Persistence of immunity after vaccination with a capsular group B meningococcal vaccine in 3 different toddler schedules

Abstract

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.

Conflict of interest statement

Competing interests: Manish Sadarangani has received a grant from Novartis during the conduct of this study (Novartis Vaccines Division was subsequently acquired by the GSK group of companies) and a grant for investigator-initiated research studies outside the submitted work from Pfizer. Manish Sadarangani has also received payment as site investigator/co-investigator for multicentre trials from Variation Biotechnologies and Merck. Matthew Snape has received a grant from Novartis during the conduct of this study (Novartis Vaccines Division was subsequently acquired by GSK group of companies) and grants paid to his institution for work as an investigator on clinical trials from Novartis Vaccines and Diagnostics (subsequently acquired by GSK group of companies), GSK group of companies, Pfizer, Janssen, MedImmune, Alios BioPharma and Ablynx. He has also received support for travel and accommodation to attend international conferences from GSK group of companies, and he has received support paid to his institution as a member of the advisory board for Sanofi-Pasteur MSD and as a consultant for MedImmune. Matthew Snape receives salary support from the National Institute for Health Research Oxford Biomedical Research Centre and is a Jenner Investigator. Adam Finn has received grants paid to his institution from Novartis, GSK group of companies, Pfizer and Sanofi-Pasteur MSD for studies outside the submitted work, and a grant from Novartis (Novartis Vaccines Division was subsequently acquired by the GSK group of companies) for the submitted work. Owing to his membership on the Joint Committee on Vaccination and Immunisation for the United Kingdom Department of Health, Adam Finn no longer gives lectures or undertakes advisory work for industry, either paid or unpaid. Paul Heath has received grants paid to his institution from GSK group of companies, Sanofi-Pasteur MSD and Novartis for studies outside the submitted work, and a grant from Novartis for the submitted work. Gianni Bona has received lecture fees and nonfinancial support for clinical trials during the conduct of this study from Novartis Vaccines and Diagnostics, and support from Novartis Vaccines and Diagnostics, GSK group of companies, Sanofi-Pasteur and Pfizer as an investigator for clinical trials outside the submitted work. Susanna Esposito has received a grant paid to her institution from Novartis Vaccines and Diagnostics; grants from Novartis Vaccines and Diagnostics, GSK group of companies, Pfizer, Sanofi-Aventis and Sanofi-Pasteur MSD; and personal fees (in the form of consultant and speaker fees, and reimbursements for travel and accommodation) from Novartis Vaccines and Diagnostics, GSK group of companies, Pfizer and MedImmune. Javier Diez-Domingo has received reimbursement for being a member of the advisory committees for GSK group of companies and Pfizer, as well as travel support from Pfizer. Roman Prymula received a grant for the submitted work from Novartis, and has received grants from Novartis, Sanofi-Pasteur MSD and GSK group of companies outside the submitted work. Mildred Iro has received nonfinancial support for travel to conferences from GSK group of companies. Andrew Pollard has received a grant from Novartis during the conduct of this study, and grants from Pfizer and Okairos in the past 36 months. His department received unrestricted educational grants from Pfizer, GSK group of companies and AstraZeneca in July 2016, and Gilead, MSD, GSK group of companies and AstraZeneca in June 2017 for a course on Infection and immunity in children. Andrew Pollard is the chair of UK Department of Health’s Joint Committee on Vaccination and Immunisation, and the Vaccines Scientific Advisory group of the European Medicines Agency, and is a member of the World Health Organization’s Strategic Advisory Group of Experts (SAGE). Adefowope Odueyungbo was a GSK employee at the time the study was conducted (formerly Novartis Vaccines and Diagnostics). Daniela Toneatto declares that she is employed by and holds shares in the GSK group of companies. Andrew Pollard, Paul Heath, Matthew Snape, Manish Sadarangani and Adam Finn do not receive any personal remuneration from vaccine manufacturers.

© 2017 Canadian Medical Association or its licensors.

Figures

Figure 1:

Flow diagram for selection of participants. All participants in the follow-up cohort received 2 previous doses of 4CMenB vaccine at 12 and 14 mo (Group 1), 18 and 20 mo (Group 2) or 24 and 26 mo (Group 3) in a previous study. The vaccine-naive cohort had not received any 4CMenB doses previously. All children received 1 dose at 4 yr of age; the vaccine-naive cohort were given an additional dose 2 mo later. Blood samples for persistence analysis were taken before any doses were given at 4 yr of age (prevaccine time point) and for booster analysis 30 d after each dose. Safety data were collected after each dose. Time points where blood samples were taken for measurement of hSBA are shown slightly offset from the pain participant flow because inability to measure SBA did not preclude ongoing involvement of the participant in the study (i.e., this did not result in withdrawal or loss to follow-up). hSBA = human serum bactericidal antibody, 4CMenB = multicomponent meningococcal serogroup B vaccine.

Figure 2:

Proportion of participants with hSBA titres ≥ 1:5 at each time point against each strain. Proportion of participants with hSBA titres ≥ 1:5 at 1 mo after the previous dose (Groups 1, 2 and 3 only) is based on data from Snape and colleagues. Time points from this study include prevaccine (before first dose, all groups), 1 mo postdose 1 (all groups) and 1 mo postdose 2 (Group 4 only). The prevaccine category for Groups 1, 2 and 3 represents persistence of hSBA following the vaccine doses at 12, 18 or 24 mo. Participants in Group 1 were not tested for M10713 strains at 1 mo following the previous dose in the prior study because the strain was not available. Bars represent overall percentage of participants achieving an hSBA titre ≥ 1:5, with error bars representing 95% confidence intervals. Data are shown separately for the 4 indicator strains: (A) H44/76 (fHbp response), (B) 5/99 (NadA response), (C) NZ98/254 (PorA response) and (D) M10713 (NHBA response). All participants in the follow-up cohort received 2 previous doses of 4CMenB vaccine at 12 and 14 mo (Group 1), 18 and 20 mo (Group 2) or 24 and 26 mo (Group 3) in a previous study. Group 4 included participants with no previous 4CMenB vaccination. fHbp = factor H–binding protein, hSBA = human serum bactericidal antibody, NadA = Neisserial adhesin A, NHBA = Neisseria heparin binding antigen, PorA = porin A.

Figure 3:

Geometric mean titres for hSBA at each time point against each strain. Values of geometric mean titres at 1 mo after the previous dose (Groups 1, 2 and 3 only) are based on data from Snape and colleagues. Time points from this study include prevaccine (before first dose, all groups), 1 mo postdose 1 (all groups) and 1 mo postdose 2 (Group 4 only). Participants in Group 1 were not tested for M10713 strains at 1 mo after the previous dose in the prior study because the strain was not available. Points represent overall GMT, with error bars representing 95% confidence intervals. Data are shown separately for the 4 indicator strains: (A) H44/76 (fHbp response), (B) 5/99 (NadA response), (C) NZ98/254 (PorA response) and (D) M10713 (NHBA response). Human serum bactericidal antibody titre of 1:5 shown as horizontal dashed line on each graph to enable comparison as different Y axis scale on each graph. All participants in the follow-up cohort received 2 previous doses of 4CMenB vaccine at 12 and 14 mo (Group 1), 18 and 20 mo (Group 2) or 24 and 26 mo (Group 3) in a previous study. Group 4 included participants with no previous 4CMenB vaccination. fHbp = factor H–binding protein, GMT = geometric mean titre, hSBA = human serum bactericidal antibody, NadA = Neisserial adhesin A, NHBA = Neisseria heparin binding antigen, PorA = porin A.