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Adverse events following immunisation with four-component meningococcal serogroup B vaccine (4CMenB): interaction with co-administration of routine infant vaccines and risk of recurrence in European randomised controlled trials.

ABSTRACT: OBJECTIVES:(1) To assess if co-administration of four-component meningococcal serogroup B vaccine (4CMenB) and other routine vaccines caused an interaction increasing the risk and/or severity of adverse events following immunisation (AEFI) compared with administration at separate visits and (2) to estimate the risk of AEFI recurrence. DESIGN:Risk-interval design SETTING: Three randomised controlled trials conducted in Europe. PARTICIPANTS:A total of 5026 healthy 2-month-old to 15-month-old infants. INTERVENTIONS:4CMenB and routine vaccines (hexavalent combined diphtheria-tetanus-acellular pertussis-inactivated polio-Haemophilus influenzae type b-hepatitis B vaccine+seven-valent pneumococcal conjugate vaccine or measles-mumps-rubella-varicella vaccine) administered concomitantly or separately 1?month apart, in regular (2, 4, 6 and 12 months), accelerated (2, 3, 4 and 12 months) or delayed (two doses of 4CMenB at ?12 months of age) schedules. OUTCOME MEASURES:Primary: Fever (?38°C) during the first 48?hours post immunisation. Secondary: crying, change in eating habits, diarrhoea, irritability and tenderness at the 4CMenB injection site. RESULTS:Compared with separate administration, concomitant administration decreased the overall incidence of fever (?38°C), 86% versus 75%, and other systemic AEFIs but increased the incidence of 4CMenB injection site tenderness, 55% versus 66%, moderate/severe fevers (?39°C), 13% versus 18%, and long-lasting (>1?day) fevers, 23% versus 33%. Co-administration reduced AEFI risk by 4%-49% with the greatest impact among infants with prior AEFI(s). Fever recurrence risk was proportional to the number of prior fever events: 79% at dose 2 with one prior episode; 44% and 74% at dose 3 with one and two prior episodes, respectively; and 29%, 45% and 60% at dose 4 with one, two and three prior episodes, respectively. Severity was not increased at recurrence and a similar pattern of recurrence risk proportional to the number of prior events was observed for other AEFIs. CONCLUSIONS:The cumulative risk of AEFI is reduced with concomitant versus separate administration of 4CMenB and routine infant vaccines. Infants with a prior AEFI are at higher risk of the same AEFI at subsequent immunisations, but severity with recurrence is usually not increased. TRIALS REGISTRATION NUMBER:NCT00657709, NCT00847145, NCT00721396 and NCT02712177; Pre-results.

SUBMITTER: Zafack JG

PROVIDER: S-EPMC6530311 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Adverse events following immunisation with four-component meningococcal serogroup B vaccine (4CMenB): interaction with co-administration of routine infant vaccines and risk of recurrence in European randomised controlled trials.

Zafack Joseline Guetsop JG Bureau Alexandre A Skowronski Danuta M DM De Serres Gaston G

BMJ open 20190519 5

<h4>Objectives</h4>(1) To assess if co-administration of four-component meningococcal serogroup B vaccine (4CMenB) and other routine vaccines caused an interaction increasing the risk and/or severity of adverse events following immunisation (AEFI) compared with administration at separate visits and (2) to estimate the risk of AEFI recurrence.<h4>Design</h4>Risk-interval design SETTING: Three randomised controlled trials conducted in Europe.<h4>Participants</h4>A total of 5026 healthy 2-month-old ...[more]

PMID: 31110098

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

Project description:There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance in Neisseria gonorrhoeae (Ng). Current gonorrhea vaccine research is in the stages of antigen discovery and the identification of protective immune responses, and no vaccine has been tested in clinical trials in over 30 years. Recently, however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B Neisseria meningitidis (Nm) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea. Here we directly tested the hypothesis that Nm OMVs induce cross-protection against gonorrhea in a well-characterized female mouse model of Ng genital tract infection. We found that immunization with the licensed Nm OMV-based vaccine 4CMenB (Bexsero) significantly accelerated clearance and reduced the Ng bacterial burden compared to administration of alum or PBS. Serum IgG and vaginal IgA and IgG that cross-reacted with Ng OMVs were induced by 4CMenB vaccination by either the subcutaneous or intraperitoneal routes. Antibodies from vaccinated mice recognized several Ng surface proteins, including PilQ, BamA, MtrE, NHBA (known to be recognized by humans), PorB, and Opa. Immune sera from both mice and humans recognized Ng PilQ and several proteins of similar apparent molecular weight, but MtrE was only recognized by mouse serum. Pooled sera from 4CMenB-immunized mice showed a 4-fold increase in serum bactericidal50 titers against the challenge strain; in contrast, no significant difference in bactericidal activity was detected when sera from 4CMenB-immunized and unimmunized subjects were compared. Our findings directly support epidemiological evidence that Nm OMVs confer cross-species protection against gonorrhea, and implicate several Ng surface antigens as potentially protective targets. Additionally, this study further defines the usefulness of murine infection model as a relevant experimental system for gonorrhea vaccine development.

Dataset Information

Adverse events following immunisation with four-component meningococcal serogroup B vaccine (4CMenB): interaction with co-administration of routine infant vaccines and risk of recurrence in European randomised controlled trials.

Publications

Adverse events following immunisation with four-component meningococcal serogroup B vaccine (4CMenB): interaction with co-administration of routine infant vaccines and risk of recurrence in European randomised controlled trials.

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