Meningococcal polysaccharide A, C, W135 and Y conjugate vaccine powder and solvent for solution for injection 0.5ml vials

BackgroundVaccine supply shortages are of global concern. We hypothesise that intradermal (ID) immunisation as an alternative to standard routes might augment vaccine supply utilisation without loss of vaccine immunogenicity and efficacy.MethodsWe conducted a systematic review and meta-analysis searching Medline, Embase and Web of Science databases. Studies were included if: licensed, currently available vaccines were used; fractional dose of ID was compared to IM or SC immunisation; primary immunisation schedules were evaluated; immunogenicity, safety data and/or cost were reported. We calculated risk differences (RD). Studies were included in meta-analysis if: a pre-defined immune correlate of protection was assessed; WHO-recommend schedules and antigen doses were used in the control group; the same schedule was applied to both ID and control groups (PROSPERO registration no. CRD42020151725).ResultsThe primary search yielded 5,873 articles, of which 156 articles were included; covering 12 vaccines. Non-inferiority of immunogenicity with 20-60% of antigen used with ID vaccines was demonstrated for influenza (H1N1: RD -0·01; 95% CI -0·02, 0·01; I2 = 55%, H2N3: RD 0·00; 95% CI -0·01, 0·01; I2 = 0%, B: RD -0·00; 95% CI -0·02, 0·01; I2 = 72%), rabies (RD 0·00; 95% CI -0·02, 0·02; I2 = 0%), and hepatitis B vaccines (RD -0·01; 95% CI -0·04, 0·02; I2 = 20%). Clinical trials on the remaining vaccines yielded promising results, but are scarce.ConclusionsThere is potential for inoculum/antigen dose-reduction by using ID immunisation as compared to standard routes of administration for some vaccines (e.g. influenza, rabies). When suitable, vaccine trials should include an ID arm.

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BackgroundMeningococcal disease is caused by the bacteria Neisseria meningitidis, leading to substantial mortality and severe morbidity; with serogroups A, B, C, W135, X and Y most significant in causing disease. An outbreak is defined as multiple cases of the same serogroup occurring in a population over a short time-period. A systematic review was performed to gain insight into outbreaks of meningococcal disease and to describe the temporal pattern over the last 50 years in non-African countries.MethodsPubMed and EMBASE were searched for English-language publications on outbreaks of meningococcal disease in non-African countries between January 1966 and July 2017, with an additional grey literature search. Articles and reports were considered eligible if they reported confirmed meningococcal outbreak cases, included the region, number of cases, and the start and end dates of the outbreak. Data on outbreaks was stratified by geographical region in accordance with the World Health Organization (WHO) regional classification, and case-fatality rates (CFRs) were calculated.ResultsOf the identified publications, 3067 were screened and 73 included, reporting data from 83 outbreaks. The majority of outbreaks were identified in the regions of the Americas (41/83 outbreaks), followed by the European region (30/83 outbreaks). In each of the Western Pacific, Eastern Mediterranean, and South-East Asian regions there were ConclusionsThese data present a retrospective view of the patterns for meningococcal disease outbreaks in non-African countries, and provide valuable data for monitoring future changes in disease epidemiology and informing preventive measures.

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IntroductionNeisseria meningitidis (Nm) is a major cause of meningitis and septicemia. Most people are infected with latent infections or are carriers. We aimed to estimate the carriage prevalence of Nm in China.MethodsWe did a systematic review of published work to assess the prevalence of meningococcal carriage in China. The quality assessment was conducted by the risk of bias tool according to Damian Hoy's study. We estimated pooled proportions of carriage and its 95% confidence interval (95% CI) using fixed effect model for studies with low heterogeneity and random effect model for studies with moderate or high heterogeneity. Subgroup analyses were also conducted by region and age group.ResultsIn total, 115 studies were included. The quality evaluation grades of all included documents were medium or high grade. The weighted proportion of carriage was 2.86% (95% CI: 2.25-3.47%, I2: 97.7%, p = 0). The carriage prevalence of Nm varied between provinces, ranged from 0.00% (95% CI: 0.00-0.66%) to 15.50% (95% CI: 14.01-16.99%). Persons aged 15 years and older had the highest carriage 4.38% (95% CI: 3.15-5.62%, I2: 95.4%, p 2: 98.6%, p = 0) took up the highest proportion, and serogroup X (0.02%, 95% CI: 0.00-0.09%, I2: 0.00%, p = 1) accounted for the lowest proportion.ConclusionThe meningococcal carriage in China was estimated low and varied by region and age group. Understanding the epidemiology and transmission dynamics of meningococcal infection in insidious spreaders is essential for optimizing the meningococcal immunization strategies of the country.

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ObjectiveTo perform systematic review and meta-analysis of meningococcal disease burden in India.MethodsWe searched publications on meningococcal disease in India between 1996 and 2020 using PubMed and Google Scholar. Prevalence (proportion) of Meningococcal meningitis and Case-fatality ratio (CFR) were pooled using random effects model. Other outcomes were pooled qualitatively.ResultsThe prevalence of Meningococcal meningitis in epidemic and endemic conditions was 12.1% (95% CI: 5.2-21.4) and 0.76% (95% CI: 0.3-1.4), respectively, with a CFR of 12.8% (95% CI: 6.8-20.4) in epidemic settings; N. meningitis caused 3.2% (95% CI: 1.6-5.3) of Acute Bacterial Meningitis (ABM) cases in endemic settings. The disease appeared in infants, adolescents, and adults with Serogroup A prevalence. Treatment and prophylaxis were limited to antibiotics despite increased resistance.ConclusionThe study reveals epidemic and endemic presence of the disease in India with high fatality and serogroup A prevalence. Further monitoring and immunization are required to prevent outbreaks.

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BackgroundInvasive meningococcal disease (IMD) represents a global health burden. However, its epidemiology in the Eastern Mediterranean (EM) and North Africa (NA) regions is currently not well understood. This review had four key objectives: to describe asymptomatic meningococcal carriage, IMD epidemiology (e.g. serogroup prevalence, case-fatality rates [CFRs]), IMD presentation and management (e.g. clinical diagnosis, antibiotic treatments) and economic impact and evaluation (including health technology assessment [HTA] recommendations) in EM and NA.MethodsA systematic literature search (MEDLINE and EMBASE) was conducted (January 2000 to February 2021). Search strings included meningococcal disease and the regions/countries of interest. Identified publications were screened sequentially by title/abstract, followed by screening of the full-text article; articles were also assessed on methodological quality. Literature reviews, genetic sequencing or diagnostic accuracy studies, or other non-pertinent publication type were excluded. An additional grey literature search (non-peer-reviewed sources; start date January 2000) was conducted to the end of April 2019.ResultsOf the 1745 publications identified, 79 were eligible for the final analysis (n = 61 for EM and n = 19 for NA; one study was relevant to both). Asymptomatic meningococcal carriage rates were 0-33% in risk groups (e.g. military personnel, pilgrims) in EM (no data in NA). In terms of epidemiology, serogroups A, B and W were most prevalent in EM compared with serogroups B and C in NA. IMD incidence was 0-20.5/100,000 in EM and 0.1-3.75/100,000 in NA (reported by 7/15 countries in EM and 3/5 countries in NA). CFRs were heterogenous across the EM, ranging from 0 to 57.9%, but were generally lower than 50%. Limited NA data showed a CFR of 0-50%. Data were also limited in terms of IMD presentation and management, particularly relating to clinical diagnosis/antibiotic treatment. No economic evaluation or HTA studies were found.ConclusionsHigh-risk groups remain a significant reservoir of asymptomatic meningococcal carriage. It is probable that inadequacies in national surveillance systems have contributed to the gaps identified. There is consequently a pressing need to improve national surveillance systems in order to estimate the true burden of IMD and guide appropriate prevention and control programmes in these regions.

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Neisseria gonorrhoeae (gonococcus) and Neisseria meningitidis (meningococcus) are important global pathogens which cause the sexually transmitted diseases gonorrhea and meningitis, respectively, as well as sepsis. We prepared a review according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA), with the aims of (a) evaluating the data on the MenB vaccination as protection against sexually transmitted infections by N. gonorrhoeae and (b) to briefly comment on the data of ongoing studies of new vaccines. We evaluated existing evidence on the effect of 4CMenB, a multi-component vaccine, on invasive diseases caused by different meningococcal serogroups and on gonorrhea. Non-B meningococcal serogroups showed that the 4CMenB vaccine could potentially offer some level of protection against non-B meningococcal serogroups and N. gonorrhoeae. The assessment of the potential protection conferred by 4CMenB is further challenged by the fact that further studies are still needed to fully understand natural immune responses against gonococcal infections. A further limitation could be the potential differences between the protection mechanisms against N. gonorrhoeae, which causes local infections, and the protection mechanisms against N. meningitidis, which causes systemic infections.

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This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of meningococcal vaccines in the United States. As a comprehensive summary and update of previously published recommendations, it replaces all previously published reports and policy notes. This report also contains new recommendations for administration of booster doses of serogroup B meningococcal (MenB) vaccine for persons at increased risk for serogroup B meningococcal disease. These guidelines will be updated as needed on the basis of availability of new data or licensure of new meningococcal vaccines. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination with MenACWY for persons aged ≥2 months at increased risk for meningococcal disease caused by serogroups A, C, W, or Y, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor (e.g., eculizumab [Soliris] or ravulizumab [Ultomiris]); persons who have anatomic or functional asplenia; persons with human immunodeficiency virus infection; microbiologists routinely exposed to isolates of Neisseria meningitidis; persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroups A, C, W, or Y; persons who travel to or live in areas in which meningococcal disease is hyperendemic or epidemic; unvaccinated or incompletely vaccinated first-year college students living in residence halls; and military recruits. ACIP recommends MenACWY booster doses for previously vaccinated persons who become or remain at increased risk.In addition, ACIP recommends routine use of MenB vaccine series among persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor; persons who have anatomic or functional asplenia; microbiologists who are routinely exposed to isolates of N. meningitidis; and persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroup B. ACIP recommends MenB booster doses for previously vaccinated persons who become or remain at increased risk. In addition, ACIP recommends a MenB series for adolescents and young adults aged 16-23 years on the basis of shared clinical decision-making to provide short-term protection against disease caused by most strains of serogroup B N. meningitidis.

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BackgroundChildren account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone.MethodsThis randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1-17 years were enrolled in three age cohorts (12-17 years, 4-11 years, and 1-3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494.FindingsFrom April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1-3 years after placebo injection to 21% (30 of 144) of children aged 4-11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12-17 years and 4-11 years age cohorts after the first and second dose, and pyrexia in the 1-3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12-17 years (9929 ELISA units [EU]/mL [95% CI 8172-12 064]), in 119 (99%) of 120 aged 4-11 years (10 212 EU/mL [8419-12 388]), and in 118 (98%) of 121 aged 1-3 years (22 568 EU/mL [18 426-27 642]).InterpretationThe Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1-17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children.FundingInnovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.

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