MenB Vaccine Research Articles

Integrated Genomic Surveillance of Invasive Meningococcal Disease in Scotland 2015-2022, Following the Introduction of Routine Infant MenB Vaccination

Integrated Genomic Surveillance of Invasive Meningococcal Disease in Scotland 2015-2022, Following the Introduction of Routine Infant MenB Vaccination

A questionnaire-based study to assess knowledge and attitudes to meningococcal disease and prevention among parents of children up to two years in Lithuania.

In July 2018, vaccine against meningococcal B infection in Lithuania was added to the national vaccination calendar. However, vaccination rates were low. The aim of the study was to identify parents' attitudes towards meningococcal disease and vaccination. In the period from February to March 2019, a questionnaire survey was conducted; 483 parents of children aged up to 2 years participated. In the validated questionnaire respondents provided data on their gender, education, age and answered questions that helped to estimate knowledge and attitudes towards meningococcal disease and vaccination. Parents with higher education are more likely to believe that meningococcal infection can be prevented; 316 (65.4%) parents are concerned that their child is at high risk of infection and evaluated the level of anxiety M = 7.39, SD = 2.29 out of 10 points; 309 (64.0%) believe that the vaccine is effective (M = 8.41; SD = 1.15 out of 10 points). One third of parents will not vaccinate their children because they believe that the MenB vaccine is not safe (71.2%); 370 (76.6%) have heard negative information about this vaccine, the majority (83.2%) from the Internet. The negative information received is positively correlated with the belief that the vaccine is not effective (r = 0.18, p = 0.031) and not safe (r = 0.35, p < 0.001); 49.3% of parents report side effects after vaccination; 326 (67.5%) parents believe that they need more evidence-based information on MenB vaccination and 90.8% would like to get it from a healthcare professional. Due to high level of mistrust of vaccines and the lack of evidence-based information, parents decide not to vaccinate their children against meningococcal B infection. There is a great need for parents' education and the dissemination of evidence-based information among them.

Public Health Impact and Cost-Effectiveness Analysis of Routine Infant 4CMenB Vaccination in Germany to Prevent SerogroupB Invasive Meningococcal Disease.

IntroductionInvasive meningococcal disease (IMD) is an uncommon, severe, life-threatening disease primarily affecting infants, with potential lifelong sequelae. Neisseria meningitidis (Nm) serogroup B (MenB) causes most IMD cases in Germany, many of which can be prevented with four-component MenB (4CMenB) vaccination. The potential public health and economic impact of introducing routine 4CMenB infant vaccination in Germany was assessed.MethodsA dynamic transmission-based cost-effectiveness model adapted for Germany assessed the impact of infant 4CMenB universal mass vaccination (UMV) versus no vaccination. The model included the latest real-world evidence on vaccine effectiveness, the comprehensive burden of disease on patients (sequelae) and their family (quality of life impact), comprehensive German IMD costs, and vaccination uptake assumptions.ResultsThe largest public health impact was predicted in children: a rapid decline, 5 years after UMV implementation, of 39.9% (34.7%) for MenB (all IMD) cases aged 0–4 years and 42.4% (36.8%) in infants. Over lifetime (100-year time horizon), 4CMenB could prevent 3154 MenB (3303 all IMD) cases, 291 MenB (304 all IMD) deaths and 1370 MenB (1435 all IMD) long-term sequelae. 4CMenB saved 25,878 quality-adjusted life-years (QALYs), at a cost of €188,762 per QALY gained in the base case (societal perspective including lost productivity). Scenarios including potential Nm carriage protection (enabling herd protection) or societal preferences for the prevention of severe diseases led to more cost-effective results, while a scenario excluding IMD impact beyond the patient with increased discounting of vaccination health benefits produced less cost-effective results.ConclusionsMenB IMD is a vaccine-preventable disease. This analysis for Germany can inform decision-makers on the potential impact of introducing infant 4CMenB UMV. The program is predicted to rapidly produce health benefits (reduction in child cases, deaths and sequelae) at a cost per QALY to society of around €190,000 (base case), decreasing to around €78,000 when considering societal preferences and IMD underreporting.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00573-w.

01. Serum Bactericidal Activity Against Circulating and Reference Strains of Meningococcal Serogroup B in the United States: A Review of Meningococcal Serogroup B (MenB) Vaccines in Adolescents and Young Adults

BackgroundUS adolescents and young adults are at particular risk of invasive meningococcal disease (IMD). In 2018, menincococcal serogroup B was responsible for 36% of IMD cases in the US overall and for 66% of cases in adolescents and young adults. This age group is at high risk of IMD during outbreaks, which result in significant response-related costs. MenB vaccine efficacy against IMD relies on its ability to provide broad protection against diverse disease-causing strains. MenB-FHbp (Trumenba) and MenB-4C (Bexsero) are MenB vaccines licensed in the US as 2-dose series with an interval of 6 mo or 1 mo, respectively, recommended in healthy adolescents and young adults. We review available data on vaccine coverage of serogroup B strains.MethodsA literature review identified relevant information from peer-reviewed publications, congress presentations, and ClinicalTrials.gov. Previously presented but unpublished data from phase 2/3 studies were included.ResultsAfter 2 MenB-FHbp doses, percentages of adolescents and young adults achieving serum bactericidal activity assay using human complement (hSBA) titers ≥1:8 were 79%–99% for 4 heterologous representative test strains and 71%–97% for 10 additional strains, confirming cross-protection against a diverse strain panel (Figure 1; unpublished data). These 14 heterologous strains collectively represent ~80% of disease-causing strains in the US and Europe. In a published study with limited sample size, 44%–78% of subjects had hSBA titers ≥1:8 against strains from 4 US college outbreaks after 2 MenB-FHbp doses. After 2 MenB-4C doses, percentages of 10–25-year-olds achieving hSBA titers ≥1:5 against 3 reference strains homologous to the vaccine antigen were 82%–93% (published data); 15%–100% of adolescents achieved hSBA titers ≥1:4 against a panel of 14 strains (unpublished data). Of college students who received 2 MenB-4C doses, 53%–93% achieved hSBA titers ≥1:4 against 5 US outbreak strains (4/5 strains had antigenic similarity to MenB-4C; published data). ConclusionMenB-FHbp and MenB-4C protect against various serogroup B strains. As for the breadth of coverage provided by these vaccines, available data show that MenB-FHbp elicits robust immune responses to a wide variety of disease-causing strains prevalent in the US (Figure 2). Disclosures Tamera Coyne-Beasley, MD, MPH, Pfizer Inc and GlaxoSmithKline (Advisor or Review Panel member) Joseph Bocchini, MD, Pfizer Inc and Dynavax (Advisor or Review Panel member) Alejandro Cane, M.D., Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Maria J. Tort, PhD, Pfizer Inc (Employee, Shareholder) Jessica Presa, MD, Pfizer Inc (Employee, Shareholder)

03. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered as a Booster Dose in Adults and Adolescents Vaccinated Against Meningococcal Disease 3 - 6 Years Earlier

BackgroundBooster doses of meningococcal conjugate vaccines may induce long-term protection against invasive meningococcal disease. MenACYW-TT [MenQuadfi®] is a quadrivalent meningococcal conjugate vaccine, licensed for use in ages 2 years and older in USA. The vaccine is also licensed in ages 12 months and older in EU and other countries.MethodsA phase IIIb study (NCT04084769) was conducted to evaluate the persistence of immune response in adults and adolescents primed 3-6 years earlier with either MenACYW-TT or MCV4-CRM (Menveo®) and, safety and immunogenicity of MenACYW-TT when administered as a booster dose with or without concomitant administration with MenB vaccines (Bexsero® and Trumenba®). Serum bactericidal assays with human complement (hSBA) and baby rabbit complement (rSBA) were used to measure antibodies against vaccine serogroups at baseline (Day 0 [D0]), D06 (in a subset) and 30 days post-vaccination (D30). Safety data were collected up to 6 months post-vaccination.ResultsAt D0, the GMTs were higher in subjects primed with MenACYW-TT vs MCV4-CRM for serogroups C, Y and W, and were comparable for serogroup A. At D0, all hSBA GMTs were higher than those observed pre-priming dose, suggesting persistence of immunity. Sufficiency of hSBA seroresponse ( >75%) was demonstrated following administration of MenACYW-TT booster dose regardless of the priming vaccine administered 3-6 years earlier. Vaccine seroresponse in a subset of participants at D06 ranged from 77.8% (95%CI 62.9%; 88.8%) for serogroup A to 97.8% (88.5%; 99.9%) for serogroup W suggesting a quick onset of immune response post-booster. Post-vaccination (D30) hSBA GMTs were comparable for serogroups A, Y and W regardless of the nature of the priming vaccine and were higher for serogroup C in subjects primed with MenACYW-TT vaccine. The MenACYW-TT booster dose was well-tolerated and had similar safety profiles regardless of the priming vaccine. The safety profiles were comparable regardless of the MenB vaccine co-administered with MenACYW-TT vaccine.ConclusionMenACYW-TT used as priming vaccine was able to demonstrate persistence of immune response 3-6 years later. MenACYW-TT elicits robust booster responses in adults and adolescents primed with MenACYW-TT or MCV4-CRMDisclosures Betzana Zambrano, MD, Sanofi Pasteur (Employee) Germán Áñez, MD, Sanofi Pasteur (Other Financial or Material Support, Former employee) Sue Jiayuan, MSc, Sanofi Pasteur (Independent Contractor) Judy Pan, PhD, Sanofi Pasteur (Employee) Habiba Arroum, MD, Sanofi Pasteur (Employee) Kucku Varghese, PhD, Sanofi Pasteur (Employee) Emilia Jordanov, MD, Sanofi Pasteur (Employee, Shareholder) Mandeep S. Dhingra, MD, Sanofi Pasteur (Employee, Shareholder)

Modeling the public health impact of different meningococcal vaccination strategies with 4CMenB and MenACWY versus the current toddler MenACWY National Immunization Program in Chile

ABSTRACT Invasive meningococcal disease (IMD) is an uncommon yet unpredictable, severe, and life-threatening disease with the highest burden in young children. In Chile, most IMD is caused by meningococcal serogroup B (MenB) and W (MenW) infection. In response to a MenW outbreak in 2012, a toddler vaccination program was implemented using quadrivalent meningococcal conjugate vaccine against serogroups A, C, W and Y (MenACWY). The vaccine program, however, does not protect infants or other unvaccinated age groups and does not protect against MenB IMD. Since 2017, MenB IMD cases are becoming increasingly prevalent. Using a dynamic transmission model adapted for Chile, this analysis assessed the public health impact (reduction in IMD cases, long-term sequelae, deaths, and quality-adjusted life-years) of six alternative vaccination strategies using MenACWY and/or the four-component MenB (4CMenB) vaccine in infants, toddlers, and/or adolescents compared to the National Immunization Program (NIP) implemented in 2014. Strategies that added infant 4CMenB to MenACWY in toddlers or adolescents would prevent more IMD than the current NIP, observed within the first 5 years of the program. Replacing the NIP by an adolescent MenACWY strategy would prevent more IMD in the longer term, once herd immunity is established to protect unvaccinated infants or older age groups. The strategy that maximized reduction of IMD cases and associated sequelae in all age groups with immediate plus long-term benefits included infant 4CMenB and MenACWY in both toddlers and adolescents. This analysis can help policymakers determine the best strategy to control IMD in Chile and improve public health. A set of audio slides linked to this manuscript can be found at https://doi.org/10.6084/m9.figshare.16837543.

Invasive serogroup B meningococci in England following three years of 4CMenB vaccination – First real-world data

ObjectivesIn 2015 the UK became the first country to implement the meningococcal B (MenB) vaccine, 4CMenB, into the national infant program. 4CMenB is expected to cover meningococci expressing sufficient levels of cross-reactive proteins. This study presents clonal complex, 4CMenB antigen genotyping, and 4CMenB coverage data for all English invasive MenB isolates from 2014/15 (1 year pre-vaccine) through 2017/18 and compares data from vaccinated and unvaccinated ≤3 year olds. MethodsVaccine coverage of all invasive MenB isolates from 2014/15 to 2017/18 (n = 784) was analysed using the Meningococcal Antigen Typing System. Genotyping utilised the Meningococcus Genome Library. ResultsAmong ≤3 year olds, proportionally fewer cases in vaccinees (1, 2 or 3 doses) were associated with well-covered strains e.g. cc41/44 (20.5% versus 36.4%; P<0.01) and antigens e.g. PorA P1.4 (7.2% versus 17.3%; P = 0.02) or fHbp variant 1 peptides (44.6% vs 69.1%; P<0.01). Conversely, proportionally more cases in vaccinees were associated with poorly-covered strains e.g. cc213 (22.9% versus 9.6%; P<0.01) and antigens e.g. variant 2 or 3 fHbp peptides (54.2% versus 30.9%; P<0.01). Conclusions4CMenB reduces disease due to strains with cross-reactive antigen variants. No increase in absolute numbers of cases due to poorly covered strains was observed in the study period.

Serogroup B meningococcal disease in persons previously vaccinated with a serogroup B meningococcal vaccine – United States, 2014–2019

Since serogroup B meningococcal (MenB) vaccines became available in the United States, six serogroup B meningococcal disease cases have been reported in MenB-4C (n = 4) or MenB-FHbp (n = 2) recipients. Cases were identified and characterized through surveillance and health record review. All five available isolates were characterized using whole genome sequencing; four isolates (from MenB-4C recipients) were further characterized using flow cytometry, MenB-4C-induced serum bactericidal activity (SBA), and genetic Meningococcal Antigen Typing System (gMATS). Three patients were at increased meningococcal disease risk because of an outbreak or underlying medical conditions, and only four of the six patients had completed a full 2-dose MenB series. Isolates were available from 5 patients, and all contained sub-family A FHbp. The four isolates from MenB-4C recipients expressed NhbA but were mismatched for the other MenB-4C vaccine antigens. These four isolates were relatively resistant to MenB-4C-induced SBA, but predicted by gMATS to be covered. Overall, patient risk factors, incomplete vaccine series completion, waning immunity, and strain resistance to SBA likely contributed to disease in these six patients.

Low Meningococcal Vaccination Rates Among Patients With Newly Diagnosed Complement Component Deficiencies in the United States.

Meningococcal vaccination is recommended for patients with complement component deficiencies (CDs) in the United States. In this retrospective database study, only 4.6% and 2.2% of patients received MenACWY and MenB vaccination, respectively, within 3 years of CD diagnosis. Thus, meningococcal vaccination rates among patients with CDs need to be improved.

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

BackgroundMeningococcal 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.MethodsMenACWY 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.ResultsAt 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).ConclusionsThere was a statistically significant improvement in MenACWY but not MenB vaccination rates, indicating a need for more effective measures in addressing low MenB coverage.

Factors Associated With Receipt of Meningococcal B Vaccine Among United States Adolescents, National Immunization Survey-Teen, 2017–2018

PurposeIn this study, we evaluated factors associated with receipt of meningococcal serogroup B (MenB) vaccine among adolescents in the United States. MethodsWe used public use data files from the National Immunization Survey-Teen from 2017 to 2018. Logistic regression was used to model associations among sociodemographic, healthcare, and vaccination variables of interest and MenB vaccine receipt (≥1 vs. 0 dose). To explore associations between state-level meningococcal vaccination requirements and MenB vaccine uptake, we performed a secondary analysis stratified by presence of a quadrivalent meningococcal (MenACWY) vaccination requirement for secondary school attendance in the adolescent’s state of residence (no requirement vs. a one- or two-dose requirement). ResultsAmong 7,288 adolescents, MenB vaccine receipt was significantly associated with up-to-date human papillomavirus (adjusted odds ratio [aOR] 1.74, 95% confidence interval [CI] 1.29–2.35) and MenACWY (aOR 5.81, 95% CI 4.14–8.13) vaccination status in multivariable analysis. Adolescents with private insurance were less likely to be vaccinated (aOR .61, 95% CI .46–.79) compared to adolescents with other health insurance types. In secondary analyses, health insurance was no longer significantly associated with MenB vaccine uptake among adolescents in states with a MenACWY requirement. ConclusionsWe found that MenB vaccination is associated with receipt of other vaccines recommended for use in adolescents. Adolescents with private health insurance were less likely to be vaccinated against MenB, although state MenACWY requirements appeared to modify the effect of insurance on MenB vaccine receipt. Further work to understand how these factors may influence delivery and acceptance of MenB vaccine can inform interventions and strategies to improve uptake.

A Laboratory-Based Surveillance Study of Invasive Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae Diseases in a Serbian Pediatric Population-Implications for Vaccination.

The aim of this study was to present the epidemiology of invasive diseases caused by Neisseria meningitidis and Streptococcus pneumoniae in the pre-vaccine period, and Haemophilus influenzae in the post-vaccine period in a pediatric population from Serbia. Among the meningococci, serogroup B dominated (83%), followed by serogroup C (11.3%). High antigenic diversity was found, with fine type P1.5-1,10-4 being the most frequent. Moderate susceptibility to penicillin was common (55%). Within pneumococci, serotypes 19F, 14, 6B, 6A, 18C, 23F, 3, and 7F prevailed, while 19A was rare (3.6%). The coverages of PCV10 and PCV13 were 68% and 84%, respectively. Major sequence types were ST320, ST15, ST273, ST271, and ST81. Non-susceptibility to penicillin (66.7%), cefotaxime (37%), and macrolides (55%) was predominantly detected in vaccine-related serotypes. Among the 11 invasive H. influenzae isolates collected, there were six Hib, three non-type b, and two non-typeable strains (ntHi) that were antibiotic susceptible. These results imply a potential benefit of future Men-B vaccine implementations. For pneumococci, as PCV10 was recently introduced, a significant reduction of morbidity and antibiotic resistance might be expected. The efficiency of Hib vaccination is evident, but a shift towards non-type b and ntHi strains may be anticipated.

Increasing awareness and uptake of the MenB vaccine on a large university campus

ABSTRACT Objective: At a large public university, we aimed to evaluate an intervention designed to increase serogroup B meningococcal (MenB) vaccine uptake and awareness. Methods: Using a pretest-posttest design with a double posttest, we evaluated an intervention conducted by a local foundation and the Florida Department of Health that distributed MenB vaccine on campus and conducted an educational campaign. Prior to intervention activities, we recruited students to complete a survey about their MenB knowledge and attitudes. For survey participants who provided contact information, we sent two follow-up surveys and assessed MenB vaccine records. We used chi-square tests, adjusted for nonindependence, to compare preintervention to postintervention (three-month and one-year) vaccination and attitudes. Results: Among the 686 students with accessible vaccine records, MenB vaccine initiation increased 9% (from 24% to 33%) and completion increased 8% (from 13% to 21%) from before the intervention to one year after the intervention. When restricting to students who completed the relevant follow-up surveys, the percentage of students who heard of the MenB vaccine increased by 15% (p > .001) from before the intervention to three months after (n = 188 students) and maintained a 10% increase (p > .001) one year after the intervention (n = 261 students). Among students that heard of the MenB vaccine, the percentage of students who thought they needed the MenB vaccine even though they received the MenACWY increased 14% (p = .03) by the three-month postintervention survey and up to 18% by the one-year follow-up (p = .002). Conclusions: A university-wide, on-campus vaccination and educational campaign increased college students’ MenB vaccine initiation, completion, and knowledge. Clinicaltrials.gov ID: NCT02975596.

Cumulative annual coverage of meningococcal B vaccination in Australian general practice for three at-risk groups, 2014 to 2019

ABSTRACT Neisseria meningitidis serogroup B (MenB) is the most common cause of meningococcal disease in adolescents and young adults. In Australia, MenB vaccination has been available through private prescription since 2014 and has been recommended for at-risk groups including adolescents, young adults who smoke and people medically at risk. For each of these at-risk groups, we estimated cumulative annual coverage of MenB vaccination between 2014 and 2019. We also evaluated factors associated with vaccination coverage in 2019. Our analyses used electronic health records in the national MedicineInsight database for people regularly attending general practices. Cumulative vaccination coverage increased among the at-risk groups between 2014 and 2019: from 0.09% to 1.65% for adolescents, from 0.01% to 0.15% for young adults who smoke, and from 0.35% to 12.09% for people medically at risk. However, vaccination coverage in 2019 remained very low across these groups. Data sparsity prevented the evaluation of factors associated with vaccination coverage for smokers. We observed variation in the relative risk of being vaccinated by age, sex, socioeconomic and clinical factors for adolescents and people medically at risk. Still, the absolute magnitude of coverage was low across all subgroups examined, and indicates a need for strategies to increase vaccination uptake among at-risk groups irrespective of patient and practice characteristics. Our study provides baseline data for monitoring menB vaccination uptake among recommended groups in light of limited national data, especially for medically at-risk groups.

Genetic Diversity of Meningococcal Serogroup B Vaccine Antigens among Carriage Isolates Collected from Students at Three Universities in the United States, 2015-2016.

ABSTRACTCarriage evaluations were conducted during 2015 to 2016 at two U.S. universities in conjunction with the response to disease outbreaks caused by Neisseria meningitidis serogroup B and at a university where outbreak and response activities had not occurred. All eligible students at the two universities received the serogroup B meningococcal factor H binding protein vaccine (MenB-FHbp); 5.2% of students (181/3,509) at one university received MenB-4C. A total of 1,514 meningococcal carriage isolates were obtained from 8,905 oropharyngeal swabs from 7,001 unique participants. Whole-genome sequencing data were analyzed to understand MenB-FHbp’s impact on carriage and antigen genetic diversity and distribution. Of 1,422 isolates from carriers with known vaccination status (726 [51.0%] from MenB-FHbp-vaccinated, 42 [3.0%] from MenB-4C-vaccinated, and 654 [46.0%] from unvaccinated participants), 1,406 (98.9%) had intact fHbp alleles (716 from MenB-FHbp-vaccinated participants). Of 726 isolates from MenB-FHbp-vaccinated participants, 250 (34.4%) harbored FHbp peptides that may be covered by MenB-FHbp. Genogroup B was detected in 122/1,422 (8.6%) and 112/1,422 (7.9%) isolates from MenB-FHbp-vaccinated and unvaccinated participants, respectively. FHbp subfamily and peptide distributions between MenB-FHbp-vaccinated and unvaccinated participants were not statistically different. Eighteen of 161 MenB-FHbp-vaccinated repeat carriers (11.2%) acquired a new strain containing one or more new vaccine antigen peptides during multiple rounds of sample collection, which was not statistically different (P = 0.3176) from the unvaccinated repeat carriers (1/30; 3.3%). Our findings suggest that lack of MenB vaccine impact on carriage was not due to missing the intact fHbp gene; MenB-FHbp did not affect antigen genetic diversity and distribution during the study period.

Meningococcal B vaccination coverage among older adolescents in the United States

BackgroundSerogroup B meningococcal (MenB) vaccination recommendations for adolescents in the United States (US) include routine vaccination for all individuals at increased risk and vaccination for individuals not at increased risk aged 16–23 years (preferred age 16–18 years) based on shared clinical decision-making. The two licensed MenB vaccines require administration of ≥2 doses. MethodsThis cross-sectional study analyzed 2017–2018 National Immunization Survey-Teen (NIS-Teen) data to evaluate ≥1 dose and ≥2 dose MenB vaccination coverage among adolescents aged 17 years. Multivariable logistic regression was used to further evaluate determinants of MenB vaccination. ResultsNationally, MenB vaccination coverage among 17-year-olds increased from 14.5% in 2017 to 17.2% in 2018 for ≥1 dose and from 6.3% to 8.4% for ≥2 doses. MenB vaccination coverage (2017–2018) was the lowest in the South (≥1 dose: 14.6%; ≥2 doses: 6.3%) and highest in the Northeast region (18.3% and 9.3%), with variation observed by census division. Adolescents were more likely to have received ≥1 dose of MenB vaccine if they had any Medicaid insurance (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.32–2.39) or had received human papillomavirus (OR, 1.94; 95% CI, 1.41–2.67) or meningococcal A, C, W, and Y (OR, 4.03; 95% CI, 2.92–5.56) vaccinations. ConclusionsMenB first-dose coverage in the US is low, and even lower for a second dose, with regional variation. Being up to date with other routinely administered vaccines increased the likelihood of receiving MenB vaccination.

Potential public health impact of a Neisseria meningitidis A, B, C, W, and Y pentavalent vaccine in the United States

ABSTRACT Objective Globally, 5 serogroups (A, B, C, W, and Y) cause the majority of invasive meningococcal disease (IMD). Vaccines targeting these serogroups are currently part of the US adolescent immunization platform, which includes 1 + 1 dosing of a MenACWY vaccine routinely at ages 11 and 16 years and 2 doses of a MenB vaccine at age 16–23 years under shared clinical decision-making between the patient and healthcare provider. In 2018, MenACWY vaccination coverage was 86.6% for ≥1 dose and 50.8% for ≥2 doses, whereas MenB vaccination coverage was 17.2% for ≥1 dose and <50% for completion of the multidose series. A pentavalent MenABCWY vaccine could simplify immunization schedules and improve vaccination coverage. We estimated the public health impact of a pentavalent MenABCWY vaccine using a model that considers meningococcal carriage and vaccination coverage. Methods A population-based dynamic model estimated the 10-year reduction in IMD from implementing a MenABCWY vaccine within the existing US meningococcal immunization platform. Five vaccination schedules (4 new, 1 existing) were examined to estimate the impact of different recommendations on the overall reduction in the number of IMD cases. Sensitivity analyses were performed by varying vaccination coverage at age 16 years. Results The existing schedule and coverage of MenACWY and MenB vaccines (total 4 doses) could potentially avert 165 IMD cases over 10 years versus no vaccination. Assuming similar MenABCWY and MenACWY vaccination coverage rates at age 16 years, replacing 1 or more MenACWY and/or MenB doses with MenABCWY could avert more cases, ranging from 189 to 256. The most beneficial MenABCWY vaccine schedule was 2 doses at age 11 years and 1 dose at age 16 years. Conclusions Replacing one or more MenACWY/MenB vaccine doses with MenABCWY could reduce IMD caused by all 5 meningococcal serogroups among the US adolescent population, while also reducing the number of injections required.

Molecular characterization of invasive serogroup B Neisseria meningitidis isolates from Spain during 2015–2018: Evolution of the vaccine antigen factor H binding protein (FHbp)

108, 103, 87 and 112 invasive MenB strains isolated during 2015-2018, respectively, were received at NRL. The strains were whole genome sequenced, and porA, fetA, MLST and fHbp variability was analyzed. Potential impact on MenB vaccines coverage was also assessed. A total of 42, 38 and 3 different FHbp subfamily A, B and A/B hybrid peptides, respectively, were found. FHbp subfamily A peptides were harboured by most of the strains (65.9%), being the most prevalent peptide 45 which was associated with genosubtype 22,14 and cc213. FHbp subfamily B peptides were harboured by 32.4% of the strains, and 6 strains harbouring subfamily A/B hybrid peptides were also found. The 64.15% of the strains showed FHbp variants "exact-match" or "cross-reactive" to the FHbp variants included in rLP2086 vaccine according to hSBA assays in the rLP2086 clinical development, and 15.85% showed FHbp peptides defined as predictors of FHbp-coverage for 4CMenB vaccine by gMATS. Due to invasive meningococcal strains temporal variability (eg prevalence of the cc213 increased from 3.6% in 2007 to 33% in 2018) affecting to the presence and distribution of the vaccine antigens, continuous detailed meningococcal surveillance and monitoring of the vaccine antigens is needed to determine the degree and durability of coverage provided by these protein vaccine.

Estimated strain coverage of serogroup B meningococcal vaccines: A retrospective study for disease and carrier strains in Greece (2010–2017)

Invasive meningococcal disease (IMD) is associated with high case fatality rates and long-term sequelae among survivors. Meningococci belonging to six serogroups (A, B, C, W, X, and Y) cause nearly all IMD worldwide, with serogroup B meningococci (MenB) the predominant cause in many European countries, including Greece (~80% of all IMD). In the absence of protein-conjugate polysaccharide MenB vaccines, two protein-based vaccines are available to prevent MenB IMD in Greece: 4CMenB (Bexsero™, GlaxoSmithKline), available since 2014; and MenB-FHbp, (Trumenba™, Pfizer), since 2018. This study investigated the potential coverage of MenB vaccines in Greece using 107 MenB specimens, collected from 2010 to 2017 (66 IMD isolates and 41 clinical samples identified solely by non-culture PCR), alongside 6 MenB isolates from a carriage study conducted during 2017–2018. All isolates were characterized by multilocus sequence typing (MLST), PorA, and FetA antigen typing. Whole Genome Sequencing (WGS) was performed on 66 isolates to define the sequences of vaccine components factor H-binding protein (fHbp), Neisserial Heparin Binding Antigen (NHBA), and Neisseria adhesin A (NadA). The expression of fHbp was investigated with flow cytometric meningococcal antigen surface expression (MEASURE) assay. The fHbp gene was present in-frame in all isolates tested by WGS and in 41 MenB clinical samples. All three variant families of fHbp peptides were present, with subfamily B peptides (variant 1) occurring in 69.2% and subfamily A in 30.8% of the samples respectively. Sixty three of 66 (95.5%) MenB isolates expressed sufficient fHbp to be susceptible to bactericidal killing by MenB-fHbp induced antibodies, highlighting its potential to protect against most IMD in Greece.

Implementation Experience With Meningococcal Serogroup B Vaccines in the United States: Impact of a Nonroutine Recommendation.

Meningococcal serogroup B (MenB) is the leading cause of invasive meningococcal disease among US adolescents and young adults, accounting for 62% of cases in 16-23-year-olds in 2018. Since 2015, the Advisory Committee on Immunization Practices (ACIP) has recommended vaccination of healthy adolescents against MenB based on shared clinical decision-making (previously called "Category B" or individual clinical decision-making). However, MenB vaccine coverage and series completion rates remain low. Herein we examine implementation experience of adolescent MenB vaccination in the United States under this nonroutine ACIP recommendation. PubMed was searched for English-language articles published after 2015 examining MenB vaccination implementation in the United States. Studies reporting MenB vaccination awareness, coverage, knowledge of recommendations and implementation barriers or access disparities were included. Identified studies provided evidence that ACIP's MenB vaccination recommendation is poorly understood and prone to misinterpretation by US healthcare providers. Parental awareness of MenB vaccines is low, and racial and socioeconomic disparities exist regarding vaccine receipt. Parents rely on providers to learn about MenB disease risk and benefits of vaccination, with provider recommendations carrying substantial weight in vaccination decisions. Five years of evidence regarding the MenB vaccination implementation experience suggest that the nonstandard recommendation for MenB vaccines is partly responsible for low vaccine coverage. Further, inconsistent implementation of ACIP recommendations could be limiting access to MenB vaccines. Providers need additional support and guidance to implement the shared clinical decision-making recommendation, in turn ensuring equitable access for vaccine-eligible adolescents to enable comprehensive protection against meningococcal disease.