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Background: Percentage uptake of some meningococcal vaccines is low in the US. Understanding what drives vaccination preferences may help to increase vaccination rates., Objectives: To determine how attributes of meningococcal vaccines and the availability of a pentavalent (MenABCWY) vaccine profile drive adolescents' and young people's (AYP's) willingness to be vaccinated and parents' and legal guardians' (PLG') willingness for their child to be vaccinated (WTV). To also explore how preferences for meningococcal vaccines vary by participant characteristics., Methods: Vaccine preferences were elicited in a discrete choice experiment (DCE) with AYP aged 16-23 years and PLG of adolescents aged 11-17 years. Participants chose between two hypothetical vaccine profiles that differed in level of protection, dosing, and risks of mild-to-moderate and severe side effects, and a no vaccination profile. Main outcome measures were relative attribute importance (RAI) and WTV. RAI measured the maximum contribution of an attribute to vaccination choice relative to other attributes. WTV compared predicted choice probabilities for the three vaccine profiles., Results: 407 AYP and 394 PLG participated (50.9% male, 78.4% White/Caucasian). Irrespective of vaccine attributes, 59.5% always opted into vaccination and 3.6% always opted out of vaccination. The most important attributes were level of protection (RAI: 33.7%) and risk of mild-to-moderate side effects (RAI: 32.3%). Dosing was more important to PLG (RAI: 5.9%) than AYP (RAI: 2.0%; p < .01). Adding a pentavalent vaccine alternative increased WTV by 3.7 percentage points (PP) for PLG, 2.4 PP for AYP, 16.4 PP for vaccine-hesitant participants, 13.4 PP for participants without health insurance, and 9.6 PP for adults., Conclusion: Level of protection and risk of mild-to-moderate side effects were the most important vaccine attributes. Adding a pentavalent vaccine alternative increased WTV particularly among adults, individuals who were vaccine-hesitant, and individuals without health insurance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katharina Schley reports a relationship with Pfizer Pharma GmbH that includes: employment. Brett Hauber reports a relationship with Pfizer Inc. that includes: employment. Joseph C. Cappelleri reports a relationship with Pfizer Inc. that includes: employment. Paula Peyrani reports a relationship with Pfizer Inc. that includes: employment. Jessica Vespa Presa reports a relationship with Pfizer Inc. that includes: employment. Joshua Coulter reports a relationship with Pfizer Inc. that includes: employment. Chiara Whichello reports a relationship with Evidera Ltd. that includes: employment. Nicolas Krucien reports a relationship with Evidera Ltd. that includes: employment. Sebastian Heidenreich reports a relationship with Evidera Ltd. that includes: employment. The following co-authors are employees of Pfizer and may hold stocks in Pfizer: KS, BH, JC, JCC, PP, and JVP. The following co-authors are employees of Evidera Ltd.: CW, SH, and NK. SH holds minor stocks in Thermo Fisher Scientific as part of his employment with Evidera. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Meningococcal disease is caused by Neisseria meningitidis or meningococcus. Every year globally around 1.2 million people are affected and approximately 120,000 deaths occur due to meningitis. The disease can be prevented by a single dose of meningococcal vaccine. We carried out a randomized observer-blinded non-inferiority trial to evaluate and compare the immunogenicity and safety of a local meningococcal polysaccharide vaccine 'Ingovax ACWY' (test) with Quadri Meningo TM (comparator), an approved meningococcal polysaccharide vaccine in India. A total of 88 healthy adults (18-45 years old) were randomized at a 1:1 ratio in two vaccine groups receiving a single dose vaccine subcutaneously. All participants were followed until three months post-vaccination. Blood for clinical parameters (hematology and biochemistry) and serum bactericidal assay (SBA) was collected prior to vaccination and one-month post-vaccination. Solicited adverse events (AEs) were assessed up to 6 days following vaccination and unsolicited AEs were monitored throughout the follow-up period. There was no significant difference in rates of AE between the two groups. The commonest solicited AE was injection site pain. No serious AEs were reported. There was no significant difference (p<0.05) in seroconversion rate as well as pre and post-vaccination SBA geometric mean titers (GMT)between test and comparator vaccine. The post-vaccination GMT ratio (GMR) of the test and comparator vaccine was found to be 0.9, 1, 1.29, and 0.85 for serogroup A, C, W135, and Y respectively. For all the serogroups, lower limit of 95% CI of the GMR was found to be greater than the pre-defined 0.5 non-inferiority margin suggesting that Ingovax ACWY is similar to Quadri Meningo TM vaccine. We observed the immunogenicity and safety of Ingovax ACWY is non-inferior to comparator vaccine. The development of facilities for manufacturing polysaccharide ACWY vaccines locally will further lead to capacity building in the field of vaccines for Bangladesh., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

The four-component recombinant-DNA anti-meningococcus B vaccine (4CMenB) has been approved by the European Medicines Agency in 2013. In Italy, 4CMenB is recommended since 2017 for use in infants under one year of age. Due to the strong evidence of increased risk of fever after administration, surveillance of adverse events following immunization (AEFIs) is a priority for 4CMenB. This cross-sectional prospective study aims at investigating 4CMenB's safety profile. The study population is represented by infants under twelve months of age vaccinated with 4CMenB in selected ambulatories in Apulia, a region in South-Eastern Italy, from October 1st, 2020, to March 31st, 2023. Parents were provided with a post-vaccination diary covering up to seven days after immunization and were contacted one week after the vaccination day. Information about AEFIs was collected, and reactions were classified following World Health Organization guidelines. For serious AEFIs, causality assessment was carried out. AEFI risk determinants were investigated via logistic regression. A total of 4,773 diaries were completed, with 78.13 % of them (3,729/4,773) containing one or more AEFI reports. Systemic reactions such as malaise, drowsiness/insomnia and fatigue were the most common ones, followed by fever and local pain, tenderness, redness and swelling. Twenty-three cases of serious AEFIs were reported. Following causality assessment, 78.26 % of serious adverse events (18/23) were deemed to have a consistent causal association with the administration of 4CMenB (reporting rate: 0.38 %). Three infants were hospitalized following vaccination, but no cases of death or permanent/severe impairment were reported. Prophylactic paracetamol administration showed a significant protective effect against the risk of manifesting fever within the first 24 h after administration (OR: 0.75; p < 0.005). Our data confirms existing evidence regarding the safety of 4CMenB vaccination in babies under 2 years of age, but also highlight a significant risk of fever after vaccination. Prophylactic paracetamol administration could represent a protective factor against fever, especially during the first 24 h after vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The immunogenicity and safety of a booster dose of tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT), alone or co-administered with MenB vaccine, were assessed in healthy 13-25-year olds who received MenACYW-TT or a CRM-conjugate vaccine (MCV4-CRM) 3-6 years earlier., Methods: This phase IIIb open-label trial (NCT04084769) evaluated MenACYW-TT-primed participants, randomized to receive MenACYW-TT alone or with a MenB vaccine, and MCV4-CRM-primed participants who received MenACYW-TT alone. Functional antibodies against serogroups A, C, W and Y were measured using human complement serum bactericidal antibody assay (hSBA). The primary endpoint was vaccine seroresponse (post-vaccination titers ≥1:16 if pre-vaccination titers <1:8; or a ≥4-fold increase if pre-vaccination titers ≥1:8) 30 days post booster. Safety was evaluated throughout the study., Results: The persistence of the immune response following primary vaccination with MenACYW-TT was demonstrated. Seroresponse after MenACYW-TT booster was high regardless of priming vaccine (serogroup A: 94.8% vs 93.2%; C: 97.1% vs 98.9%; W: 97.7% vs 98.9%; and Y; 98.9% vs 100% for MenACWY-TT-primed and MCV4-CRM-primed groups, respectively). Co-administration with MenB vaccines did not affect MenACWY-TT immunogenicity. No vaccine-related serious adverse events were reported., Conclusions: MenACYW-TT booster induced robust immunogenicity against all serogroups, regardless of the primary vaccine received, and had an acceptable safety profile., Impact: A booster dose of MenACYW-TT induces robust immune responses in children and adolescents primed with MenACYW-TT or another MCV4 (MCV4-DT or MCV4-CRM), respectively. Here, we demonstrate that MenACYW-TT booster 3-6 years after primary vaccination induced robust immunogenicity against all serogroups, regardless of the priming vaccine (MenACWY-TT or MCV4-CRM), and was well tolerated. Persistence of the immune response following previous primary vaccination with MenACYW-TT was demonstrated. MenACYW-TT booster with MenB vaccine co-administration did not affect MenACWY-TT immunogenicity and was well tolerated. These findings will facilitate the provision of broader protection against IMD particularly in higher-risk groups such as adolescents., (© 2023. The Author(s).)

Background: People living with HIV have been shown to have an increased risk of invasive meningococcal disease. In some countries, meningococcal vaccines are now routinely recommended to all people living with HIV, but no study has yet assessed the immunogenicity and safety of a meningococcal serogroup B vaccine or the co-administration of a MenB and MenACWY vaccine in people living with HIV., Methods: This phase IV open-label clinical trial investigated the immunogenicity and safety 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 a population of people living with HIV. Immunogenicity analysis was performed before vaccination and 1 month after the second doses of 4CMenB and MenACWY. Primary outcome measures were serum bactericidal assay geometric mean titres against three MenB reference strains at baseline and 1 month post vaccination, the proportion of participants achieving a putative protective titre of ≥4, and the proportion of participants with a ≥4-fold rise in titre from baseline. Secondary outcome measures were serum bactericidal assay geometric mean titres against MenA, C, W, and Y reference strains at baseline and 1 month post vaccination, the proportion achieving a putative protective titre of ≥8, and the proportion with a ≥4-fold rise in titre from baseline. Safety outcomes were solicited and unsolicited adverse events in the 7 days following vaccination. The trial was registered with clinicaltrials.gov (NCT03682939)., Findings: In total, 55 participants aged 20-45 years were enrolled. All participants (100%; 95% confidence interval [CI] 93-100) achieved putative protective titres for two of the three MenB strains and for MenA, W, and Y. A total of 98% (95% CI 89-100) achieved a protective titre for the third MenB strain and 94% (95% CI 83-99) for MenC. No serious adverse events were reported., Interpretation: 4CMenB and MenACWY were immunogenic and well-tolerated in a population of people living with HIV 1 month after two doses., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

The four-component meningococcal serogroup B vaccine (4CMenB) is indicated for the prevention of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B. Co-administering 4CMenB with other vaccines may improve vaccine uptake provided that the safety and immunogenicity of either are not affected. Published literature on the immunogenicity and reactogenicity of 4CMenB co-administered with other routine childhood and adulthood vaccines was reviewed. From 282 publications identified, data were collated from 10 clinical studies, 3 real-world studies, and 3 reviews. The evidence showed that 4CMenB co-administration is not associated with significant safety concerns or clinically relevant immunological interferences. The increased reactogenicity (e.g., fever) associated with 4CMenB co-administration can be adequately managed with prophylactic paracetamol in children. Thus, 4CMenB co-administration has the potential to maximize vaccine coverage and improve protection against IMD globally.

Background: Immunization with meningococcal ACWY conjugate vaccine induces protective antibodies against invasive meningococcal disease (IMD) caused by serogroups A, C, W and Y. We studied MenACWY-TT vaccine immunogenicity in adolescents with a heterogenous group of primary and secondary immune deficiency including patients with systemic lupus erythematosus, mixed connective tissue disease, vasculitis, uveitis, 22Q11 syndrome, sickle cell disease, and patients who underwent stem cell transplantation for bone marrow failure., Findings: We enrolled 69 individuals aged 14-18 years diagnosed with a primary or secondary immune deficiency in a prospective observational cohort study. All patients received a single dose of MenACWY-TT vaccine during the catch-up campaign 2018-19 because of the IMD-W outbreak in the Netherlands. Capsular polysaccharide-specific (PS) IgG concentrations against MenACWY were measured before and 3-6, 12, and 24 months after vaccination. Overall, geometric mean concentrations (GMCs) of MenACWY-PS-specific IgG were lower in patients compared to data from healthy, aged-matched controls (n = 75) reaching significance at 12 months postvaccination for serogroup A and W (adjusted GMC ratios 0.26 [95% CI: 0.15-0.47] and 0.22 [95% CI: 0.10-0.49], respectively). No serious adverse events were reported by study participants., Conclusions: The MenACWY conjugate vaccine was less immunogenic in adolescent patients with primary or secondary immunodeficiency compared to healthy controls, urging the need for further surveillance of these patients and supporting considerations for booster MenACWY conjugate vaccinations in these patient groups., (© 2023. The Author(s).)

Background: Immunogenicity to meningococcal serogroup ACWY (MenACWY) conjugate vaccine has not been studied in immunocompromised minors with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD). We determined immunogenicity of a MenACWY-TT vaccine in JIA and IBD patients at adolescent age and compared results to data from aged-matched healthy controls (HCs)., Methods: We performed a prospective observational cohort study in JIA and IBD patients (14-18 years old), who received a MenACWY vaccination during a nationwide catch-up campaign (2018-2019) in the Netherlands. Primary aim was to compare MenACWY polysaccharide-specific serum IgG geometric mean concentrations (GMCs) in patients with HCs and secondary between patients with or without anti-TNF therapy. GMCs were determined before and 3-6, 12, and 24 months postvaccination and compared with data from HCs at baseline and 12 months postvaccination. Serum bactericidal antibody (SBA) titers were determined in a subset of patients at 12 months postvaccination., Results: We included 226 JIA and IBD patients (66 % and 34 % respectively). GMCs were lower for MenA and MenW (GMC ratio 0·24 [0·17-0·34] and 0·16 [0·10-0·26] respectively, p < 0·01) in patients compared to HCs at 12 months postvaccination. Anti-TNF users had lower MenACWY GMCs postvaccination compared with those without anti-TNF (p < 0·01). The proportion protected (SBA ≥ 8) for MenW was reduced in anti-TNF users (76 % versus 92 % in non-anti-TNF and 100 % in HCs, p < 0.01)., Conclusion: The MenACWY conjugate vaccine was immunogenic in the vast majority of JIA and IBD patients at adolescent age, but seroprotection was lower in patients using anti-TNF agents. Therefore, an extra booster MenACWY vaccination should be considered., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Acute cerebellar ataxia (ACA) and acute cerebellitis represent disorders characterized by a para-infectious, post-infectious, or post-vaccination cerebellar inflammation. They are relatively common neurologic disorders among children, and may follow infections, or, more rarely, vaccinations. Few cases are instead described among infants. Although the immunization with meningococcal group B (MenB) vaccine has been associated with some neurological side effects, suspected ACA has been reported only once in the literature., Case Presentation: we describe a 7-month-old female that presented ACA within 24 h from the MenB second dose vaccination. Extensive laboratory studies and magnetic resonance imaging excluded other causes. We then conducted an extended review of other vaccine related cases reported in the literature, focusing on the clinical characteristics of ACA and finding that ataxia and cerebellitis of para- or post-infectious cause are very rarely described in the first year of life. We collected 20 articles published in the last 30 years, including an amount of 1663 patients (1-24 years) with ACA., Conclusions: a very small number of suspected post-vaccinal ataxias has been described in recent years, compared to other causes, and vaccination remains an unquestionable medical need. Further research is needed to clarify the complex pathogenesis of this disorder and its eventual link with vaccinations., (© 2023. The Author(s).)

Country-wide social distancing and suspension of non-emergency medical care due to the COVID-19 pandemic will undoubtedly have affected public health in multiple ways. While non-pharmaceutical interventions are expected to reduce the transmission of several infectious diseases, severe disruptions to healthcare systems have hampered diagnosis, treatment, and routine vaccination. We examined the effect of this disruption on meningococcal disease and vaccination in the UK. By adapting an existing mathematical model for meningococcal carriage, we addressed the following questions: What is the predicted impact of the existing MenACWY adolescent vaccination programme? What effect might social distancing and reduced vaccine uptake both have on future epidemiology? Will catch-up vaccination campaigns be necessary? Our model indicated that the MenACWY vaccine programme was generating substantial indirect protection and suppressing transmission by 2020. COVID-19 social distancing is expected to have accelerated this decline, causing significant long-lasting reductions in both carriage prevalence of meningococcal A/C/W/Y strains and incidence of invasive meningococcal disease. In all scenarios modelled, pandemic social mixing effects outweighed potential reductions in vaccine uptake, causing an overall decline in carriage prevalence from 2020 for at least 5 years. Model outputs show strong consistency with recently published case data for England.

Background: An effective, affordable, multivalent meningococcal conjugate vaccine is needed to prevent epidemic meningitis in the African meningitis belt. Data on the safety and immunogenicity of NmCV-5, a pentavalent vaccine targeting the A, C, W, Y, and X serogroups, have been limited., Methods: We conducted a phase 3, noninferiority trial involving healthy 2-to-29-year-olds in Mali and Gambia. Participants were randomly assigned in a 2:1 ratio to receive a single intramuscular dose of NmCV-5 or the quadrivalent vaccine MenACWY-D. Immunogenicity was assessed at day 28. The noninferiority of NmCV-5 to MenACWY-D was assessed on the basis of the difference in the percentage of participants with a seroresponse (defined as prespecified changes in titer; margin, lower limit of the 96% confidence interval [CI] above -10 percentage points) or geometric mean titer (GMT) ratios (margin, lower limit of the 98.98% CI >0.5). Serogroup X responses in the NmCV-5 group were compared with the lowest response among the MenACWY-D serogroups. Safety was also assessed., Results: A total of 1800 participants received NmCV-5 or MenACWY-D. In the NmCV-5 group, the percentage of participants with a seroresponse ranged from 70.5% (95% CI, 67.8 to 73.2) for serogroup A to 98.5% (95% CI, 97.6 to 99.2) for serogroup W; the percentage with a serogroup X response was 97.2% (95% CI, 96.0 to 98.1). The overall difference between the two vaccines in seroresponse for the four shared serogroups ranged from 1.2 percentage points (96% CI, -0.3 to 3.1) for serogroup W to 20.5 percentage points (96% CI, 15.4 to 25.6) for serogroup A. The overall GMT ratios for the four shared serogroups ranged from 1.7 (98.98% CI, 1.5 to 1.9) for serogroup A to 2.8 (98.98% CI, 2.3 to 3.5) for serogroup C. The serogroup X component of the NmCV-5 vaccine generated seroresponses and GMTs that met the prespecified noninferiority criteria. The incidence of systemic adverse events was similar in the two groups (11.1% in the NmCV-5 group and 9.2% in the MenACWY-D group)., Conclusions: For all four serotypes in common with the MenACWY-D vaccine, the NmCV-5 vaccine elicited immune responses that were noninferior to those elicited by the MenACWY-D vaccine. NmCV-5 also elicited immune responses to serogroup X. No safety concerns were evident. (Funded by the U.K. Foreign, Commonwealth, and Development Office and others; ClinicalTrials.gov number, NCT03964012.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Three hexavalent (DTaP-IPV-Hib-HepB) vaccines are licensed in Europe, only one of which (Vaxelis, Hex-V), uses a meningococcal outer membrane protein complex as a carrier protein for Hemophilus influenza type b (Hib), creating potential interactions with the meningococcal vaccine 4CMenB., Methods: In this single-center open-label randomized trial, infants were randomized in a 1:1 ratio to receive Hex-V or an alternative hexavalent vaccine (Infanrix-Hexa, Hex-IH) at 2, 3, and 4 months with 4CMenB (2, 4, and 12 months) in the UK routine immunization schedule. The primary outcome was noninferiority of geometric mean concentrations (GMCs) of anti-PRP (Hib) IgG at 5 months of age. Secondary outcomes included safety, reactogenicity, and immunogenicity of other administered vaccines measured at 5 and 13 months of age., Results: Of the 194 participants enrolled, 96 received Hex-V and 98 Hex-IH. Noninferiority of anti-PRP IgG GMCs at 5 months of age in participants receiving Hex-V was established; GMCs were 23-times higher following three doses of Hex-V than three doses of Hex-IH (geometric mean ratio (GMR) 23.25; one-sided 95% CI 16.21, -). 78/85 (92%) of Hex-V recipients and 43/87 (49%) of Hex-IH recipients had anti-PRP antibodies ≥1.0 µg/mL. At 5 months of age serum, bactericidal activity titers against MenB strain 5/99 were higher following Hex-V than Hex-IH (GMR 1.56; 95% CI, 1.13-2.14). The reactogenicity profile was similar in both groups., Conclusions: These data support flexibility in the use of either Hex-IH or Hex-V in infant immunization schedules containing 4CMenB, with the possibility that Hex-V may enhance protection against Hib., Competing Interests: MDS acts on behalf of the University of Oxford as an Investigator on clinical trials funded or otherwise supported by vaccine manufacturers including MCM vaccines, Janssen, GlaxoSmithKline, Novavax, AstraZeneca and Pfizer. He receives no direct personal financial payment for this work. For remaining authors, there are no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Since the multicomponent meningococcal B vaccine introduction, the Apulian Regional Health Authority implemented postmarketing surveillance program, as provided by Italian laws.From National Pharmacovigilance Network, we selected 4CMenB AEFIs reported in Apulia from 01 January 2014 to 31 December 2019, while the number of 4 cMen B doses administered per year was obtained from the regional immunization database (GIAVA).For each subject who experienced an adverse event following meningococcal B vaccine (AEFIs), a predefined form was filled in.A total of 214 AEFIs (26.5 × 100.000 doses) were reported after any dose of MenB-4 c vaccination of which 58/214 (27.1%) were classified as serious (7.2 × 100,000 doses), 145/214 (67.8%) as not serious (180 × 100,000 doses), and 11/214 (5.1%) as undefined (1.3 × 100,000 doses).The average age of subjects who experimented and AEFI was 30 months. The majority of serious AEFIs were reported in 2- to 11-month-old children (44/57; 77.2%). A total of 31/58 (3.8 × 100,000 doses; 53.4%) serious AEFIs were reported as having a 'consistent causal association' with vaccination. Of these, fever/hyperpyrexia was reported in 21/31 (2.6 × 100,000 doses; 67.7%); hypotonic-hyporesponsive episode was reported in 7/31 (0.9 × 100,000 doses [add %-age]) and was the most frequent adverse event with neurological symptoms. A total of 13/31 (41.9%) serious AEFIs classified as 'consistent causal association' were reported after the first dose of 4cMenB, of these 5/13 (38.5%) children did not complete the vaccination schedule.Our data seemed to confirm, in a large population, the a good safety profile of the universal mass vaccination with 4CMENB.

Booster doses of meningococcal conjugate vaccines induce long-term protection against invasive meningococcal disease. We evaluated the immunogenicity and safety of a booster dose of MenACYW-TT in pre-school children who were primed 3 years earlier with MenACYW-TT or MCV4-TT (Nimenrix®). In this Phase III, open-label, multi-center study (NCT03476135), children (4-5 years old), who received a primary dose of MenACYW-TT or MCV4-TT as toddlers in a previous study, received a booster dose of MenACYW-TT. Titers of antibody against meningococcal serogroups A, C, W and Y were measured by serum bactericidal assay using human (hSBA) and baby rabbit (rSBA) complement in samples collected before (D0) and 30 days after (D30) booster vaccination. Safety was assessed over the 30-day study period. Ninety-one participants received the booster dose. In both study groups, hSBA titers increased from D0 to D30; serogroup C titers [95% confidence interval] were higher in the MenACYW-TT-primed vs MCV4-TT-primed group at D0 (106 [73.2, 153] vs 11.7 [7.03, 19.4], respectively) and D30 (5894 [4325, 8031] vs 1592 [1165, 2174], respectively); rSBA results were similar. Nearly all participants achieved ≥1:8 hSBA and rSBA titers at D30, which were higher or comparable to those observed post-primary dose, suggesting rapid booster responses. At D0, all hSBA and rSBA titers were higher than those observed pre-primary dose, suggesting persistence of immunogenicity. The MenACYW-TT booster dose was well-tolerated and had similar safety outcomes across study groups. These findings suggest that MenACYW-TT elicits robust booster responses in children primed 3 years earlier with MenACYW-TT or MCV4-TT.

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 meningococcal serogroups A, C, W, and Y tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix®; Pfizer Ltd, Sandwich, Kent, UK) is licensed in more than 80 countries worldwide for the prevention of meningococcal disease caused by serogroups A, C, W, and Y in individuals throughout their lifespans. This report summarizes safety data from the MenACWY-TT clinical development program and postmarketing experience., Methods: Within the clinical study program, reactogenicity data were based on 3 primary studies, including a large pooled analysis across multiple age groups, and long-term safety data were derived from 3 studies evaluating long-term antibody persistence. Postmarketing safety data through April 19, 2021, were collected and analyzed in connection with the MenACWY-TT Periodic Safety Update Report., Results: Approximately 32 million doses of MenACWY-TT have been administered worldwide, with more than 21,530 additional individuals receiving MenACWY-TT as part of clinical trials. The safety profile of MenACWY-TT was consistent between the clinical study program and the postmarketing experience, as well as with other licensed meningococcal vaccines. The most commonly observed adverse events (AEs) were pyrexia/fever, headache, injection site pain/reactions, nausea/vomiting, and fatigue; serious AEs were rare relative to the number of doses administered. Several cases of serogroup replacement/lack of efficacy were observed in the 1-year postmarketing period but did not appear to be related to MenACWY-TT use., Conclusion: Extensive data derived from clinical trials and postmarketing experience indicate a consistently favorable safety profile for MenACWY-TT across a wide range of age groups., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors are employees of Pfizer Inc and may hold stock or stock options., (Copyright © 2022 The Pfizer Inc, The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Differentiating infants with adverse events following immunisation (AEFIs) or invasive bacterial infection (IBI) is a significant clinical challenge. Young infants post vaccination are therefore often admitted to the hospital for parenteral antibiotics to avoid missing rare cases of IBI., Methods: During a service evaluation project, we conducted a single-centre retrospective observational study of infants with IBI, urinary tract infection (UTI) or AEFI from two previously published cohorts. All patients presented to hospital in Oxfordshire, UK, between 2011 and 2018, spanning the introduction of the capsular group-B meningococcal vaccine (4CMenB) into routine immunisation schedules. Data collection from paper and electronic notes were unblinded. Clinical features, including National Institute for Health and Care Excellence (NICE) 'traffic light' risk of severe illness and laboratory tests performed on presentation, were described, and comparisons made using regression models, adjusting for age and sex. We also compared biochemical results on presentation to those of well infants post vaccination, with and without 4CMenB regimens., Results: The study included 232 infants: 40 with IBI, 97 with probable AEFI, 24 with possible AEFI, 27 with UTI and 44 post vaccination 'well' infants. C-reactive protein (CRP) was the only discriminatory blood marker, with CRP values above 83 mg/L only observed in infants with IBI or UTI. NICE risk stratification was significantly different between groups but still missed cases of IBI, and classification as intermediate risk was non-differential. Fever was more common in probable AEFI cases, while seizures and rashes were equally frequent. Diarrhoea and clinician-reported irritability or rigours were all more common in IBI., Conclusions: Clinical features on presentation may aid risk stratification but cannot reliably differentiate IBI from AEFI in infants presenting to the emergency department. Blood results are generally unhelpful due to post vaccination inflammatory responses, particularly in children receiving 4CMenB vaccination. Improved biomarkers and clinical prediction tools are required to aid management in febrile infants post vaccination., Competing Interests: Competing interests: MDS acts as a chief/principal investigator on clinical trials funded by vaccine manufacturers including GSK group of companies, Novavax, Medimmune, MCM, Pfizer, Janssen and AstraZeneca. These studies are conducted on behalf of the University of Oxford and MDS received no personal financial benefit. MDS is also a member of medical advisory boards for the Meningitis Research Foundation. DO’C received honoraria as a reviewer for The Lancet Infectious Diseases journal and is on the journal editorial boards for the following journals: Clinical & Experimental Immunology, Frontiers in Immunology and Journal of Immunological Research., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: In the United States, individuals with HIV infection have been recommended to receive a 2-dose series of the meningococcal A, C, W, Y (MenACWY) vaccine since 2016 owing to their increased risk of meningococcal disease., Objective: To examine uptake and time to receipt of the MenACWY vaccine among people with a new diagnosis of HIV., Design, Setting, and Participants: This cohort study used health insurance data from the US Optum Research Database from January 1, 2016, through March 31, 2018, to retrospectively identify 1208 individuals aged 2 years or older with 1 or more inpatient claim or 2 or more outpatient claims evidencing a new diagnosis of HIV infection and with continuous insurance enrollment for 12 or more months before and 6 or more months after diagnosis. Follow-up was 6 to 33 months. Statistical analysis was conducted from March 7, 2019, to January 5, 2022., Exposure: Receipt of the MenACWY vaccine., Main Outcomes and Measures: The coprimary outcomes were uptake and time to receipt of 1 or more doses of the MenACWY vaccine after a new HIV diagnosis. Secondary outcomes included uptake and time to receipt of 2 or more doses of the MenACWY vaccine. Vaccination uptake and receipt were estimated by Kaplan-Meier analysis; factors associated with receipt of 1 or more doses of the MenACWY vaccine were identified with multivariable Cox proportional hazards regression analysis., Results: Of 1208 individuals eligible for vaccination (1024 male patients [84.8%]; mean [SD] age, 38.8 [12.5] years; 35 [2.9%] Asian; 273 [22.6%] Black; 204 [16.9%] Hispanic; 442 [36.6%] White), 16.3% were estimated to have received a first dose of the MenACWY vaccine in the 2 years after a new HIV diagnosis. Among individuals who received a first dose, at 1 year or more of enrollment after the first dose, 66.2% were estimated to have received a second dose within 1 year of the first dose. Factors statistically significantly associated with uptake of the MenACWY vaccine included receipt of a pneumococcal vaccine (hazard ratio [HR], 23.03; 95% CI, 13.93-38.09), attendance at a well-care visit (HR, 3.67; 95% CI, 1.11-12.12), West or Midwest geographic region (West: HR, 2.24; 95% CI, 1.44-3.47; Midwest: HR, 1.78; 95% CI, 1.16-2.71), and male sex (HR, 2.72; 95% CI, 1.18-6.26), whereas age of 56 years or older was significantly associated with reduced uptake of the MenACWY vaccine (HR, 0.42; 95% CI, 0.18-0.97)., Conclusions and Relevance: This cohort study suggests that MenACWY vaccine uptake among people with a new diagnosis of HIV was low, highlighting the need to educate patients and clinicians about the recommendations for conditions such as HIV infection that increase the risk of meningococcal disease among high-risk populations.

Background: The MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10-65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size. The current safety analysis evaluates pooled reactogenicity and other adverse events (AEs) reported in these trials to identify new safety signals not detectable in individual trials., Methods: Eleven trials contributed safety data, of which 10 recorded local and systemic reactogenicity events; 8 of the trials were controlled, and reactogenicity data were pooled for 7 of these 8 trials. Additional AE evaluations included immediate AEs (IAEs), medically attended AEs (MAEs), serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), and autoimmune or neuroinflammatory conditions., Results: Local and systemic reactions were more frequent in the MenB-FHbp group (n = 15,294) compared with controls (n = 5509), although most reactions were transient and mild to moderate in severity. Frequencies of IAEs, SAEs, MAEs, NDCMCs, and autoimmune or neuroinflammatory conditions were similar between the MenB-FHbp and control groups., Conclusions: MenB-FHbp demonstrated a favorable safety and tolerability profile in the clinical development program of > 15,000 vaccine recipients ≥ 10 years of age. No new safety signals were identified in the pooled analysis compared with data from the individual trials. Continued postmarketing safety surveillance is important for the identification of rare events. Clinicaltrials.gov: NCT01299480; NCT000808028; NCT00879814; NCT00780806; NCT01352845; NCT01352793; NCT01461993; NCT01323270; NCT01830855; NCT01461980; NCT01768117., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: All authors are employees or former employees of Pfizer Inc and may hold stock or stock options., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Between May 2005 and March 2007, three vaccines were recommended by the Advisory Committee on Immunization Practices for routine use in adolescents in the United States: quadrivalent meningococcal conjugate vaccine (MenACWY), tetanus, diphtheria and acellular pertussis vaccine (Tdap), and human papillomavirus vaccine (HPV). Understanding historical adolescent vaccination patterns may inform future vaccination coverage efforts for these and emerging adolescent vaccines, including COVID-19 vaccines., Methods: This was a descriptive, retrospective cohort study. All vaccines administered to adolescents aged 11 through 18 years in the Vaccine Safety Datalink population between January 1, 2007 and December 31, 2016 were examined. Vaccination coverage was assessed by study year for ≥1 dose Tdap or Td, ≥1 dose Tdap, ≥1 dose MenACWY, ≥1 dose HPV, and ≥3 dose HPV. The proportion of vaccine visits with concurrent vaccination (≥2 vaccines administered at the same visit) was calculated by sex and study year. The most common vaccine combinations administered in the study population were described by sex for two time periods: 2007-2010 and 2011-2016., Results: The number of 11-18-year-olds in the study population averaged 522,565 males and 503,112 females per study year. Between January 2007 and December 2016 there were 4,884,553 vaccine visits in this population (45% among males). The overall proportion of concurrent vaccine visits among males was 43% (33-61% by study year). Among females, 39% of all vaccine visits included concurrent vaccination (32-48% by study year). Vaccine coverage for Tdap, MenACWY, and 1- and 3-dose HPV increased across the study period. A wide variety of vaccine combinations were administered among both sexes and in both time periods., Conclusions: The high vaccine uptake and multitude of vaccine combinations administered concurrently in the adolescent population of the Vaccine Safety Datalink provide historical patterns with which to compare future adolescent vaccination campaigns., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ms. Irving, Ms. Groom, Ms. Dandamudi, Drs. Daley, Myers, Stokley and Ms. Gee have no conflicts to report. Dr. Donahue reports receiving grants from Janssen Vaccines & Prevention outside the submitted work. Dr. Hechter reports grants from Gilead Science Inc and Novartis for research studies outside the submitted work. Dr. Jackson reports an organization research contract with Pfizer, outside the submitted work. Dr. Klein reports grants from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Sciences (now Sanofi Pasteur), outside the submitted work. Dr. Liles reports research funding from Merck, Pfizer, Epigenomics, and Medical Solutions, outside the submitted work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Bexsero® (GlaxoSmithKline) is a four-component Neisseria meningitidis serogroup B vaccine (MenB-4C). It was licensed in the United States in 2015 for use among individuals ages 10-25 years. We aimed to assess the post-licensure safety profile of MenB-4C by examining reports received in the Vaccine Adverse Event Reporting System (VAERS)., Methods: VAERS is a national passive surveillance system for adverse events (AEs) following immunization that uses the Medical Dictionary for Regulatory Activities to code reported AEs and the Code of Federal Regulations to classify reports by seriousness. In this case series, we analyzed U.S. reports involving MenB-4C received between January 23, 2015 through December 31, 2018. We used Empirical Bayesian data mining to identify MenB-4C/AE combinations reported at least twice as often as expected., Results: VAERS received 1,867 reports following MenB-4C administration, representing 332 reports per million doses distributed. Most reports were for females (59%), with a median age of 17 years (interquartile range: 16-18 years); 40% of reports described simultaneous administration of other vaccines. The majority of reports were classified as non-serious (96%). The most commonly reported AEs were injection site pain (22%), pyrexia (16%), and headache (16%). Data mining identified disproportionate reporting for "injected limb mobility decreased" secondary to injection site reactions, including extensive swelling of the vaccinated limb and injection site pain., Conclusions: Analysis of passive surveillance data from over 5.6 million doses of MenB-4C distributed in the United States did not reveal new safety concerns. The large majority of reports were classified as non-serious and the reported AEs were generally consistent with the safety experience described in clinical studies and the product's package insert. While our results are reassuring, continued post-marketing surveillance is warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: The MenB-FHbp vaccine is licensed to prevent meningococcal serogroup B disease on either a 2-dose (0, 6 months) or 3-dose (0, 1-2, 6 months) series. This phase 3 study further assessed the immunogenicity and safety of the 2-dose MenB-FHbp schedule., Methods: Subjects 10-25 years of age received MenB-FHbp (months 0, 6) and the quadrivalent meningococcal conjugate vaccine MenACWY-CRM (month 0). Primary immunogenicity endpoints included percentages of subjects achieving ≥ 4-fold increases from baseline in serum bactericidal antibody using human complement (hSBA) titers for 4 diverse, vaccine-heterologous primary serogroup B test strains and titers ≥ lower limit of quantitation (LLOQ; 1:8 or 1:16) for all 4 primary strains combined (composite response) after dose 2; a titer ≥ 1:4 is the accepted correlate of protection. Percentages of participants with hSBA titers ≥ LLOQ for 10 additional vaccine-heterologous strains were also assessed; positive predictive values of primary strain responses for secondary strain responses were determined. Safety was assessed., Results: Overall, 1057 subjects received dose 1 and 946 received dose 2 of MenB-FHbp. Percentages of participants achieving ≥ 4-fold increases in hSBA titers against each primary strain after dose 2 ranged from 67.4% to 95.0% and the composite response was 74.3%. Primary strain responses were highly predictive of secondary strain responses. Most reactogenicity events were mild-to-moderate in severity and did not lead to withdrawal from the study. Adverse events (AEs) considered by the investigator to be related to vaccination occurred in 4.2% (44/1057) of subjects, and there were no serious AEs or newly diagnosed chronic medical conditions considered related to vaccination., Conclusions: MenB-FHbp administered at 0, 6 months was well tolerated and induced protective bactericidal antibody responses against diverse serogroup B strains. Findings provide further support for the continued use of MenB-FHbp on a 2-dose schedule in this population., Competing Interests: Declaration of Competing Interest Daniel Drazan and Hanna Czajka are investigators in Pfizer clinical studies. All other authors are current employees of Pfizer and may hold stock or stock options in the company., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This phase 2, randomized, open-label study assessed the immunogenicity and safety of an investigational meningococcal ABCWY vaccine (MenABCWY) that contains components of licensed vaccines against meningococcal serogroup B (4CMenB) and serogroups ACWY (MenACWY). A total of 500 healthy 10- to 25-year-old participants were randomly assigned to one of five study groups in a 1:1:1:1:1 ratio. Four groups received two doses 2 months apart of MenABCWY and 4CMenB plus MenACWY administered concomitantly in the same arm (4CMenB+ACWY/S group) or different arms (4CMenB+ACWY/D group) or 4CMenB administered alone. A fifth group received a single MenACWY dose. Immunogenicity was determined by serum bactericidal assay using human complement (hSBA). The study was powered to assess immunological interference against pooled serogroup B test strains. One month after the second vaccine dose, hSBA geometric mean titers (GMTs) (with 80% confidence intervals [CI]) against pooled serogroup B strains were 31.84 (80% CI, 28.18 to 35.98), 38.48 (80% CI, 34.23 to 43.26), 40.08 (80% CI, 35.44 to 45.33), and 42.38 (80% CI, 37.31 to 48.13) in the MenABCWY, 4CMenB+ACWY/S, 4CMenB+ACWY/D, and 4CMenB groups, respectively. Immune responses (GMTs and 80% CIs) were lower for PorA and NHBA serogroup B test strains in the MenABCWY group compared to the 4CMenB+ACWY/D group and 4CMenB group. Evaluation of solicited and unsolicited adverse events (AEs) identified no safety concerns for the MenABCWY vaccine. One serious AE (syncope in the 4CMenB group) was considered related to vaccination. In conclusion, there is no evidence of substantial immunological interference between 4CMenB and MenACWY vaccine components against serogroup B. The safety and tolerability profile of the investigational MenABCWY vaccine was acceptable. (This study has been registered at ClinicalTrials.gov under registration no. NCT03587207.) IMPORTANCE The bacterial species Neisseria meningitidis is a major cause of meningitis, with six meningococcal groups (serogroups) causing most cases. A licensed vaccine, MenACWY (Menveo), targets four of these meningococcal serogroups, and another vaccine, 4CMenB (Bexsero), targets serogroup B. A combined vaccine (MenABCWY) that targets all five serogroups is under development to simplify the vaccination schedule. In a previous study, the immune response to serogroup B was found to be overall higher in individuals who received 4CMenB than in those who received an investigational MenABCWY vaccine. We investigated this further by giving healthy adolescents and young adults the MenABCWY vaccine, 4CMenB plus MenACWY vaccine in the same or different arms, 4CMenB vaccine alone, or MenACWY vaccine alone. Immunogenicity results for serogroup B across study groups suggest no major interference between the MenB and MenACWY vaccine components. This supports further development of the combined MenABCWY vaccine.

The meningococcal serogroup B (MenB) protein vaccine, 4CMenB, combined with MenA, MenC, MenW and MenY polysaccharide-protein conjugates for a pentavalent MenABCWY vaccine, can potentially protect against most causative agents of invasive meningococcal disease worldwide. Two phase 2b, randomized, multicenter studies were conducted (NCT02212457, NCT02946385) to assess the immunogenicity and safety of the MenABCWY vaccine as well as antibody persistence and response to a booster dose 2 years after the last vaccination, compared to 4CMenB vaccination. Participants (10 - 18 years), randomized (3:3:2:2:2:2), received the 4-component 4CMenB vaccine according to a 0-2 month (M) schedule or MenABCWY according to a 0-2, 0-6, 0-2-6, 0-1, or 0-11 M schedule. All participants received 5 injections (at M0, M1, M2, M6 and M12) with either the study vaccines or placebo/hepatitis A vaccine. Follow-on participants (4CMenB-0-2, MenABCWY-0-2, MenABCWY-0-6 and MenABCWY-0-2-6 groups) received one dose of either 4CMenB (4CMenB-0-2 group) or MenABCWY and newly enrolled, age-matched, meningococcal vaccine-naïve adolescents (randomized 1:1) received 2 doses (0-2 M) of either 4CMenB or MenABCWY. MenABCWY vaccination was immunogenic against MenB test strains. Non-inferiority for all 4 components of the 4CMenB vaccine could not be demonstrated for the 0-2 M schedule. Antibodies persisted up to 2 years post-MenABCWY vaccination and a booster dose induced an anamnestic response as higher titers were observed in follow-on participants compared to the first-dose response in vaccine-naïve participants. MenABCWY had a clinically-acceptable safety profile, not different from that of 4CMenB.

Meningococcal disease by serogroup B has been a public health problem in Brazil in the last decades. The Brazilian Oswaldo Cruz Foundation has been working to develop a vaccine with detergent-treated outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. A phase I study, enrolling 26 adults (18-44 years of age) was performed using experimental vaccines combining B components and aluminum hydroxide as adjuvant. It was a dose escalation study testing vaccines made of 25, 50, and 100 µg OMV protein/mL (sum of both strains) and dLOS in half amount of total protein concentration, with three doses given two months apart. Adverse events were mild/moderate with frequency increasing with the amount of antigens. Pain in the site of injection was the most frequent reaction in all doses, reported in more than the 85% across vaccine groups. Considering all injections, cephalea was the most common systemic adverse event, detected in 11.1%, 17.2% and 32.1%, respectively with doses of 12.5 μg, 25 μg and 50 μg. High titers of total IgG (ELISA) were observed for the vaccine components before vaccination. Protective levels of bactericidal antibodies (titer ≥1:4) for both vaccine strains were also present. Considering a 4-fold increase of IgG titers compared to pre-immune values (seroconversion), 50%-70% of those who received intermediate and highest doses of antigens presented satisfactory response for OMV of N44/89 strain. The lowest dose vaccine induced no seroconversion for strain N44/89, and 11% for strain N603/95. For the three vaccines doses, 25% of seroconversion, in total IgG against LOS, was observed. Increased antibody bactericidal activity was observed for both strains in higher antigen concentrations. For IgG against LOS, all vaccine formulations showed 25% of seroconversion. In conclusion, MenB-Bio experimental vaccines were well tolerated and immunogenic, thus allowing phase II studies., Competing Interests: Conflicts of interest At the time of the study, all authors, except LABC, were employed at Bio-Manguinhos/Fiocruz, a Brazilian state-owned producer of vaccines., (Copyright © 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: In 2018, meningococcal ACWY-TT vaccine (MenACWY-TT) was offered to adolescents in the Netherlands within the National Immunization Programme at 14 years of age. A questionnaire study assessed the tolerability of this vaccine., Methods: Five thousand adolescents were invited to participate and to fill in two questionnaires about systemic events in the week before vaccination and local reactions and systemic events in the week after vaccination. Frequencies of local and systemic adverse events in the week after vaccination were calculated. Association between the occurrence of systemic symptoms in the week before and after the vaccination was tested by using generalized mixed models (GLMM)., Results: Of all adolescents, 139 returned one or both questionnaires. Any local reaction within 7 days after vaccination was reported by 55.6% of the adolescents. Pain (50%) and reduced use of the injected arm (21.3%) were most often reported. Any systemic event was reported by 67.6% of the participants, with myalgia as the most often reported event (37.0%). Compared with the week before vaccination, there were no increased odds of experiencing systemic symptoms in the week after vaccination (OR 0.95; 95%CI 0.40-2.27)., Conclusions: After vaccination with MenACWY-TT vaccine, most adolescents reported one or more adverse events, which were mostly mild and transient. Systemic symptoms were not reported more often in the week after compared to the week before vaccination. Unfortunately, due to a low response rate we were not able to detect the absolute elevated risks the sample size calculation was based on. However, despite limited data, our results are in line with results from prelicensure data, and indicate that MenACWY-TT vaccination is well tolerated in adolescents., (© 2021. The Author(s).)

Background: Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public health threat in sub-Saharan Africa., Methods: We conducted a phase 3, double-blind trial in Blantyre, Malawi, to assess the efficacy of Vi polysaccharide typhoid conjugate vaccine (Vi-TCV). We randomly assigned children who were between 9 months and 12 years of age, in a 1:1 ratio, to receive a single dose of Vi-TCV or meningococcal capsular group A conjugate (MenA) vaccine. The primary outcome was typhoid fever confirmed by blood culture. We report vaccine efficacy and safety outcomes after 18 to 24 months of follow-up., Results: The intention-to-treat analysis included 28,130 children, of whom 14,069 were assigned to receive Vi-TCV and 14,061 were assigned to receive the MenA vaccine. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 cases per 100,000 person-years) and in 62 children in the MenA group (243.2 cases per 100,000 person-years). Overall, the efficacy of Vi-TCV was 80.7% (95% confidence interval [CI], 64.2 to 89.6) in the intention-to-treat analysis and 83.7% (95% CI, 68.1 to 91.6) in the per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in the Vi-TCV group and 78 in the MenA group), including 6 deaths (all in the MenA group). No serious adverse events were considered by the investigators to be related to vaccination., Conclusions: Among Malawian children 9 months to 12 years of age, administration of Vi-TCV resulted in a lower incidence of blood culture-confirmed typhoid fever than the MenA vaccine. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT03299426.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: To demonstrate extended protection against meningococcal serogroup B (MenB) disease after MenB-FHbp (bivalent rLP2086) vaccination, this study evaluated immunopersistence through 26 months following MenB-FHbp boosting after 2 or 3 primary doses in adolescents., Study Design: This phase 3, open-label study was an extension of 3 phase 2 studies with participants aged 11-18 years randomized to receive primary MenB-FHbp vaccination following 1 of 5 dosing schedules or control. A booster dose was administered 48 months after the primary series. Immunopersistence through 48 months after the last primary dose (persistence stage) and 26 months postbooster (booster stage) was determined by serum bactericidal assays using human complement (hSBAs) against 4 vaccine-heterologous test strains. Safety evaluations included adverse events (AEs) and local and systemic reactions., Results: Overall, 698 and 304 subjects enrolled in the persistence and booster stages, respectively. hSBA titers declined in all groups during 12 months postprimary vaccination, then remained stable through 48 months. One month postbooster, 93.4-100.0% of subjects achieved hSBA titers ≥ lower limit of quantitation against each test strain; percentages at 12 and 26 months postbooster were higher than at similar time points following primary vaccination. Primary and booster MenB-FHbp vaccinations were well tolerated, with ≤ 12.5% of subjects reporting AEs during each stage. The most common local (reported by 84.4-93.8% of subjects) and systemic (68.8-76.6%) reactions to the booster were injection site pain and fatigue and headache, respectively; ≤ 3.7% of subjects reported severe systemic events., Conclusion: Protective hSBA titers initially declined but were retained by many subjects for 4 years irrespective of primary MenB-FHbp vaccination schedule. Boosting at 48 months after primary vaccination was safe, well tolerated, and induced immune responses indicative of immunological memory that persisted through 26 months. Booster vaccination during late adolescence may prolong protection against MenB disease., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: [TV and LØ report grants from Pfizer Inc during the conduct of the study. SDS has no potential conflicts of interest to report. JB, SLH, and JP are current or previous employees of Pfizer Inc and may hold stock or stock options, have a patent US Patent 9561269 issued, and a patent US20150071959 pending. C-EF reports support from Pfizer provided to Skåne University Hospital for performing the study. All other authors are current employees of Pfizer Inc and may hold stock or stock options.]., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Neisseria meningitidis serogroups A, B, C, W, X, and Y cause outbreaks of meningococcal disease. Quadrivalent conjugate vaccines targeting the A, C, W, and Y serogroups are available. A pentavalent vaccine that also includes serogroup X (NmCV-5) is under development., Methods: We conducted a phase 2, observer-blinded, randomized, controlled trial involving Malian children 12 to 16 months of age. Participants were assigned in a 2:2:1 ratio to receive nonadjuvanted NmCV-5, alum-adjuvanted NmCV-5, or the quadrivalent vaccine MenACWY-D, administered intramuscularly in two doses 12 weeks apart. Participants were followed for safety for 169 days. Immunogenicity was assessed with an assay for serum bactericidal antibody (SBA) with rabbit complement on days 0, 28, 84, and 112., Results: A total of 376 participants underwent randomization, with 150 assigned to each NmCV-5 group and 76 to the MenACWY-D group; 362 participants received both doses of vaccine. A total of 1% of the participants in the nonadjuvanted NmCV-5 group, 1% of those in the adjuvanted NmCV-5 group, and 4% of those in the MenACWY-D group reported local solicited adverse events; 6%, 5%, and 7% of the participants, respectively, reported systemic solicited adverse events. An SBA titer of at least 128 was seen in 91 to 100% (for all five serotypes) of the participants in the NmCV-5 groups and in 36 to 99% (excluding serogroup X) of those in the MenACWY-D group at day 84 (before the second dose); the same threshold was met in 99 to 100% (for all five serotypes) of the participants in the NmCV-5 groups and in 92 to 100% (excluding serogroup X) of those in the MenACWY-D group at day 112. Immune responses to the nonadjuvanted and adjuvanted NmCV-5 formulations were similar., Conclusions: No safety concerns were identified with two doses of NmCV-5. A single dose of NmCV-5 elicited immune responses that were similar to those observed with two doses of MenACWY-D. Adjuvanted NmCV-5 provided no discernible benefit over nonadjuvanted NmCV-5. (Funded by the U.K. Foreign, Commonwealth, and Development Office; ClinicalTrials.gov number, NCT03295318.)., (Copyright © 2021 Massachusetts Medical Society.)

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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GCH received payment from IQVIA for the conduct of the current study, and payment for consultancy from the GSK group of companies outside the submitted work and has received funding for research and consultancy from a number of pharmaceutical and healthcare companies outside the submitted work. ID received payment from IQVIA for the conduct of the current study, and payment from the GSK group of companies outside the submitted work; PTH received indirect payment from Novartis, Novavax, Pfizer, and the GSK group of companies, outside the submitted work; PP received consulting fees from IQVIA for the current study, and Amgen, BMS, Novartis and the GSK group of companies, outside the submitted work; DR was employed by and held shares from the GSK group of companies; JK received payment from IQVIA for the conduct of the current study; VAK is employed by the GSK group of companies. All authors declare no other financial and non-financial relationships and activities., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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

Meningococcal serogroups A and C cause significant numbers of cases in China. The Sanofi Pasteur meningococcal polysaccharide A + C vaccine (Men-AC) was licensed in China in 1995. Immunogenicity and safety of a single dose of Men-AC against a similar marketed vaccine, the Lanzhou Institute serogroups A and C vaccine (Lanzhou-AC), were evaluated in children 2 to 6 y of age. Antibody titers were determined before and on Day 30 after vaccination using a serum bactericidal assay using baby rabbit complement (SBA-BR). Immunogenicity endpoints included rates of seroconversion (postvaccination antibody titers ≥4-fold higher) and seroprotection (postvaccination titers ≥1:8). Unsolicited systemic adverse events (AEs) within 30 minutes after vaccination, solicited injection site and systemic reactions between Days 0 and 7, unsolicited non-serious AEs within 30 d, and serious adverse events (SAEs) throughout were recorded. Seroconversion rates against serogroups A and C were 97.0% (95% confidence interval [CI], 94.5-98.6) and 94.7% (95% CI, 91.6-97.0), respectively, in the Men-AC group and 97.7% (95% CI, 95.4-99.1) and 94.8% (95% CI, 91.7-97.0), respectively, in the Lanzhou-AC group, while seroprotection rates were 98.0% (95% CI, 95.8-99.3) and 97.0% (95% CI, 94.5-98.6), respectively, in the Men-AC group and 99.0% (95% CI, 97.2-99.8) and 96.8% (95% CI, 94.1-98.4), respectively, in the Lanzhou-AC group. Non-inferiority of Men-AC with regard to immunogenicity was demonstrated since the lower bounds of the 95% CIs of the differences in rates between the two groups were > -5% for both serogroups. Both vaccines were well tolerated.

It is now over a decade since the meningococcal B vaccine, MeNZB, was in routine use in New Zealand. From July 2004 until June 2008 it was administered in a three-dose schedule to over a million individuals, aged six weeks to 20 years, to provide protection against the epidemic strain of group B Meningococci. The cost of the campaign, including the development of the vaccine was substantial, in excess of $200M, but it contributed to a reduced incidence of meningococcal infections along with a reduction in morbidity and mortality. The campaign led to the development of a national immunisation register (NIR), which is still in existence today. As well as considering the legacies of the MeNZB vaccination programme, this paper examines whether there are any lessons to be learned, specifically concerning active vaccine safety monitoring, which may be important if, and when, a COVID-19 vaccine is developed and a national immunisation campaign instituted., Competing Interests: Nil.

Background: Better understanding of vaccine reactogenicity is crucial given its potential impact upon vaccine safety and acceptance. Here we report a comparison between conventional and novel (continuous) methods of monitoring temperature and evaluate any association between reactogenicity and the monocyte activation test (MAT) employed for testing four-component capsular group B meningococcal vaccine (4CMenB) batches prior to release for clinical use in Europe., Methods: Healthy 7-12-week-old infants were randomised in two groups: group PCV13 2 + 1 (received pneumococcal conjugate vaccine 13 valent (PCV13) at 2, 4 and 12 months) and group PCV13 1 + 1 (received reduced schedule at 3 and 12 months). In both, infants received the remaining immunisations as per UK national schedule (including 4CMenB at 2, 4 and 12 months of age). Fever was measured for the first 24 h after immunisations using an axillary thermometer and with a wireless continuous temperature monitoring device (iButton®). To measure the relative pyrogenicity of individual 4CMenB batches, MAT was performed according to Ph. Eu. chapter 2.6.30 method C using PBMCs with IL-6 readout., Results: Fever rates detected by the iButton® ranged from 28.7% to 76.5% and from 46.6% to 71.1% in group PCV13 2 + 1 and PCV13 1 + 1 respectively, across all study visits. The iButton® recorded a higher number of fever episodes when compared with axillary measurements in both groups (range of axillary temperature fevers; group PCV13 2 + 1: 6.7%-38%; group PCV13 1 + 1: 11.4%-37.1%). An agreement between the two methods was between 0.39 and 0.36 (p < 0.001) at 8 h' time-point post primary immunisations. No correlation was found between MAT scores and fever rates, or other reported adverse events., Conclusions: It is likely that conventional, intermittent, fever measurements underestimates fever rates following immunisation. 4CMenB MAT scores didn't predict reactogenicity, providing reassurance that vaccine batches with the highest acceptable pyrogen level are not associated with an increase in adverse events. Clinicaltrials.gov identifier: NCT02482636., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [MVP is a member of the Portuguese National Immunisation Technical Advisory Group - (Comissão Técnica de Vacinação da Direcção Geral de Saúde). MDS acts on behalf of the University of Oxford and Oxford Vaccine Group (OVG) as Chief or Principal Investigator on clinical trials sponsored and/or funded by vaccine manufacturers including Pfizer and GSK and JP, MVP, and EP are employed by the OVG. DG has served on ad-hoc advisory boards for GSK, Merck and Sano and is a National Institute of Health Research (NIHR) Senior Investigator. The UCL GOSICH Lab (DG) has received contract research funding from GSK, Merck and Sano. RB performs contract research on behalf of Public Health England for GSK, Pfizer and Sanofi Pasteur. KD, JS, NJA, and EM declare no competing interests.]., (Copyright © 2020. Published by Elsevier Ltd.)

Neisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. Here we describe the blood transcriptome and proteome following infant immunisations with or without concomitant 4CMenB, to gain insight into the molecular mechanisms underlying post-vaccination reactogenicity and immunogenicity. Infants were randomised to receive control immunisations (PCV13 and DTaP-IPV-Hib) with or without 4CMenB at 2 and 4 months of age. Blood gene expression and plasma proteins were measured prior to, then 4 h, 24 h, 3 days or 7 days post-vaccination. 4CMenB vaccination was associated with increased expression of ENTPD7 and increased concentrations of 4 plasma proteins: CRP, G-CSF, IL-1RA and IL-6. Post-vaccination fever was associated with increased expression of SELL, involved in neutrophil recruitment. A murine model dissecting the vaccine components found the concomitant regimen to be associated with increased gene perturbation compared with 4CMenB vaccine alone with enhancement of pathways such as interleukin-3, -5 and GM-CSF signalling. Finally, we present transcriptomic profiles predictive of immunological and febrile responses following 4CMenB vaccine., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

This study is aimed to review the published evidence on safety, immunogenicity, and efficacy of rotavirus vaccines when co-administered with meningococcal vaccines in infants. A systematic literature search was performed in four databases containing peer-reviewed articles and conference abstracts. In total, twelve articles were included in the review; 11 provided information on safety and five on the immunogenicity of rotavirus vaccines following co-administration. No paper was found on efficacy. Additional routine vaccines were administered in all studies. The safety analysis was mainly focused on fever, vomiting, diarrhea, intussusception, and changes in eating habits. Overall, safety profiles and immune responses associated with rotavirus vaccination were comparable between infants co-administered with rotavirus and meningococcal vaccines and infants receiving rotavirus vaccines without meningococcal vaccines. Although data are limited, co-administration of rotavirus and meningococcal vaccines does not appear to interfere with the safety or immunogenicity of rotavirus vaccines.

Background: Post marketing safety evaluations of quadrivalent meningococcal diphtheria-toxoid conjugate vaccine (MenACWY-D) have focused on post-vaccination risk of Guillain Barré syndrome (GBS), adverse events (AEs) after maternal vaccination, and comparative studies with the newer quadrivalent meningococcal CRM 197 conjugate vaccine (MenACWY-CRM). To provide an updated general safety assessment, we reviewed reports of AEs following MenACWY-D submitted to the Vaccine Adverse Event Reporting System (VAERS)., Methods: VAERS is a national spontaneous reporting vaccine safety surveillance system co-administered by the Centers for Disease Control and Prevention and the U.S. Food and Drug Administration. We searched the VAERS database for U.S. reports of AEs after administration of MenACWY-D from January 2005 through June 2016. We conducted clinical reviews of serious reports after MenACWY-D administered alone, reports of MenACWY-D use during pregnancy, and reports of selected pre-specified outcomes. We screened for disproportionate reporting of AEs after MenACWY-D using empirical Bayesian data mining., Results: VAERS received 13,075 U.S. reports after receipt of MenACWY-D; most (86%) described vaccination in adolescents, were classified as non-serious (94%), and described AEs consistent with pre-licensure studies. We did not find any evidence that reported deaths were related to vaccination. In serious reports, GBS and meningococcal infection were the most commonly reported medical conditions. Many reports of MenACWY-D use during pregnancy described inadvertent vaccination; most (61%) did not report any AE., Conclusions: Findings from our comprehensive review of reports to VAERS following MenACWY-D are consistent with data from pre-licensure studies and provide further reassurance on the safety of MenACWY-D., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Objective: The aim of this study was to evaluate the safety and immunogenicity of the first domestic ACYW135 meningococcal conjugate vaccine and a control vaccine named AC group meningococcal conjugate vaccine for 3 months (90-119 days) infants. Methods: From February 2017 to June 2018, a randomized, blinded, and similar vaccine-controlled clinical trial design was adopted at the Henan Vaccine Clinical Research Base. The subjects were 3 months old healthy infants, a total of 720, based on a 1∶1 ratio. The random allocation table for entry was randomly assigned to the experimental group and the control group. According to the 3, 4, and 5 month-old vaccination procedures, the subjects were vaccinated with test vaccine (ACYW135 group meningococcal conjugate vaccine) and control vaccine (group A group C meningococcal polysaccharide conjugate vaccine), of which 720 were given the first dose, 696 were given the second dose (test group: 346; control group: 350), and 692 were given the third dose (test group: 344; Control group: 348). Results: The overall adverse reaction rate of the test vaccine was 21.90% (230 cases), which was lower than the 32.04% (339 cases) of the control vaccine ( P <0.001). The incidence of systemic adverse reactions was 19.52% (205 cases), which was lower than that of the control vaccine (27.69%) (293 cases) ( P <0.001). The local adverse reaction rate was 3.04% (32 cases), which was lower than the control group (7.84%) (83 cases) ( P <0.001). The graded adverse reaction test vaccine was 0.57% (6 cases), which was lower than the control group of 2.36% (25 cases) ( P <0.001). The positive conversion rate of anti-bacterial serum antibodies showed that there was no significant difference between the test vaccine group A (91.42%), C (88.76%) and the control vaccine (92.92%) (87.02%) ( P >0.05). Group Y and W135 was 88.17% (298 cases), 99.41% (336 cases), respectively. The GMT results showed that the test vaccine group A was 56.24, the control vaccine was 57.43 ( P >0.05); the group C test vaccine (43.53) was higher than the control group (27.28) ( P <0.001). The group Y and W135 are 89.22 and 140.66, respectively. Among them, the proportion of the group C GMT antibody ≥ 1∶128 for test vaccine (31.07%, 105 cases) was higher than the control vaccine (16.22%, 55 cases) ( P <0.001). Conclusion: ACYW135 group meningococcal conjugate vaccine has more safety and immunogenicity after application to 3 month old infants.

Background: Four-component meningococcal B (4CMenB) vaccine is licensed in many countries but has had limited use in adolescents despite this age group being at increased risk of meningococcal disease., Objectives: To assess the safety profile of two doses of 4CMenB in adolescents., Methods: Cluster randomised controlled trial of senior school students in South Australia (SA) with participating schools randomised to intervention (4CMenB) or control. Vaccine safety was monitored using the South Australian Vaccine Safety Surveillance System (SAVSS), a spontaneous reporting system for adverse events following immunisation (AEFI) with enhanced follow-up of AEFI., Results: 58,637 doses of 4CMenB vaccine were administered to 30,522 students (median age 16 years) during 2017-2018. Of 18,348 and 12,174 students vaccinated in 2017 and 2018, 97.3% and 84.3%, respectively, received both scheduled doses (N = 28,115). 193 AEFI in 187 students were reported with a reporting rate of 0.32% (95%CI: 0.28-0.39%). Seventy individuals sought medical review, including nine serious adverse events. 98% (166/169) of those who were contactable for AEFI follow-up (87.6% 169/193) reported resolution of the event. Most common AEFI were injection site reaction (126/193), headache (99/193) and nausea (61/193). AEFI were more frequently reported in females (aOR = 1.409 (95%CI: 1.002, 1.980)), schools with high level of educational advantage (adjusted Odds Ratio (aOR) = 1.515 (95%CI: 1.005, 2.284)), following first dose (aOR = 1.619 (95%CI: 1.168, 2.244)), and in 2017 (aOR = 1.437 (95%CI: 1.001, 2.064)). Reported AEFI declined with increasing age (aOR = 0.771 (95%CI: 0.673, 0.883))., Conclusion: In this largest post-licensure use of 4CMenB in adolescents, the low AEFI reporting rate provides real-world evidence of 4CMenB safety in this age group. (ClinicalTrials.gov number: NCT03089086)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “HM is an investigator on clinical trials of investigational vaccines sponsored by Industry. Her institution receives funding from Industry (GSK, Pfizer, Sanofi-Pasteur) for Investigator led research and for sponsored studies (Novavax). She does not receive any personal payments from Industry. Other authors report no conflict”., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Meningococcal disease remains one of the most feared infectious diseases worldwide because of its sudden onset, rapid progression and high case fatality rates, while survivors are often left with severe long-term sequelae. Young children have the highest incidence of invasive meningococcal disease (IMD), and nearly all cases in the UK, as in most of Europe and many other industrialised countries, are due to group B meningococci (MenB). The licensure of a broad-coverage, recombinant protein-based MenB vaccine (4CMenB) in 2013 was, therefore, heralded a major breakthrough in the fight against IMD. This vaccine was, however, licensed on immunogenicity and reactogenicity studies only, raising uncertainties about field effectiveness, long-term safety and antibody persistence. In 2015, the UK became the first country to implement 4CMenB into the national infant immunisation schedule and, since then, several countries have followed suit. Seven years after licensure, a wealth of real-world data has emerged to confirm 4CMenB effectiveness, along with large-scale safety data, duration of protection in different age groups, successful strategies to reduce vaccine reactogenicity, impact on carriage in adolescents and the potential for 4CMenB to protect against other meningococcal serogroups and against gonorrhoea. A number of questions, however, remain unanswered, including the investigation and management of vaccine-associated fever in infants, as well as disease severity and assessment of breakthrough cases in immunised children. Increasing use of 4CMenB will provide answers in due course. We now have vaccines against all the major serogroups causing IMD worldwide. Next-generation and combination vaccines against multiple serogroups look very promising., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MSD, JP, DN, and EJ are employees of Sanofi Pasteur. JP reports personal fees from Sanofi Pasteur, during the conduct of the study. JH has nothing to disclose., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Invasive meningococcal disease has a high mortality rate in individuals aged ≥56 years, but no vaccine is currently licensed in the USA for this age group. This study assessed the safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) compared with a meningococcal quadrivalent polysaccharide vaccine (MPSV4) in this age group., Methods: This was a Phase III, modified double-blind, randomized, non-inferiority study (NCT02842866) across 35 clinical sites in the USA and Puerto Rico in individuals aged ≥56 years. A single dose of the MenACYW-TT (n = 451) or MPSV4 vaccine (n = 455) was administered on Day 0. A serum bactericidal assay with human (hSBA) and baby rabbit (rSBA) complement was used to measure antibodies against serogroups A, C, W, and Y test strains at baseline and Day 30. Safety data were collected up to six months post-vaccination., Results: The seroresponse to MenACYW-TT was non-inferior to MPSV4 for each of the serogroups (A: 58.2% vs. 42.5%; C: 77.1% vs. 49.7%; W: 62.6% vs. 44.8%, Y: 74.4% vs. 43.4%, respectively). At Day 30, participants achieving hSBA titers ≥1:8 were higher for all serogroups after MenACYW-TT vs. MPSV4 (77.4-91.7 vs. 63.1-84.2%, respectively). No safety concerns were identified for either vaccine., Conclusion: MenACYW-TT was well-tolerated and immunogenic in ≥56-year-olds, offering the potential to replace MPSV4 in this age group., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AEJ, DN, EJ, and MSD are employees of Sanofi Pasteur. MSD and EJ hold stock options for Sanofi Pasteur. TK is an employee of Heartland Research Associates which was under contract to Sanofi Pasteur to conduct this research, and RJ is an employee of MedPharmics which was under contract to Sanofi Pasteur to conduct this research., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The quadrivalent meningococcal conjugate vaccine MenACWY-CRM is approved in the Republic of Korea for use in individuals from 2 months of age. This single-arm, open-label, observational, multicenter, post-marketing study (NCT01766206) assessed the safety of MenACWY-CRM vaccine administered according to local clinical practice. A total of 3939 individuals aged 2 months-55 years provided safety data post-vaccination; the analysis was conducted on the per-protocol set (3920 participants). Solicited and unsolicited adverse events (AEs) were collected over 7 days post-vaccination and medically-attended AEs (MAAEs) and serious AEs (SAEs) over 29 days post-vaccination. Among recorded solicited AEs, injection site AEs were reported by 21.38% of participants, with tenderness/pain being most frequent across age groups; systemic AEs were reported in 13.95% of participants, with irritability (in ˂6-year-olds), headache and myalgia (in ≥6 year-olds) being the most frequently reported. Most solicited AEs were mild or moderate in nature. The percentage of participants reporting unsolicited AEs varied in the study population, i.e. 12.56% in participants aged 2-23 months and 3.18% in those ≥2 years of age. Overall, less than 22% of unsolicited AEs were considered as related to vaccination. MAAEs (10.89% of participants) were mostly mild; 2.82% were considered as related to vaccination. Three (0.46%) and 5 (0.15%) SAEs (none vaccination-related) occurred in participants aged 2-23 months and 2-55 years, respectively. No deaths were reported. The safety profile for MenACWY-CRM in this post-marketing surveillance was consistent with observations from studies conducted during the vaccine's clinical development, with no new safety concerns.