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Immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine co-administered with a booster dose of a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine in healthy children aged 12–23 months

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Abstract

This study was undertaken to assess the co-administration of an experimental measles-mumps-rubella-varicella vaccine (MMRV, GlaxoSmithKline Biologicals) with a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate (DTPa-HBV-IPV/Hib) vaccine in healthy children. Healthy children aged 12–23 months (N = 451) were randomised to one of three parallel groups to receive one dose of MMRV vaccine co-administered with a booster dose of DTPa-HBV-IPV/Hib vaccine (co-administration group), or one dose of MMRV vaccine alone (MMRV group), or a booster dose of DTPa-HBV-IPV/Hib vaccine alone (DTPa-HBV-IPV/Hib group). No differences in seroconversion rates for measles (>95%), mumps (>80%), rubella (>99%) and varicella (>98%) were seen between the co-administration group and the MMRV group. No differences in geometric mean titres (GMTs) were observed between the two groups with the exception of anti-measles titres, which were observed to be higher in the MMRV group than in the co-administration group (4,419.2 vs. 3,441.8 mIU/ml respectively). Immune response to the booster dose of DTPa-HBV-IPV/Hib vaccine was observed to be similar in the co-administration group and the DTPa-HBV-IPV/Hib group. Co-administration of the MMRV vaccine with a booster dose of DTPa-HBV-IPV/Hib vaccine was well-tolerated and did not exacerbate the reactogenicity profile of either vaccine. In summary, GlaxoSmithKline Biologicals’ experimental MMRV vaccine was immunogenic and well-tolerated when administered with a booster dose of DTPa-HBV-IPV/Hib vaccine during the second year of life. The ability to co-administer the MMRV vaccine at the same time as other routine childhood immunisation vaccines could increase compliance with varicella vaccination in countries where this vaccine is already recommended and may facilitate implementation of varicella vaccination elsewhere.

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Abbreviations

ANCOVA:

Analysis of covariance

ANOVA:

Analysis of variance

ATP:

According to protocol

CCID:

Cell culture infective dose

CI:

Confidence interval

DTPa-HBV-IPV/Hib:

Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine

ELISA:

Enzyme-linked immunosorbent assay

FHA:

Filamentous haemagglutinin

GMT:

Geometric mean titre

HBsAg:

Hepatitis B surface antigen

MMR:

Measles-mumps-rubella

MMRV:

Measles-mumps-rubella-varicella

PRN:

Pertactin

PRP:

Polyribosyl ribitol phosphate

PT:

Pertussis toxoid

SAE:

Serious adverse event

SC:

Seroconversion

SP:

Seroprotection/seropositivity

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Acknowledgements

The authors would like to thank Dr. Markus Knuf and all the investigators who participated in this clinical trial: Drs H. Berwanger, E. Clapier, M. Collet, J. Disselhoff, J. Fleischer, F. Gamerdinger, S. Habash, U. Henke, K. Kirsten, A. Klatt, H. Krause, J. Messner, H. Preidel, L. Sander, E. Schmitz-Hauss, A. Uebing, A. Von Stuelpnagel, and B. Zu Castell-Ruedenhausen. We thank the parents and children who participated in this study and gratefully acknowledge the study nurses and other staff members. Editorial assistance in the preparation of this manuscript was provided by Jennifer Coward, B.Sc., and Catherine Arnaudeau-Bégard, Ph.D. This study [208136/013] was funded by GlaxoSmithKline Biologicals.

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Authors and Affiliations

  1. Department of Paediatrics, Johannes-Gutenberg-Universität, Langenbeckstrasse 1, 55101, Mainz, Germany

    Fred Zepp & Wilma Mannhardt-Laakmann

  2. Paediatric Office, Kehl, Germany

    Ulrich Behre

  3. Paediatric Office, Trier, Germany

    Klaus Kindler

  4. Paediatric Office, Krefeld, Germany

    Karl-Heinz Laakmann

  5. Paediatric Office, Heiligenhaus, Germany

    Heidemarie Pankow-Culot

  6. GlaxoSmithKline Biologicals, Rixensart, Belgium

    François Beckers, Dominique Descamps & Paul Willems

Authors
  1. Fred Zepp
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  2. Ulrich Behre
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  3. Klaus Kindler
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  4. Karl-Heinz Laakmann
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  5. Heidemarie Pankow-Culot
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  6. Wilma Mannhardt-Laakmann
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  7. François Beckers
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  8. Dominique Descamps
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  9. Paul Willems
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Correspondence to Fred Zepp.

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Zepp, F., Behre, U., Kindler, K. et al. Immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine co-administered with a booster dose of a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine in healthy children aged 12–23 months. Eur J Pediatr 166, 857–864 (2007). https://doi.org/10.1007/s00431-007-0506-z

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  • DOI: https://doi.org/10.1007/s00431-007-0506-z

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