BACKGROUND: One schedule for the capsular group B meningococcal vaccine 4CMenB is 2 doses that are administered 2 months apart for children aged 12-23 months, with a booster dose 12-24 months later. Our objective was to provide data on persistence of human serum bactericidal antibody (hSBA) titres in children up to 4 years of age after initial doses at 12-24 months, and immunogenicity of a booster dose at 48 months of age compared with vaccine-naive children. METHODS: Children previously immunized, as part of a randomized controlled trial, with 2 doses of 4CMenB vaccine at 12-24 months of age received a booster at 4 years of age. Vaccine-naive age-matched toddlers received 2 doses of 4CMenB. Human serum bactericidal antibody titres against reference strains H44/76, 5/99, NZ98/254 and M10713 were evaluated before and after innoculation with 4CMenB vaccine in 4-year-old children. RESULTS: Of 332 children in the study, 123 had previously received 4CMenB and 209 were vaccine-naive controls. Before the booster, the proportions of participants (previously vaccinated groups compared with controls) with hSBA titres of 1:5 or more were as follows: 9%-11% v. 1% (H44/76), 84%-100% v. 4% (5/99), 0%-18% v. 0% (NZ98/254) and 59%-60% v. 60% (M10713). After 1 dose of 4CMenB in previously immunized children, the proportions of participants achieving hSBA titres of 1:5 or more were 100% (H44/76 and 5/99), 70%-100% (NZ98/254) and 90%-100% (M10713). INTERPRETATION: We found that waning of hSBA titres by 4 years of age occurred after 2 doses of 4CMenB vaccine administered at 12-24 months, and doses at 12-24 months have a priming effect on the immune system. A booster may be necessary to maintain hSBA titres of 1:5 or more among those children with increased disease risk. Trial registration: ClinicalTrials.gov, no. NCT01717638.

Oxford Vaccine Group Department of Paediatrics Siena Italy

Zobrazit více v PubMed

Cartwright KA, Stuart JM, Jones DM, et al. The Stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica. Epidemiol Infect 1987;99:591–601. PubMed PMC

Brandtzaeg P, van Deuren M. Classification and pathogenesis of meningococcal infections. Methods Mol Biol 2012;799:21–35. PubMed

Ovstebo R, Hellerud BC, Coureuil M, et al. Pathogenesis of invasive disease. In: Feavers I, Pollard AJ, Sadarangani M, editors. Handbook of meningococcal disease management. Switzerland: Springer; 2016:25–43.

Pace D, Pollard AJ. Meningococcal disease: clinical presentation and sequelae. Vaccine 2012;30(Suppl 2):B3–9. PubMed

Buysse CM, Oranje AP, Zuidema E, et al. Long-term skin scarring and orthopaedic sequelae in survivors of meningococcal septic shock. Arch Dis Child 2009; 94:381–6. PubMed

Buysse CM, Raat H, Hazelzet JA, et al. Surviving meningococcal septic shock: health consequences and quality of life in children and their parents up to 2 years after pediatric intensive care unit discharge. Crit Care Med 2008;36: 596–602. PubMed

Buysse CM, Vermunt LC, Raat H, et al. Surviving meningococcal septic shock in childhood: long-term overall outcome and the effect on health-related quality of life. Crit Care 2010;14:R124. PubMed PMC

Stein-Zamir C, Shoob H, Sokolov I, et al. The clinical features and long-term sequelae of invasive meningococcal disease in children. Pediatr Infect Dis J 2014; 33: 777–9. PubMed

Borg J, Christie D, Coen PG, et al. Outcomes of meningococcal disease in adolescence: prospective, matched-cohort study. Pediatrics 2009;123:e502–9. PubMed

Judge D, Nadel S, Vergnaud S, et al. Psychiatric adjustment following meningococcal disease treated on a PICU. Intensive Care Med 2002;28:648–50. PubMed

Sander J, Bay D, Gedde-Dahl TW, et al. Late sequelae after meningococcal disease. A controlled study in young men. NIPH Ann 1984;7:3–11. PubMed

Borrow R, Abad R, Trotter C, et al. Effectiveness of meningococcal serogroup C vaccine programmes. Vaccine 2013;31:4477–86. PubMed

MenAfriCar consortium. The diversity of meningococcal carriage across the African meningitis belt and the impact of vaccination with a group A meningococcal conjugate vaccine. J Infect Dis 2015;212:1298–307. PubMed PMC

Halperin SA, Bettinger JA, Greenwood B, et al. The changing and dynamic epidemiology of meningococcal disease. Vaccine 2012;30(Suppl 2):B26–36. PubMed

Bettinger JA, Scheifele DW, Le Saux N, et al. The disease burden of invasive meningococcal serogroup B disease in Canada. Pediatr Infect Dis J 2013;32:e20–5. PubMed

Drysdale SB, Pollard AJ. Group B meningococcal vaccine science and policy. J Infect 2015;71(Suppl 1):S15–20. PubMed

Watson PS, Turner DP. Clinical experience with the meningococcal B vaccine, Bexsero(®): prospects for reducing the burden of meningococcal serogroup B disease. Vaccine 2016;34:875–80. PubMed

Bexsero. Summary of product characteristics. London (UK): European Medicines Agency; 2012. Available: www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002333/WC500137881.pdf (accessed 2016 Feb. 14).

Basta NE, Mahmoud AA, Wolfson J, et al. Immunogenicity of a meningococcal B vaccine during a university outbreak. N Engl J Med 2016;375:220–8. PubMed PMC

Iro MA, Snape MD, Voysey M, et al. Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24 months and immunogenicity of a fifth dose administered at 4 years of age - a phase 3 extension to a randomised controlled trial. Vaccine 2017;35:395–402. PubMed

Snape MD, Voysey M, Biostat M, et al. Persistence of bactericidal antibodies following infant serogroup B meningococcal immunization and booster dose response at 12, 18 or 24 months of age. Pediatr Infect Dis J 2016;35:e113–23. PubMed

Snape MD, Dawson T, Oster P, et al. Immunogenicity of two investigational serogroup B meningococcal vaccines in the first year of life: a randomized comparative trial. Pediatr Infect Dis J 2010;29:e71–9. PubMed

Frasch CE, Borrow R, Donnelly J. Bactericidal antibody is the immunologic surrogate of protection against meningococcal disease. Vaccine 2009;27(Suppl 2):B112–6. PubMed

Parikh SR, Andrews NJ, Beebeejaun K, et al. Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study. Lancet 2016; 388: 2775–82. PubMed

Vesikari T, Prymula R, Merrall E, et al. Meningococcal serogroup B vaccine (4CMenB): Booster dose in previously vaccinated infants and primary vaccination in toddlers and two-year-old children. Vaccine 2015;33:3850–8. PubMed

Snape MD, Saroey P, John TM, et al. Persistence of bactericidal antibodies following early infant vaccination with a serogroup B meningococcal vaccine and immunogenicity of a preschool booster dose. CMAJ 2013;185:E715–24. PubMed PMC

McQuaid F, Snape MD, John TM, et al. Persistence of bactericidal antibodies to 5 years of age after immunization with serogroup B meningococcal vaccines at 6, 8, 12 and 40 months of age. Pediatr Infect Dis J 2014;33:760–6. PubMed

McQuaid F, Snape MD, John TM, et al. Persistence of specific bactericidal antibodies at 5 years of age after vaccination against serogroup B meningococcus in infancy and at 40 months. CMAJ 2015;187:E215–23. PubMed PMC

Vogel U, Taha MK, Vazquez JA, et al. Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Europe: a qualitative and quantitative assessment. Lancet Infect Dis 2013;13:416–25. PubMed

Ciaravino G, Högberg LD, Ködmön C, et al. EDCD Surveillance report: surveillance of invasive bacterial diseases in Europe, 2012. Invasive pneumococcal disease, invasive Haemophilus influenzae disease and invasive meningococcal disease. Stockholm: European Centre for Disease Prevention and Control; 2015. Available: http://ecdc.europa.eu/en/publications/Publications/Surveillance%20of%20IBD%20in%20Europe%202012.pdf (accessed 2016 Oct. 8).

Santolaya ME, O’Ryan M, Valenzuela MT, et al. Persistence of antibodies in adolescents 18–24 months after immunization with one, two, or three doses of 4CMenB meningococcal serogroup B vaccine. Hum Vaccin Immunother 2013;9:2304–10. PubMed PMC

Marshall HS, Richmond PC, Beeslaar J, et al. Meningococcal serogroup B–specific responses after vaccination with bivalent rLP2086: 4 year follow-up of a randomised, single-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis 2017;17:58–67. PubMed

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01717638