First immunogenicity data for the UK serogroup B meningococcal vaccination schedule in infants

In North America and Europe, serogroup B causes most cases of meningococcal disease in infants.1US CDCEnhanced meningococcal disease surveillance report. US Centers for Disease Control and Prevention, 2018https://www.cdc.gov/meningococcal/downloads/NCIRD-EMS-Report-2018.pdfDate accessed: November 20, 2020Google Scholar, 2PHEInvasive meningococcal disease in England: annual laboratory confirmed reports for the epidemiological year 2018 to 2019. Public Health England, London2019https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/842368/hpr3819_IMD-ann.pdfDate accessed: November 20, 2020Google Scholar, 3ECDCSurveillance atlas of infectious diseases. European Centre for Disease Prevention and Control, 2020https://www.ecdc.europa.eu/en/meningococcal-disease/surveillance-and-disease-data/atlasDate accessed: November 20, 2020Google Scholar The first serogroup B meningococcal vaccine, 4CMenB (Bexsero; GlaxoSmithKline, Rixensart, Belgium), was authorised in the EU in 2013 as a 3 + 1 schedule for infants, with three doses administered during the first year of life and a booster dose at 12 months.4Ladhani SN Andrews N Parikh SR et al.Vaccination of infants with meningococcal group B vaccine (4CMenB) in England.N Engl J Med. 2020; 382: 309-317Crossref PubMed Scopus (95) Google Scholar In 2015, the UK was the first country to implement a routine infant 4CMenB immunisation programme. However, cost-effectiveness and epidemiological considerations led the UK to choose a novel 2 + 1 schedule with doses at 2, 4, and 12 months of age, despite an absence of corresponding immunogenicity data.5DoH–PHEJCVI position statement on use of Bexsero® meningococcal B vaccine in the UK. Department of Health and Public Health England, 2014https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/294245/JCVI_Statement_on_MenB.pdfDate accessed: November 20, 2020Google Scholar 5 years later, the study by Kimberly Davis and colleagues in The Lancet Infectious Diseases provides immunogenicity data for the UK 4CMenB vaccination schedule.6Davis K Valente Pinto M Andrews NJ et al.Immunogenicity of the UK group B meningococcal vaccine (4CMenB) schedule against groups B and C meningococcal strains (Sched3): outcomes of a multicentre, open-label, randomised controlled trial.Lancet Infect Dis. 2021; (published online Jan 8.)https://doi.org/10.1016/S1473-3099(20)30600-9Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar Following the two-dose primary series, 95·3–97·9% of participants had human complement serum bactericidal antibody (hSBA) titres of at least 4 for factor H binding protein (fHbp), 86·5–88·5% for porin A (PorA), and 100% for Neisserial adhesin A (NadA). No test strain was included for the fourth vaccine antigen, neisserial heparin-binding antigen (NHBA). Geometric mean titres against strains containing NadA or PorA, but not fHbp, increased after the 12-month booster dose. These findings show that the UK 4CMenB vaccination schedule is immunogenic in most infants. Although these data are the first on the UK 2 + 1 immunisation schedule, a previous study has evaluated an alternative 2 + 1 schedule with doses administered at 3·5, 5, and 11 months of age.7Martinón-Torres F Safadi MAP Martinez AC et al.Reduced schedules of 4CMenB vaccine in infants and catch-up series in children: immunogenicity and safety results from a randomised open-label phase 3b trial.Vaccine. 2017; 35: 3548-3557Crossref PubMed Scopus (38) Google Scholar, 8Biolchi A Tomei S Santini L et al.Evaluation of strain coverage of the multicomponent meningococcal serogroup B vaccine (4CMenB) administered in infants according to different immunisation schedules.Hum Vaccin Immunother. 2019; 15: 725-731Crossref PubMed Scopus (12) Google Scholar Davis and colleagues report lower proportions of vaccine recipients with hSBA titres of at least 4 for fHbp-containing and PorA-containing strains compared with previous data on the 3·5–5–11 month schedule, suggesting that beginning the primary series 6 weeks earlier might be less immunogenic.7Martinón-Torres F Safadi MAP Martinez AC et al.Reduced schedules of 4CMenB vaccine in infants and catch-up series in children: immunogenicity and safety results from a randomised open-label phase 3b trial.Vaccine. 2017; 35: 3548-3557Crossref PubMed Scopus (38) Google Scholar However, as the prevaccine peak of serogroup B disease in UK infants occurred at 5 months of age, earlier vaccine administration has the potential to prevent more cases, even if immunogenicity is somewhat reduced.5DoH–PHEJCVI position statement on use of Bexsero® meningococcal B vaccine in the UK. Department of Health and Public Health England, 2014https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/294245/JCVI_Statement_on_MenB.pdfDate accessed: November 20, 2020Google Scholar The absence of an NHBA test strain in this study is an important caveat. In the 3·5–5–11 month schedule, most individuals had a poor immune response against the NHBA-containing strain after the primary series.7Martinón-Torres F Safadi MAP Martinez AC et al.Reduced schedules of 4CMenB vaccine in infants and catch-up series in children: immunogenicity and safety results from a randomised open-label phase 3b trial.Vaccine. 2017; 35: 3548-3557Crossref PubMed Scopus (38) Google Scholar Assuming that immunogenicity with the UK schedule would be similar or lower as for the other 4CMenB antigens, many infants receiving the UK infant schedule might mount an insufficient immune response to NHBA. If correct, this assumption is concerning, since NHBA contributes to predicted coverage for half of the 66% of UK serogroup B meningococcal strains that are expected to be covered by 4CMenB.9Parikh SR Newbold L Slater S et al.Meningococcal serogroup B strain coverage of the multicomponent 4CMenB vaccine with corresponding regional distribution and clinical characteristics in England, Wales, and Northern Ireland, 2007–08 and 2014–15: a qualitative and quantitative assessment.Lancet Infect Dis. 2017; 17: 754-762Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar In an initial report of two breakthrough disease cases among 4CMenB-vaccinated UK infants, one of the infecting meningococcal strains was predicted to be covered by 4CMenB on the basis of NHBA alone and one on the basis of NHBA and fHbp.10Bai X Lucidarme J Patel S et al.Enhanced surveillance of 4CMenB by the meningococcal antigen typing system in England, the first 29 months. EMGM, Lisbon, PortugalMay 27–30, 2019Google Scholar Vaccine effectiveness for the UK serogroup B vaccination programme was reported in 2020: 52·7% effectiveness was observed after the primary series and 59·1% after the booster dose, with a 75% reduction in incidence among vaccine-eligible children.4Ladhani SN Andrews N Parikh SR et al.Vaccination of infants with meningococcal group B vaccine (4CMenB) in England.N Engl J Med. 2020; 382: 309-317Crossref PubMed Scopus (95) Google Scholar However, there are wide CIs around these point estimates; even 0% vaccine effectiveness was not ruled out.4Ladhani SN Andrews N Parikh SR et al.Vaccination of infants with meningococcal group B vaccine (4CMenB) in England.N Engl J Med. 2020; 382: 309-317Crossref PubMed Scopus (95) Google Scholar Given the challenges in establishing effectiveness, immunogenicity data provide reassurance that the UK vaccination programme can reduce meningococcal disease in infants. Limited data are available to assess whether effectiveness is higher with other 4CMenB schedules. In response to a prolonged outbreak in Quebec, Canada, people aged 2 months–20 years were vaccinated using a 3 + 1 schedule for infants aged 2–5 months and fewer doses in older age groups.11De Wals P Deceuninck G Lefebvre B et al.Impact of an immunization campaign to control an increased incidence of serogroup B meningococcal disease in one region of Quebec, Canada.Clin Infect Dis. 2017; 64: 1263-1267Crossref PubMed Scopus (49) Google Scholar The vaccination campaign was estimated to be 79% effective (with a wide CI of −236% to 99%) in the 4 years following the campaign.12Deceuninck G Lefebvre B Tsang R Betala-Belinga JF De Serres G De Wals P Impact of a mass vaccination campaign against serogroup B meningococcal disease in the Saguenay-Lac-Saint-Jean region of Quebec four years after its launch.Vaccine. 2019; 37: 4243-4245Crossref PubMed Scopus (31) Google Scholar However, the results cannot be directly compared to UK effectiveness estimates given the different target ages; in addition, the cases in Quebec were predominantly caused by a single serogroup B clone. With countries in Europe introducing a mix of 3 + 1 and 2 + 1 infant schedules,13Isitt C Cosgrove CA Ramsay ME Ladhani SN Success of 4CMenB in preventing meningococcal disease: evidence from real-world experience.Arch Dis Childhood. 2020; 105: 784-790Crossref PubMed Scopus (14) Google Scholar comparing meningococcal disease epidemiology and vaccine effectiveness in a variety of settings will be of interest to understand whether immunological differences between schedules translate into differences in vaccine effect. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. We declare no competing interests. Immunogenicity of the UK group B meningococcal vaccine (4CMenB) schedule against groups B and C meningococcal strains (Sched3): outcomes of a multicentre, open-label, randomised controlled trialThese data support the recent change to the licensed European schedule for 4CMenB to add an infant 2 + 1 schedule, as used in the routine UK vaccine programme with an effectiveness of 59·1%. When compared with historical data, our data do not suggest that effectiveness would be higher with a 3 + 1 schedule, however a suboptimal boost response for bactericidal antibodies against vaccine antigen fHbp suggests a need for ongoing surveillance for vaccine breakthroughs due to fHbp-matched strains. Changing from a 2 + 1 to a 1 + 1 schedule for PCV13 for the UK is unlikely to affect protection against diphtheria, tetanus, and Hib, however an unexpected reduction in bactericidal antibodies against MenC seen with the new schedule suggests that ongoing surveillance for re-emergent MenC disease is important. Full-Text PDF Open Access

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