Immunogenicity of a single 4CMenB vaccine booster in adolescents 11 years after childhood immunisation

Christine S. Rollier; Christina Dold; Luke Blackwell; Aline Linder; Laura Silva-Reyes; Elizabeth Clutterbuck; Kimberly Davis; Karen Ford; Xinxue Liu; Ann Holland; Hannah Chan; Holly Harbinson; Daniel O'Connor; Ray Borrow; Matthew D. Snape; Andrew J. Pollard

doi:10.1016/j.vaccine.2022.04.085

Immunogenicity of a single 4CMenB vaccine booster in adolescents 11 years after childhood immunisation

Christine S. Rollier^*, Christina Dold, Luke Blackwell, Aline Linder, Laura Silva-Reyes, Elizabeth Clutterbuck, Kimberly Davis, Karen Ford, Xinxue Liu, Ann Holland, Hannah Chan, Holly Harbinson, Daniel O'Connor, Ray Borrow, Matthew D. Snape, Andrew J. Pollard

^*Corresponding author for this work

UK Health Security Agency

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

3 Citations (Scopus)

Abstract

The clinical development of the meningococcal vaccine, 4CMenB, included 2 doses in vaccine-naïve adolescents, which was considered unlikely to be cost-effective for implementation. Theoretically, priming with 4CMenB in early childhood might drive strong immune responses after only a single booster dose in adolescents and reduce programmatic costs. To address this question, children over 11 years old who took part in previous trials involving the administration of 3–5 doses of 4CMenB at infant/preschool age from 2006 were recruited into a post licensure single-centre trial, and were divided into two groups: those who received their last dose at 12 months old (infant group) and those who received their last dose at 3 years old (infant + preschool group). Naïve age-matched controls were randomised to receive one (adolescent 1 group) or two doses at days 0 and 28 (adolescent 2 group) of 4CMenB. Serum bactericidal antibody (SBA) assays using human complement were performed against three reference strains prior to vaccination, and at 1, 6 and 12 months. Previous vaccination was associated with a higher response to a single booster dose at 11 years of age, one-month post-vaccination, when compared with a single dose in naïve age-matched controls. At day 180, the highest responses were observed in participants in the infant + preschool group against strain 5/99 (GMT 316.1 [CI 158.4 to 630.8]), as compared with naïve adolescents who received two doses (GMTs 84.5 [CI 57.7 to 123.6]). When the last dose was received at 12-months of age, responses to a single adolescent dose were not as robust (GMT 61.1 [CI 14.8 to 252.4] to strain 5/99). This descriptive study indicates that the highest SBA responses after a single dose in adolescence were observed in participants who received a preschool dose, suggesting that B cell memory responses are not sufficiently primed at less than 12 months of age. Trial registration EudraCT 2017-004732-11, ISRCTN16774163.

Original language	English
Pages (from-to)	4453-4463
Number of pages	11
Journal	Vaccine
Volume	40
Issue number	32
DOIs	https://doi.org/10.1016/j.vaccine.2022.04.085
Publication status	Published - 30 Jul 2022

Bibliographical note

Funding Information:
the authors thank Emma Plested, David Smith and Rachel Craik for project management, the nurses, clinical trials, IT and lab teams at the Oxford Vaccine Group for excellent work, and the participants. The authors thank the protein production facility and Professor Ray Owen in particular for training and support in production of recombinant proteins. CSR, MDS and AJP are Jenner investigators. MDS and AJP are NIHR Senior Investigators. Data sharing the authors commit to making the relevant anonymised patient level data available on reasonable request. Conflict of interest statement: AJP is Chair of UK Dept. Health and Social Care's (DHSC) Joint Committee on Vaccination & Immunisation (JCVI), and is a member of the WHO's SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. AJP, CR and CD are named inventors on a patent in the field of meningococcal vaccines. AJP waives all his rights on any patent. MDS is, or has recently been, an investigator on behalf of the University of Oxford on clinical research related to vaccines that is funded by vaccine manufacturers including Pfizer, GlaxoSmithKline, Medimmune, Novavax, Janssen, AstraZeneca and MCM vaccines. RB & AH perform contract research on behalf of UK HSA for GSK, Pfizer and Sanofi Pasteur. LB, AL, LSR, LC, KD, KF, XL, DO'C, HC and HH declare no conflict. The views expressed in this publication are those of the authors. All authors attest they meet the ICMJE criteria for authorship

Funding Information:
This work was supporting by Meningitis Research Foundation (MRF, meningitis.org), award #1702, and by the NIHR Oxford Biomedical Research Center (BRC) Vaccine theme. The funders had no role in study design, data collection, data analysis, data interpretation, writing of the report; and in the decision to submit the article for publication.

Publisher Copyright:
© 2022 The Authors

Keywords

Adolescent
Boost
Clinical trial
Memory
Meningococcus
Persistence
Vaccine

UN SDGs

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

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10.1016/j.vaccine.2022.04.085

Cite this

Rollier, C. S., Dold, C., Blackwell, L., Linder, A., Silva-Reyes, L., Clutterbuck, E., Davis, K., Ford, K., Liu, X., Holland, A., Chan, H., Harbinson, H., O'Connor, D., Borrow, R., Snape, M. D., & Pollard, A. J. (2022). Immunogenicity of a single 4CMenB vaccine booster in adolescents 11 years after childhood immunisation. Vaccine, 40(32), 4453-4463. https://doi.org/10.1016/j.vaccine.2022.04.085

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abstract = "The clinical development of the meningococcal vaccine, 4CMenB, included 2 doses in vaccine-na{\"i}ve adolescents, which was considered unlikely to be cost-effective for implementation. Theoretically, priming with 4CMenB in early childhood might drive strong immune responses after only a single booster dose in adolescents and reduce programmatic costs. To address this question, children over 11 years old who took part in previous trials involving the administration of 3–5 doses of 4CMenB at infant/preschool age from 2006 were recruited into a post licensure single-centre trial, and were divided into two groups: those who received their last dose at 12 months old (infant group) and those who received their last dose at 3 years old (infant + preschool group). Na{\"i}ve age-matched controls were randomised to receive one (adolescent 1 group) or two doses at days 0 and 28 (adolescent 2 group) of 4CMenB. Serum bactericidal antibody (SBA) assays using human complement were performed against three reference strains prior to vaccination, and at 1, 6 and 12 months. Previous vaccination was associated with a higher response to a single booster dose at 11 years of age, one-month post-vaccination, when compared with a single dose in na{\"i}ve age-matched controls. At day 180, the highest responses were observed in participants in the infant + preschool group against strain 5/99 (GMT 316.1 [CI 158.4 to 630.8]), as compared with na{\"i}ve adolescents who received two doses (GMTs 84.5 [CI 57.7 to 123.6]). When the last dose was received at 12-months of age, responses to a single adolescent dose were not as robust (GMT 61.1 [CI 14.8 to 252.4] to strain 5/99). This descriptive study indicates that the highest SBA responses after a single dose in adolescence were observed in participants who received a preschool dose, suggesting that B cell memory responses are not sufficiently primed at less than 12 months of age. Trial registration EudraCT 2017-004732-11, ISRCTN16774163.",

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author = "Rollier, {Christine S.} and Christina Dold and Luke Blackwell and Aline Linder and Laura Silva-Reyes and Elizabeth Clutterbuck and Kimberly Davis and Karen Ford and Xinxue Liu and Ann Holland and Hannah Chan and Holly Harbinson and Daniel O'Connor and Ray Borrow and Snape, {Matthew D.} and Pollard, {Andrew J.}",

note = "Funding Information: the authors thank Emma Plested, David Smith and Rachel Craik for project management, the nurses, clinical trials, IT and lab teams at the Oxford Vaccine Group for excellent work, and the participants. The authors thank the protein production facility and Professor Ray Owen in particular for training and support in production of recombinant proteins. CSR, MDS and AJP are Jenner investigators. MDS and AJP are NIHR Senior Investigators. Data sharing the authors commit to making the relevant anonymised patient level data available on reasonable request. Conflict of interest statement: AJP is Chair of UK Dept. Health and Social Care's (DHSC) Joint Committee on Vaccination & Immunisation (JCVI), and is a member of the WHO's SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. AJP, CR and CD are named inventors on a patent in the field of meningococcal vaccines. AJP waives all his rights on any patent. MDS is, or has recently been, an investigator on behalf of the University of Oxford on clinical research related to vaccines that is funded by vaccine manufacturers including Pfizer, GlaxoSmithKline, Medimmune, Novavax, Janssen, AstraZeneca and MCM vaccines. RB & AH perform contract research on behalf of UK HSA for GSK, Pfizer and Sanofi Pasteur. LB, AL, LSR, LC, KD, KF, XL, DO'C, HC and HH declare no conflict. The views expressed in this publication are those of the authors. All authors attest they meet the ICMJE criteria for authorship Funding Information: This work was supporting by Meningitis Research Foundation (MRF, meningitis.org), award #1702, and by the NIHR Oxford Biomedical Research Center (BRC) Vaccine theme. The funders had no role in study design, data collection, data analysis, data interpretation, writing of the report; and in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2022 The Authors",

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Rollier, CS, Dold, C, Blackwell, L, Linder, A, Silva-Reyes, L, Clutterbuck, E, Davis, K, Ford, K, Liu, X, Holland, A, Chan, H, Harbinson, H, O'Connor, D, Borrow, R, Snape, MD & Pollard, AJ 2022, 'Immunogenicity of a single 4CMenB vaccine booster in adolescents 11 years after childhood immunisation', Vaccine, vol. 40, no. 32, pp. 4453-4463. https://doi.org/10.1016/j.vaccine.2022.04.085

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T1 - Immunogenicity of a single 4CMenB vaccine booster in adolescents 11 years after childhood immunisation

AU - Rollier, Christine S.

AU - Dold, Christina

AU - Blackwell, Luke

AU - Linder, Aline

AU - Silva-Reyes, Laura

AU - Clutterbuck, Elizabeth

AU - Davis, Kimberly

AU - Ford, Karen

AU - Liu, Xinxue

AU - Holland, Ann

AU - Chan, Hannah

AU - Harbinson, Holly

AU - O'Connor, Daniel

AU - Borrow, Ray

AU - Snape, Matthew D.

AU - Pollard, Andrew J.

N1 - Funding Information: the authors thank Emma Plested, David Smith and Rachel Craik for project management, the nurses, clinical trials, IT and lab teams at the Oxford Vaccine Group for excellent work, and the participants. The authors thank the protein production facility and Professor Ray Owen in particular for training and support in production of recombinant proteins. CSR, MDS and AJP are Jenner investigators. MDS and AJP are NIHR Senior Investigators. Data sharing the authors commit to making the relevant anonymised patient level data available on reasonable request. Conflict of interest statement: AJP is Chair of UK Dept. Health and Social Care's (DHSC) Joint Committee on Vaccination & Immunisation (JCVI), and is a member of the WHO's SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. AJP, CR and CD are named inventors on a patent in the field of meningococcal vaccines. AJP waives all his rights on any patent. MDS is, or has recently been, an investigator on behalf of the University of Oxford on clinical research related to vaccines that is funded by vaccine manufacturers including Pfizer, GlaxoSmithKline, Medimmune, Novavax, Janssen, AstraZeneca and MCM vaccines. RB & AH perform contract research on behalf of UK HSA for GSK, Pfizer and Sanofi Pasteur. LB, AL, LSR, LC, KD, KF, XL, DO'C, HC and HH declare no conflict. The views expressed in this publication are those of the authors. All authors attest they meet the ICMJE criteria for authorship Funding Information: This work was supporting by Meningitis Research Foundation (MRF, meningitis.org), award #1702, and by the NIHR Oxford Biomedical Research Center (BRC) Vaccine theme. The funders had no role in study design, data collection, data analysis, data interpretation, writing of the report; and in the decision to submit the article for publication. Publisher Copyright: © 2022 The Authors

PY - 2022/7/30

Y1 - 2022/7/30

N2 - The clinical development of the meningococcal vaccine, 4CMenB, included 2 doses in vaccine-naïve adolescents, which was considered unlikely to be cost-effective for implementation. Theoretically, priming with 4CMenB in early childhood might drive strong immune responses after only a single booster dose in adolescents and reduce programmatic costs. To address this question, children over 11 years old who took part in previous trials involving the administration of 3–5 doses of 4CMenB at infant/preschool age from 2006 were recruited into a post licensure single-centre trial, and were divided into two groups: those who received their last dose at 12 months old (infant group) and those who received their last dose at 3 years old (infant + preschool group). Naïve age-matched controls were randomised to receive one (adolescent 1 group) or two doses at days 0 and 28 (adolescent 2 group) of 4CMenB. Serum bactericidal antibody (SBA) assays using human complement were performed against three reference strains prior to vaccination, and at 1, 6 and 12 months. Previous vaccination was associated with a higher response to a single booster dose at 11 years of age, one-month post-vaccination, when compared with a single dose in naïve age-matched controls. At day 180, the highest responses were observed in participants in the infant + preschool group against strain 5/99 (GMT 316.1 [CI 158.4 to 630.8]), as compared with naïve adolescents who received two doses (GMTs 84.5 [CI 57.7 to 123.6]). When the last dose was received at 12-months of age, responses to a single adolescent dose were not as robust (GMT 61.1 [CI 14.8 to 252.4] to strain 5/99). This descriptive study indicates that the highest SBA responses after a single dose in adolescence were observed in participants who received a preschool dose, suggesting that B cell memory responses are not sufficiently primed at less than 12 months of age. Trial registration EudraCT 2017-004732-11, ISRCTN16774163.

AB - The clinical development of the meningococcal vaccine, 4CMenB, included 2 doses in vaccine-naïve adolescents, which was considered unlikely to be cost-effective for implementation. Theoretically, priming with 4CMenB in early childhood might drive strong immune responses after only a single booster dose in adolescents and reduce programmatic costs. To address this question, children over 11 years old who took part in previous trials involving the administration of 3–5 doses of 4CMenB at infant/preschool age from 2006 were recruited into a post licensure single-centre trial, and were divided into two groups: those who received their last dose at 12 months old (infant group) and those who received their last dose at 3 years old (infant + preschool group). Naïve age-matched controls were randomised to receive one (adolescent 1 group) or two doses at days 0 and 28 (adolescent 2 group) of 4CMenB. Serum bactericidal antibody (SBA) assays using human complement were performed against three reference strains prior to vaccination, and at 1, 6 and 12 months. Previous vaccination was associated with a higher response to a single booster dose at 11 years of age, one-month post-vaccination, when compared with a single dose in naïve age-matched controls. At day 180, the highest responses were observed in participants in the infant + preschool group against strain 5/99 (GMT 316.1 [CI 158.4 to 630.8]), as compared with naïve adolescents who received two doses (GMTs 84.5 [CI 57.7 to 123.6]). When the last dose was received at 12-months of age, responses to a single adolescent dose were not as robust (GMT 61.1 [CI 14.8 to 252.4] to strain 5/99). This descriptive study indicates that the highest SBA responses after a single dose in adolescence were observed in participants who received a preschool dose, suggesting that B cell memory responses are not sufficiently primed at less than 12 months of age. Trial registration EudraCT 2017-004732-11, ISRCTN16774163.

KW - Adolescent

KW - Boost

KW - Clinical trial

KW - Memory

KW - Meningococcus

KW - Persistence

KW - Vaccine

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ER -

Immunogenicity of a single 4CMenB vaccine booster in adolescents 11 years after childhood immunisation

Abstract

Bibliographical note

Keywords

UN SDGs

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