BACKGROUND The meningococcal group B vaccine 4CMenB is a new, recombinant protein-based vaccine that is licensed to protect against invasive group B meningococcal disease. However, its role in preventing transmission and, therefore, inducing population (herd) protection is uncertain. METHODS We used cluster randomization to assign, according to school, students in years 10 to 12 (age, 15 to 18 years) in South Australia to receive 4CMenB vaccination either at baseline (intervention) or at 12 months (control). The primary outcome was oropharyngeal carriage of disease-causing Neisseria meningitidis (group A, B, C, W, X, or Y) in students in years 10 and 11, as identified by polymerase-chain-reaction assays for PorA (encoding porin protein A) and N. meningitidis genogroups. Secondary outcomes included carriage prevalence and acquisition of all N. meningitidis and individual disease-causing genogroups. Risk factors for carriage were assessed at baseline. RESULTS A total of 237 schools participated. During April through June 2017, a total of 24,269 students in years 10 and 11 and 10,220 students in year 12 were enrolled. At 12 months, there was no difference in the prevalence of carriage of disease-causing N. meningitidis between the vaccination group (2.55%; 326 of 12,746) and the control group (2.52%; 291 of 11,523) (adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.80 to 1.31; P = 0.85). There were no significant differences in the secondary carriage outcomes. At baseline, the risk factors for carriage of disease-causing N. meningitidis included later year of schooling (adjusted odds ratio for year 12 vs. year 10, 2.75; 95% CI, 2.03 to 3.73), current upper respiratory tract infection (adjusted odds ratio, 1.35; 95% CI, 1.12 to 1.63), cigarette smoking (adjusted odds ratio, 1.91; 95% CI, 1.29 to 2.83), water-pipe smoking (adjusted odds ratio, 1.82; 95% CI, 1.30 to 2.54), attending pubs or clubs (adjusted odds ratio, 1.54; 95% CI, 1.28 to 1.86), and intimate kissing (adjusted odds ratio, 1.65; 95% CI, 1.33 to 2.05). No vaccine safety concerns were identified. CONCLUSIONS Among Australian adolescents, the 4CMenB vaccine had no discernible effect on the carriage of disease-causing meningococci, including group B. (Funded by GlaxoSmith-Kline; ClinicalTrials.gov number, NCT03089086.

Introduction: Neisseria meningitidis serogroup B (MenB) is the most common cause of bacterial meningitis in many industrialized countries and occurs at any age. The highest incidence is in infants aged <1 year, followed by children and adolescents. Four-component MenB vaccine (4CMenB, Bexsero) is the only MenB vaccine authorized for use in all age-groups. Experience with 4CMenB is growing as it is implemented in different countries/age-groups encompassing university students, children, adolescents, and infant mass vaccination programs. Areas covered: An update of recently available data describing the mechanism of immunogenicity of 4CMenB and real-world evidence of vaccine effectiveness and disease impact. We discuss the appropriate age for vaccination to maximize population impacts. Expert commentary: Invasive meningococcal disease is uncommon and sufficiently powered efficacy studies were not feasible during 4CMenB development. Additionally, several thousand genetically diverse invasive MenB strains circulate globally, varying widely in surface protein expression. This posed significant challenges in predicting clinical protection with MenB vaccines. Five years of 4CMenB use post-licensure confirm the clinical benefit of vaccination as predicted during development. Preliminary evidence suggests an extended impact on other meningococcal serogroups and Neisseria gonorrhoeae.

IntroductionSouth Australia (SA) has the highest notification rate of invasive meningococcal disease in Australia with the majority of cases due to serogroup B. Neisseria meningitidis is carried in the pharynx, with adolescents having the highest rates of carriage. A vaccine designed to offer protection against serogroup B (4CMenB) is licensed in Australia. The SA MenB vaccine carriage study aims to assess the impact of 4CMenB on carriage of N. meningitidis in adolescents.Methods and analysisThis is a parallel cluster randomised controlled trial enrolling year 10, 11 and 12 school students (approximately 16–18 years of age) throughout SA, in metropolitan and rural/remote areas. Schools are randomised to intervention (4CMenB vaccination at baseline) or control (4CMenB vaccination at study completion) with randomisation stratified by school size and socioeconomic status, as measured by the Index of Community Socio-Educational Advantage (Australian Curriculum). Oropharyngeal swabs will be taken from all students at visit 1, and 12 months later from year 11 and 12 students. Students unvaccinated in 2017 will receive vaccine at the 12-month follow-up. Carriage prevalence of N. meningitidis will be determined by PCR at baseline and 12 months following 4CMenB vaccination and compared with carriage prevalence at 12 months in unvaccinated students. A questionnaire will be completed at baseline and 12 months to assess risk factors associated with carriage. The primary outcome of carriage prevalence of disease causing N. meningitidis at 12 months will be compared between groups using logistic regression, with generalised estimating equations used to account for clustering at the school level. The difference in carriage prevalence between groups will be expressed as an OR with 95% CI.Ethics and disseminationThe study was approved by the Women’s and Children’s Health Network Human Research Ethics Committee (WCHN HREC). The protocol, informed consent forms, recruitment materials, social media and all participant materials have been reviewed and approved by the WCHN HREC and updated on ClinicalTrials.gov. Results will be published in international peer-reviewed journals and presented at national and international conferences. The study findings will be provided in public forums and to study participants and participating schools.Trial registration numberACTRN12617000079347. NCT03089086; Pre-results.

Infections with Neisseria meningitidis and Neisseria gonorrhoeae have different clinical manifestations, but the bacteria share up to 80–90% genome sequence identity. The recombinant meningococcal serogroup B (MenB) vaccine 4CMenB consists of four antigenic components that can be present in non-B meningococcal and gonococcal strains. This comprehensive review summarizes scientific evidence on the genotypic and phenotypic similarities between vaccine antigens and their homologs expressed by non-B meningococcal and gonococcal strains. It also includes immune responses of 4CMenB-vaccinated individuals and effectiveness and impact of 4CMenB against these strains. Varying degrees of strain coverage were estimated depending on the non-B meningococcal serogroup and antigenic repertoire. 4CMenB elicits immune responses against non-B meningococcal serogroups and N. gonorrhoeae. Real-world evidence showed risk reductions of 69% for meningococcal serogroup W clonal complex 11 disease and 40% for gonorrhea after 4CMenB immunization. In conclusion, functional antibody activity and real-world evidence indicate that 4CMenB has the potential to provide some protection beyond MenB disease.

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