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

Mildred A. Iro, Matthew D. Snape, Merryn Voysey, Sena Jawad, Adam Finn, Paul T. Heath, Gianni Bona, Susanna Esposito, Javier Diez-Domingo, Roman Prymula, Adefowope Odueyungbo, Daniela Toneatto, Peter Dull, Andrew J. Pollard, The European Men B Vaccine Study Group

Research output: Contribution to journalArticle

Abstract

Background 4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24 months and characterised the antibody response to a fifth dose administered at 4 years of age. Methods A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-naïve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-naïve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6 month schedule. Results At baseline (prior to vaccination), the proportion of participants (n = 468) with hSBA titers ⩾ 5 was similar across all followon groups: 89–100% against 5/99; 12–35% for H44/76; 8–12% for NZ98/254 and 53–80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-naïve controls (n = 206). Following a dose of 4CMenB at 4 years of age, this increased to 100% (5/99), 97–100% (H44/76), 80–95 % (NZ98/254) and 84–100% (M10713) (n = 210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-naïve controls (n = 192). Conclusion Waning of protective antibodies occurred 12–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age.

Original languageEnglish
Pages (from-to)395-402
Number of pages8
JournalVaccine
Volume35
Issue number2
DOIs
Publication statusPublished - Jan 5 2017

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administered dose
Vaccination
toddlers
Vaccines
Randomized Controlled Trials
immune response
vaccines
Appointments and Schedules
blood serum
antibodies
Antibodies
complement
dosage
Serum
vaccination
Czech Republic
Spain
Italy
Antibody Formation
Immunity

Keywords

  • 4CMenB
  • MenW
  • Neisseria meningitidis
  • Reactogenicity
  • Toddler
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

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. / Iro, Mildred A.; Snape, Matthew D.; Voysey, Merryn; Jawad, Sena; Finn, Adam; Heath, Paul T.; Bona, Gianni; Esposito, Susanna; Diez-Domingo, Javier; Prymula, Roman; Odueyungbo, Adefowope; Toneatto, Daniela; Dull, Peter; Pollard, Andrew J.; The European Men B Vaccine Study Group.

In: Vaccine, Vol. 35, No. 2, 05.01.2017, p. 395-402.

Research output: Contribution to journalArticle

Iro, MA, Snape, MD, Voysey, M, Jawad, S, Finn, A, Heath, PT, Bona, G, Esposito, S, Diez-Domingo, J, Prymula, R, Odueyungbo, A, Toneatto, D, Dull, P, Pollard, AJ & The European Men B Vaccine Study Group 2017, '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, vol. 35, no. 2, pp. 395-402. https://doi.org/10.1016/j.vaccine.2016.11.009
Iro, Mildred A. ; Snape, Matthew D. ; Voysey, Merryn ; Jawad, Sena ; Finn, Adam ; Heath, Paul T. ; Bona, Gianni ; Esposito, Susanna ; Diez-Domingo, Javier ; Prymula, Roman ; Odueyungbo, Adefowope ; Toneatto, Daniela ; Dull, Peter ; Pollard, Andrew J. ; The European Men B Vaccine Study Group. / 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. In: Vaccine. 2017 ; Vol. 35, No. 2. pp. 395-402.
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title = "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",
abstract = "Background 4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24 months and characterised the antibody response to a fifth dose administered at 4 years of age. Methods A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-na{\"i}ve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-na{\"i}ve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6 month schedule. Results At baseline (prior to vaccination), the proportion of participants (n = 468) with hSBA titers ⩾ 5 was similar across all followon groups: 89–100{\%} against 5/99; 12–35{\%} for H44/76; 8–12{\%} for NZ98/254 and 53–80{\%} for M10713 compared with 5{\%}, 0{\%}, 0{\%}; and 60{\%} respectively, for the vaccine-na{\"i}ve controls (n = 206). Following a dose of 4CMenB at 4 years of age, this increased to 100{\%} (5/99), 97–100{\%} (H44/76), 80–95 {\%} (NZ98/254) and 84–100{\%} (M10713) (n = 210), compared with 89{\%}, 70{\%}, 24{\%}, and 76{\%} respectively for vaccine-na{\"i}ve controls (n = 192). Conclusion Waning of protective antibodies occurred 12–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age.",
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author = "Iro, {Mildred A.} and Snape, {Matthew D.} and Merryn Voysey and Sena Jawad and Adam Finn and Heath, {Paul T.} and Gianni Bona and Susanna Esposito and Javier Diez-Domingo and Roman Prymula and Adefowope Odueyungbo and Daniela Toneatto and Peter Dull and Pollard, {Andrew J.} and {The European Men B Vaccine Study Group}",
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TY - JOUR

T1 - 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

AU - Iro, Mildred A.

AU - Snape, Matthew D.

AU - Voysey, Merryn

AU - Jawad, Sena

AU - Finn, Adam

AU - Heath, Paul T.

AU - Bona, Gianni

AU - Esposito, Susanna

AU - Diez-Domingo, Javier

AU - Prymula, Roman

AU - Odueyungbo, Adefowope

AU - Toneatto, Daniela

AU - Dull, Peter

AU - Pollard, Andrew J.

AU - The European Men B Vaccine Study Group

PY - 2017/1/5

Y1 - 2017/1/5

N2 - Background 4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24 months and characterised the antibody response to a fifth dose administered at 4 years of age. Methods A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-naïve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-naïve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6 month schedule. Results At baseline (prior to vaccination), the proportion of participants (n = 468) with hSBA titers ⩾ 5 was similar across all followon groups: 89–100% against 5/99; 12–35% for H44/76; 8–12% for NZ98/254 and 53–80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-naïve controls (n = 206). Following a dose of 4CMenB at 4 years of age, this increased to 100% (5/99), 97–100% (H44/76), 80–95 % (NZ98/254) and 84–100% (M10713) (n = 210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-naïve controls (n = 192). Conclusion Waning of protective antibodies occurred 12–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age.

AB - Background 4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24 months and characterised the antibody response to a fifth dose administered at 4 years of age. Methods A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-naïve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-naïve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6 month schedule. Results At baseline (prior to vaccination), the proportion of participants (n = 468) with hSBA titers ⩾ 5 was similar across all followon groups: 89–100% against 5/99; 12–35% for H44/76; 8–12% for NZ98/254 and 53–80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-naïve controls (n = 206). Following a dose of 4CMenB at 4 years of age, this increased to 100% (5/99), 97–100% (H44/76), 80–95 % (NZ98/254) and 84–100% (M10713) (n = 210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-naïve controls (n = 192). Conclusion Waning of protective antibodies occurred 12–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age.

KW - 4CMenB

KW - MenW

KW - Neisseria meningitidis

KW - Reactogenicity

KW - Toddler

KW - Vaccine

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U2 - 10.1016/j.vaccine.2016.11.009

DO - 10.1016/j.vaccine.2016.11.009

M3 - Article

AN - SCOPUS:85007015385

VL - 35

SP - 395

EP - 402

JO - Vaccine

JF - Vaccine

SN - 0264-410X

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