT in terms of rSBA GMTs.

BACKGROUND: The MenACYW-TT conjugate vaccine is approved for prevention of invasive meningococcal disease (IMD) as a single dose in individuals ≥2 years of age in the United States and ≥12 months in EU and some other countries. This Phase II study evaluated the safety and immunogenicity of this vaccine and of concomitant pediatric vaccines in infants/toddlers (6 weeks-15 months of age).
METHODS: Five schedules of the MenACYW-TT conjugate vaccine were evaluated in the United States: 2, 4, 6, and 12 months; 2, 4, 6, and 15 months; 2, 4, and 12 months; 6 and 12 months; and 12 months alone. Routine pediatric vaccines (DTaP-IPV/Hib, PCV7/PCV13, MMR, and varicella) were administered per approved schedules. Proportions of participants with serum bactericidal antibodyassay with human complement (hSBA) titers ≥1:4 and ≥1:8, SBA with baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128, and immune responses against concomitant vaccines were determined.
RESULTS: Tenderness and irritability were the most frequent solicited injection site and systemic reactions. Similar proportions of participants achieved an hSBA titer ≥1:8 for all four serogroups regardless of whether 2 or 3 doses were administered in the first year of life. Following a second-year dose, 91-100% of participants achieved the threshold for all 4 serogroups in all schedules regardless of the number of doses in the first year of life. Similar responses were seen with rSBA. Immunogenicity and safety profile of concomitant vaccines was similar whether the MenACYW-TT conjugate vaccine was administered or not.
CONCLUSIONS: MenACYW-TT conjugate vaccine administered with pediatric vaccines is safe and immunogenic regardless of the schedule and does not affect the immunogenicity or safety of the concomitant vaccines.
BACKGROUND: NCT01049035.

BACKGROUND: In response to the recent serogroup W invasive meningococcal disease (IMD-W) epidemic in the Netherlands, meningococcal serogroup C (MenC) conjugate vaccination for 14-month-olds was replaced with a MenACWY conjugate vaccination, and a mass campaign targeting 14-18 year-olds was executed. We investigated the impact of MenACWY vaccination implementation in 2018-2020 on incidence rates and estimated vaccine effectiveness (VE).
METHODS: We extracted all IMD cases diagnosed between July 2014 and December 2020 from the national surveillance system. We calculated age group-specific incidence rate ratios by comparing incidence rates before (July 2017-March 2018) and after (July 2019-March 2020) MenACWY vaccination implementation. We estimated VE in vaccine-eligible cases using the screening method.
RESULTS: Overall, IMD-W incidence rate lowered by 61% (95%CI 40-74). It declined by 82% (95%CI 18-96) in vaccine-eligible age group (15-36 month-olds and 14-18 year-olds) and by 57% (95%CI 34-72) in vaccine non-eligible age groups. VE was 92% (95%CI -20-99.5) against IMD-W vaccine-eligible toddlers. No IMD-W cases were reported in vaccine-eligible teenagers after the campaign.
CONCLUSIONS: The MenACWY vaccination programme was effective in preventing IMD-W in the target population. The IMD-W incidence reduction in vaccine non-eligible age groups may be caused by indirect effects of the vaccination programme. However, disentangling natural fluctuation from vaccine-effect was not possible. Our findings encourage the use of toddler- and teenager MenACWY vaccination in national immunization programmes especially when implemented together with a teenager mass campaign during an epidemic.

Surveillance of serogroup B Neisseria meningitidis (MenB) subcapsular antigen variant distribution in invasive disease (IMD) is fundamental for multicomponent vaccine coverage prediction. IMD incidence in Tuscany in 2018 was 0.37/100,000 inhabitants, with MenB representing 57% of cases. More than 50% of MenB responsible for IMD cannot be grown in culture, and molecular characterization of these cases is often lacking. The aim of the present study was to describe the distribution of MenB subcapsular antigens, comparing their distribution in culture-positive and culture-negative cases.
Molecular data regarding clonal complexes and subcapsular antigen variants of the 55 MenB-IMD occurring in Tuscany from 2007 to 2019 were made available, and their distribution between culture-positive and culture-negative cases was compared. Genetic-MATS and MenDeVAR prediction systems were used to assess multicomponent vaccine coverage predictions.
Culture-positive and culture-negative cases presented a similar percentage representation of fHbp subfamilies. Clonal complex 162 was almost constantly associated with fHbp B231/v1.390, Neisserial-heparin-binding-antigen (NHBA) peptide 20, and PorinA P1.22,14 (BAST-3033): these were the most represented antigenic variants, both in culture-positive and culture-negative groups. Point-estimate 4CMenB coverage prediction was 88.5% (84.6%-92.3%).
Our data demonstrate that non-cultivable meningococci, responsible for IMD, possess genetic variants of subcapsular antigens that are representative of what has been observed in culture. The vaccine-related antigenic epidemiology of MenB is thus similar in both groups. One of the first on-field applications of gMATS and MenDeVAR identifies their major advantage in their accessibility and in the possibility of dynamic data implementation that must be pursued continuously in the future.

BACKGROUND: An extensive clinical development program showed that the meningococcal serogroup B-factor H binding protein (MenB-FHbp) vaccine affords protection against MenB disease for adolescents and adults. Data were pooled from multiple studies within the program to examine whether MenB-FHbp immunogenicity was influenced by sex, age, or race.
METHODS: Immunogenicity was assessed in subjects from seven studies who received 120 µg MenB-FHbp (at 0, 2, 6 months) and had evaluated immune responses against four representative test strains via serum bactericidal assays using human complement (hSBAs). Immune responses were presented by sex (male, female), age group (10-14, 15-18, 19-25, 10-25 years), and race (white, black, Asian, other).
RESULTS: Among 8026 subjects aged 10-25 years included in this analysis, MenB-FHbp elicited robust immune responses in a high percentage of subjects regardless of demographic characteristics. Across all test strains and demographic subsets, a ≥ 4-fold rise in titer from baseline was achieved in 76.7-95.0% of subjects, with no major differences by sex, age groups assessed, or races evaluated. Corresponding percentages achieving titers ≥ the lower limit of quantification (LLOQ) against all four strains combined were 79.7-87.3% (sex), 81.6-85.5% (age), and 80.0-88.1% (race). Minor differences were observed for geometric mean titers and percentages of subjects achieving titers ≥ LLOQ against each strain based on demographics.
CONCLUSIONS: These data suggested no clinically meaningful differences in MenB-FHbp immunogenicity when administered as a three-dose schedule based on sex, ages assessed, or races evaluated. This analysis supports the continued recommended use of MenB-FHbp to prevent MenB disease in adolescents and young adults.
BACKGROUND: ClinicalTrials.gov identifiers, NCT00808028, NCT01830855, NCT01323270, NCT01461993, NCT01461980, NCT01352845, and NCT01299480.

MenACYW-TT is an investigational quadrivalent (serogroups A, C, W and Y) meningococcal conjugate vaccine that is being developed for protection against invasive meningococcal disease.
In this Phase 3, blinded, randomized study, 3344 meningococcal vaccine-naïve 10-55-year-olds were randomized (3:3:3:2) to receive one of three lots of MenACYW-TT or licensed quadrivalent meningococcal conjugate vaccine, MCV4-DT (NCT02842853). Antibody titers were assessed by human and rabbit complement serum bactericidal antibody assays. The co-primary objectives were to demonstrate lot-to-lot consistency of MenACYW-TT by the between-lot geometric mean titer ratios (GMTR) at Day 30, and non-inferiority of Day 30 vaccine seroresponses (titers ≥ 1:16 if pre-vaccination titers < 1:8, or ≥ 4-fold increase if pre-vaccination titers ≥ 1:8) with MenACYW-TT vs MCV4-DT. Further objectives included safety and immunogenicity.
Lot consistency was demonstrated for all three lots, with GMTRs ranging from 0.87 to 1.1. The proportion of participants achieving seroresponse in the MenACYW-TT group (data pooled from the 3 lots) was non-inferior to MCV4-DT (A: 74% vs 55%; C: 89% vs 48%; W: 80% vs 61%; Y: 91% vs 73%, respectively). MenACYW-TT and MCV4-DT had similar safety profiles; no safety concerns were identified.
The study met both co-primary endpoints, demonstrating lot-to-lot consistency and non-inferiority of MenACYW-TT vs MCV4-DT in adolescents and adults.

Background University students are at particular risk of invasive meningococcal disease (IMD). Group W, an aggressive strain, is increasing in prevalence and the high case-fatality rate is concerning. Adolescents have been offered the MenACWY vaccine since 2015. National uptake has been low, leaving students vulnerable to infection. Objectives To investigate MenACWY uptake, knowledge of IMD and attitudes towards vaccination among UCL first-year students. Methods A mixed methods approach was used, involving a questionnaire (n=144) and follow-up interviews (n=13). Students were asked for demographic details and questions including vaccination status, awareness of the vaccine, other vaccination history and knowledge of IMD, which was assessed through true/false/unsure statements. Interviews explored these issues in more detail as well as their suggestions for making vaccination more accessible for students. Results MenACWY uptake was 84%, with more socioeconomically disadvantaged students being less likely to be vaccinated (aOR=0.117, p=0.006). Most students thought vaccines were safe and important. Students with above average knowledge were more likely to be vaccinated (OR=3.057, p=0.019). Vaccination views were positive and knowledge level was moderate to high. Reasons for non-vaccination included illness, laziness, forgetfulness and difficulty with GP access. Of concern, many students believed that the vaccine prevents any cause of meningitis. Conclusion High vaccine uptake is essential to protect students. Uptake at University College London is higher than at other universities in previous studies. This research highlights several areas requiring further study and has implications for university vaccination policy.