Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules

A randomized controlled trial

Nicoletta Gossger, Matthew D. Snape, Ly Mee Yu, Adam Finn, Gianni Bona, Susanna Esposito, Nicola Principi, Javier Diez-Domingo, Etienne Sokal, Birgitta Becker, Dorothee Kieninger, Roman Prymula, Peter Dull, Ellen Ypma, Daniela Toneatto, Alan Kimura, Andrew J. Pollard

Research output: Contribution to journalArticle

210 Citations (Scopus)

Abstract

Context: In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries. Objective: To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately. Design, Setting, and Participants: Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe. Intervention: Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months. Main Outcome Measures: Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99). Results: After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together. Conclusion: A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations. Trial Registration: clinicaltrials.gov Identifier: NCT00721396.

Original languageEnglish
Pages (from-to)573-582
Number of pages10
JournalJournal of the American Medical Association
Volume307
Issue number6
DOIs
Publication statusPublished - Feb 8 2012

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Meningococcal Vaccines
Immunization Schedule
Vaccination
Vaccines
Randomized Controlled Trials
Serogroup
Haemophilus Vaccines
Serogroup B Neisseria meningitidis
Antigens
Haemophilus influenzae type b
Diphtheria
Whooping Cough
Tetanus
Poliomyelitis
Hepatitis B

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules : A randomized controlled trial. / Gossger, Nicoletta; Snape, Matthew D.; Yu, Ly Mee; Finn, Adam; Bona, Gianni; Esposito, Susanna; Principi, Nicola; Diez-Domingo, Javier; Sokal, Etienne; Becker, Birgitta; Kieninger, Dorothee; Prymula, Roman; Dull, Peter; Ypma, Ellen; Toneatto, Daniela; Kimura, Alan; Pollard, Andrew J.

In: Journal of the American Medical Association, Vol. 307, No. 6, 08.02.2012, p. 573-582.

Research output: Contribution to journalArticle

Gossger, N, Snape, MD, Yu, LM, Finn, A, Bona, G, Esposito, S, Principi, N, Diez-Domingo, J, Sokal, E, Becker, B, Kieninger, D, Prymula, R, Dull, P, Ypma, E, Toneatto, D, Kimura, A & Pollard, AJ 2012, 'Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: A randomized controlled trial', Journal of the American Medical Association, vol. 307, no. 6, pp. 573-582. https://doi.org/10.1001/jama.2012.85
Gossger, Nicoletta ; Snape, Matthew D. ; Yu, Ly Mee ; Finn, Adam ; Bona, Gianni ; Esposito, Susanna ; Principi, Nicola ; Diez-Domingo, Javier ; Sokal, Etienne ; Becker, Birgitta ; Kieninger, Dorothee ; Prymula, Roman ; Dull, Peter ; Ypma, Ellen ; Toneatto, Daniela ; Kimura, Alan ; Pollard, Andrew J. / Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules : A randomized controlled trial. In: Journal of the American Medical Association. 2012 ; Vol. 307, No. 6. pp. 573-582.
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abstract = "Context: In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries. Objective: To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately. Design, Setting, and Participants: Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe. Intervention: Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months. Main Outcome Measures: Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99). Results: After three 4CMenB vaccinations, 99{\%} or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79{\%} (95{\%} CI, 75.2{\%}-82.4{\%}) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1{\%} (95{\%} CI, 82.9{\%}-89.0{\%}) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7{\%} (95{\%} CI, 76.6{\%}-86.2{\%}) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26{\%} (158/602) to 41{\%} (247/607) of 4CMenB doses when administered alone, compared with 23{\%} (69/304) to 36{\%} (109/306) after routine vaccines given alone and 51{\%} (306/605) to 61{\%} (380/624) after 4CMenB and routine vaccines administered together. Conclusion: A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations. Trial Registration: clinicaltrials.gov Identifier: NCT00721396.",
author = "Nicoletta Gossger and Snape, {Matthew D.} and Yu, {Ly Mee} and Adam Finn and Gianni Bona and Susanna Esposito and Nicola Principi and Javier Diez-Domingo and Etienne Sokal and Birgitta Becker and Dorothee Kieninger and Roman Prymula and Peter Dull and Ellen Ypma and Daniela Toneatto and Alan Kimura and Pollard, {Andrew J.}",
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TY - JOUR

T1 - Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules

T2 - A randomized controlled trial

AU - Gossger, Nicoletta

AU - Snape, Matthew D.

AU - Yu, Ly Mee

AU - Finn, Adam

AU - Bona, Gianni

AU - Esposito, Susanna

AU - Principi, Nicola

AU - Diez-Domingo, Javier

AU - Sokal, Etienne

AU - Becker, Birgitta

AU - Kieninger, Dorothee

AU - Prymula, Roman

AU - Dull, Peter

AU - Ypma, Ellen

AU - Toneatto, Daniela

AU - Kimura, Alan

AU - Pollard, Andrew J.

PY - 2012/2/8

Y1 - 2012/2/8

N2 - Context: In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries. Objective: To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately. Design, Setting, and Participants: Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe. Intervention: Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months. Main Outcome Measures: Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99). Results: After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together. Conclusion: A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations. Trial Registration: clinicaltrials.gov Identifier: NCT00721396.

AB - Context: In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries. Objective: To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately. Design, Setting, and Participants: Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe. Intervention: Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months. Main Outcome Measures: Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99). Results: After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together. Conclusion: A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations. Trial Registration: clinicaltrials.gov Identifier: NCT00721396.

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