Immunogenicity and reactogenicity of a reduced schedule of a 4-component capsular group b meningococcal vaccine: A randomized controlled trial in infants

Marta Valente Pinto; Daniel O'Connor; Ushma Galal; Elizabeth A. Clutterbuck; Hannah Robinson; Emma Plested; Sagida Bibi; Susana Camara Pellisso; Harri Hughes; Simon Kerridge; Yama F. Mujadidi; Helen Findlow; Raymond Borrow; Matthew D. Snape; Andrew J. Pollard

doi:10.1093/OFID/OFAA143

Immunogenicity and reactogenicity of a reduced schedule of a 4-component capsular group b meningococcal vaccine: A randomized controlled trial in infants

Marta Valente Pinto^*
, Daniel O'Connor
, Ushma Galal
, Elizabeth A. Clutterbuck
, Hannah Robinson
, Emma Plested
, Sagida Bibi
, Susana Camara Pellisso
, Harri Hughes
, Simon Kerridge
, Yama F. Mujadidi
, Helen Findlow
, Raymond Borrow
, Matthew D. Snape
, Andrew J. Pollard

^*Corresponding author for this work

Manchester Meningococcal Reference Unit General

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Background. The 4-component capsular group B meningococcal vaccine (4CMenB) was licensed as a 4-dose infant schedule but introduced into the United Kingdom as 3 doses at 2, 4, and 12 months of age. We describe the immunogenicity and reactogenicity of the 2 + 1 schedule in infants.

Methods. Infants were randomized to receive 4CMenB with routine immunizations (test group) at 2, 4, and 12 months or 4CMenB alone at 6, 8, and 13 months of age (control group). Serum bactericidal antibody (SBA) assay against a serogroup B meningococcal reference strain (44/76-SL), memory B-cell responses to factor H binding protein, Neisseria adhesion protein A, Neisseria heparin binding antigen, Porin A (PorA), and reactogenicity was measured.

Results. One hundred eighty-seven infants were randomized (test group: 94; control group: 93). In the test group, 4CMenB induced SBA titers above the putative protective threshold (1:4) after primary and booster doses in 97% of participants. Postbooster, the SBA GMT (72.1; 95% confidence interval [CI], 51.7-100.4) was numerically higher than the serum bactericidal antibody geometric mean titre (SBA GMT) determined post-primary vaccination (48.6; 95% CI, 37.2-63.4). After primary immunizations, memory B-cell responses did not change when compared with baseline controls, but frequencies significantly increased after booster. Higher frequency of local and systemic adverse reactions was associated with 4CMenB.

Conclusions. A reduced schedule of 4CMenB was immunogenic and established immunological memory after booster.

Original language	English
Article number	143
Journal	Open Forum Infectious Diseases
Volume	7
Issue number	5
Early online date	29 Apr 2020
DOIs	https://doi.org/10.1093/OFID/OFAA143
Publication status	Published - 27 May 2020

Bibliographical note

Funding Information:
We thank the participants and their parents, the Central Midlands South Child Health Information Services, the NHS South, Central and West Commissioning Support Unit formerly known as Berkshire Healthcare NHS Foundation Trust, the Milton Keynes Primary Care Trust, the Buckinghamshire Primary Care Trust, and Oxfordshire Primary Care Trust Child Health Department for their assistance. We thank the Oxford Vaccine Group clinical staff for their help in recruitment, vaccination, and follow-up of participants. We thank the laboratory staff at OVG for sample processing and assay development during the study. Financial support. The study was funded by European Union’s seventh Framework program under EC-GA no. 279185 (EUCLIDS) and supported by National Institute of Health Research (NIHR) Oxford Biomedical Research Centre (BRC). A.J.P. is supported by the NIHR Oxford Biomedical Research Centre and is an NIHR Senior Investigator.

Publisher Copyright:
© 2020 Oxford University Press. All rights reserved.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

4-Component Capsular Group B Meningococcal Vaccine
4cmenb
Immunogenicity
Memory B Cells
Meningococcal Disease
Reactogenicity.
Reduced Schedule

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10.1093/OFID/OFAA143

Cite this

Pinto, M. V., O'Connor, D., Galal, U., Clutterbuck, E. A., Robinson, H., Plested, E., Bibi, S., Pellisso, S. C., Hughes, H., Kerridge, S., Mujadidi, Y. F., Findlow, H., Borrow, R., Snape, M. D., & Pollard, A. J. (2020). Immunogenicity and reactogenicity of a reduced schedule of a 4-component capsular group b meningococcal vaccine: A randomized controlled trial in infants. Open Forum Infectious Diseases, 7(5), Article 143. https://doi.org/10.1093/OFID/OFAA143

@article{1fe8fab4a04b4a1a9809030bcb20aac2,

title = "Immunogenicity and reactogenicity of a reduced schedule of a 4-component capsular group b meningococcal vaccine: A randomized controlled trial in infants",

abstract = "Background. The 4-component capsular group B meningococcal vaccine (4CMenB) was licensed as a 4-dose infant schedule but introduced into the United Kingdom as 3 doses at 2, 4, and 12 months of age. We describe the immunogenicity and reactogenicity of the 2 + 1 schedule in infants. Methods. Infants were randomized to receive 4CMenB with routine immunizations (test group) at 2, 4, and 12 months or 4CMenB alone at 6, 8, and 13 months of age (control group). Serum bactericidal antibody (SBA) assay against a serogroup B meningococcal reference strain (44/76-SL), memory B-cell responses to factor H binding protein, Neisseria adhesion protein A, Neisseria heparin binding antigen, Porin A (PorA), and reactogenicity was measured. Results. One hundred eighty-seven infants were randomized (test group: 94; control group: 93). In the test group, 4CMenB induced SBA titers above the putative protective threshold (1:4) after primary and booster doses in 97\% of participants. Postbooster, the SBA GMT (72.1; 95\% confidence interval [CI], 51.7-100.4) was numerically higher than the serum bactericidal antibody geometric mean titre (SBA GMT) determined post-primary vaccination (48.6; 95\% CI, 37.2-63.4). After primary immunizations, memory B-cell responses did not change when compared with baseline controls, but frequencies significantly increased after booster. Higher frequency of local and systemic adverse reactions was associated with 4CMenB. Conclusions. A reduced schedule of 4CMenB was immunogenic and established immunological memory after booster.",

keywords = "4-Component Capsular Group B Meningococcal Vaccine, 4cmenb, Immunogenicity, Memory B Cells, Meningococcal Disease, Reactogenicity., Reduced Schedule",

author = "Pinto, \{Marta Valente\} and Daniel O'Connor and Ushma Galal and Clutterbuck, \{Elizabeth A.\} and Hannah Robinson and Emma Plested and Sagida Bibi and Pellisso, \{Susana Camara\} and Harri Hughes and Simon Kerridge and Mujadidi, \{Yama F.\} and Helen Findlow and Raymond Borrow and Snape, \{Matthew D.\} and Pollard, \{Andrew J.\}",

note = "Funding Information: We thank the participants and their parents, the Central Midlands South Child Health Information Services, the NHS South, Central and West Commissioning Support Unit formerly known as Berkshire Healthcare NHS Foundation Trust, the Milton Keynes Primary Care Trust, the Buckinghamshire Primary Care Trust, and Oxfordshire Primary Care Trust Child Health Department for their assistance. We thank the Oxford Vaccine Group clinical staff for their help in recruitment, vaccination, and follow-up of participants. We thank the laboratory staff at OVG for sample processing and assay development during the study. Financial support. The study was funded by European Union{\textquoteright}s seventh Framework program under EC-GA no. 279185 (EUCLIDS) and supported by National Institute of Health Research (NIHR) Oxford Biomedical Research Centre (BRC). A.J.P. is supported by the NIHR Oxford Biomedical Research Centre and is an NIHR Senior Investigator. Publisher Copyright: {\textcopyright} 2020 Oxford University Press. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2020",

month = may,

day = "27",

doi = "10.1093/OFID/OFAA143",

language = "English",

volume = "7",

journal = "Open Forum Infectious Diseases",

issn = "2328-8957",

publisher = "Oxford University Press",

number = "5",

}

Pinto, MV, O'Connor, D, Galal, U, Clutterbuck, EA, Robinson, H, Plested, E, Bibi, S, Pellisso, SC, Hughes, H, Kerridge, S, Mujadidi, YF, Findlow, H, Borrow, R, Snape, MD & Pollard, AJ 2020, 'Immunogenicity and reactogenicity of a reduced schedule of a 4-component capsular group b meningococcal vaccine: A randomized controlled trial in infants', Open Forum Infectious Diseases, vol. 7, no. 5, 143. https://doi.org/10.1093/OFID/OFAA143

TY - JOUR

T1 - Immunogenicity and reactogenicity of a reduced schedule of a 4-component capsular group b meningococcal vaccine

T2 - A randomized controlled trial in infants

AU - Pinto, Marta Valente

AU - O'Connor, Daniel

AU - Galal, Ushma

AU - Clutterbuck, Elizabeth A.

AU - Robinson, Hannah

AU - Plested, Emma

AU - Bibi, Sagida

AU - Pellisso, Susana Camara

AU - Hughes, Harri

AU - Kerridge, Simon

AU - Mujadidi, Yama F.

AU - Findlow, Helen

AU - Borrow, Raymond

AU - Snape, Matthew D.

AU - Pollard, Andrew J.

N1 - Funding Information: We thank the participants and their parents, the Central Midlands South Child Health Information Services, the NHS South, Central and West Commissioning Support Unit formerly known as Berkshire Healthcare NHS Foundation Trust, the Milton Keynes Primary Care Trust, the Buckinghamshire Primary Care Trust, and Oxfordshire Primary Care Trust Child Health Department for their assistance. We thank the Oxford Vaccine Group clinical staff for their help in recruitment, vaccination, and follow-up of participants. We thank the laboratory staff at OVG for sample processing and assay development during the study. Financial support. The study was funded by European Union’s seventh Framework program under EC-GA no. 279185 (EUCLIDS) and supported by National Institute of Health Research (NIHR) Oxford Biomedical Research Centre (BRC). A.J.P. is supported by the NIHR Oxford Biomedical Research Centre and is an NIHR Senior Investigator. Publisher Copyright: © 2020 Oxford University Press. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2020/5/27

Y1 - 2020/5/27

N2 - Background. The 4-component capsular group B meningococcal vaccine (4CMenB) was licensed as a 4-dose infant schedule but introduced into the United Kingdom as 3 doses at 2, 4, and 12 months of age. We describe the immunogenicity and reactogenicity of the 2 + 1 schedule in infants. Methods. Infants were randomized to receive 4CMenB with routine immunizations (test group) at 2, 4, and 12 months or 4CMenB alone at 6, 8, and 13 months of age (control group). Serum bactericidal antibody (SBA) assay against a serogroup B meningococcal reference strain (44/76-SL), memory B-cell responses to factor H binding protein, Neisseria adhesion protein A, Neisseria heparin binding antigen, Porin A (PorA), and reactogenicity was measured. Results. One hundred eighty-seven infants were randomized (test group: 94; control group: 93). In the test group, 4CMenB induced SBA titers above the putative protective threshold (1:4) after primary and booster doses in 97% of participants. Postbooster, the SBA GMT (72.1; 95% confidence interval [CI], 51.7-100.4) was numerically higher than the serum bactericidal antibody geometric mean titre (SBA GMT) determined post-primary vaccination (48.6; 95% CI, 37.2-63.4). After primary immunizations, memory B-cell responses did not change when compared with baseline controls, but frequencies significantly increased after booster. Higher frequency of local and systemic adverse reactions was associated with 4CMenB. Conclusions. A reduced schedule of 4CMenB was immunogenic and established immunological memory after booster.

AB - Background. The 4-component capsular group B meningococcal vaccine (4CMenB) was licensed as a 4-dose infant schedule but introduced into the United Kingdom as 3 doses at 2, 4, and 12 months of age. We describe the immunogenicity and reactogenicity of the 2 + 1 schedule in infants. Methods. Infants were randomized to receive 4CMenB with routine immunizations (test group) at 2, 4, and 12 months or 4CMenB alone at 6, 8, and 13 months of age (control group). Serum bactericidal antibody (SBA) assay against a serogroup B meningococcal reference strain (44/76-SL), memory B-cell responses to factor H binding protein, Neisseria adhesion protein A, Neisseria heparin binding antigen, Porin A (PorA), and reactogenicity was measured. Results. One hundred eighty-seven infants were randomized (test group: 94; control group: 93). In the test group, 4CMenB induced SBA titers above the putative protective threshold (1:4) after primary and booster doses in 97% of participants. Postbooster, the SBA GMT (72.1; 95% confidence interval [CI], 51.7-100.4) was numerically higher than the serum bactericidal antibody geometric mean titre (SBA GMT) determined post-primary vaccination (48.6; 95% CI, 37.2-63.4). After primary immunizations, memory B-cell responses did not change when compared with baseline controls, but frequencies significantly increased after booster. Higher frequency of local and systemic adverse reactions was associated with 4CMenB. Conclusions. A reduced schedule of 4CMenB was immunogenic and established immunological memory after booster.

KW - 4-Component Capsular Group B Meningococcal Vaccine

KW - 4cmenb

KW - Immunogenicity

KW - Memory B Cells

KW - Meningococcal Disease

KW - Reactogenicity.

KW - Reduced Schedule

UR - https://www.scopus.com/pages/publications/85101316973

U2 - 10.1093/OFID/OFAA143

DO - 10.1093/OFID/OFAA143

M3 - Article

AN - SCOPUS:85101316973

SN - 2328-8957

VL - 7

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

IS - 5

M1 - 143

ER -

Immunogenicity and reactogenicity of a reduced schedule of a 4-component capsular group b meningococcal vaccine: A randomized controlled trial in infants

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

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