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Clinical and Vaccine Immunology, October 2007, p. 1362-1369, Vol. 14, No. 10
1071-412X/07/$08.00+0     doi:10.1128/CVI.00154-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Quality of the Haemophilus influenzae Type b (Hib) Antibody Response Induced by Diphtheria-Tetanus-Acellular Pertussis/Hib Combination Vaccines{triangledown}

Philippe A. Denoël,1 David Goldblatt,2 Isabel de Vleeschauwer,1 Jeanne-Marie Jacquet,1 Michael E. Pichichero,3 and Jan T. Poolman1*

GlaxoSmithKline Biologicals, Rue de l'institut 89, Rixensart 1330, Belgium,1 Institute of Child Health, University College London, London, United Kingdom,2 University of Rochester Medical Center, Rochester, New York3

Received 11 April 2007/ Returned for modification 30 May 2007/ Accepted 6 August 2007

It has been repeatedly observed that mixing Haemophilus influenzae type b (Hib) conjugate vaccines with acellular pertussis-containing vaccines (diphtheria-tetanus-acellular pertussis [DTPa]) resulted in a reduced magnitude of the anti-polyriboseribitolphosphate antibody response compared to that obtained when Hib vaccines were administered separately and not mixed. Nevertheless, the quality and functionality of the immune responses have been shown to be the same. With the purpose of investigating the quality of the anti-Hib immune responses that are elicited under different vaccination regimens, we report here four primary and booster-based pediatric clinical trials in which Hib vaccine was either mixed with DTPa or diphtheria-tetanus-whole-cell pertussis (DTPw)-based vaccines or was coadministered. Our results show that avidity maturation of the antibodies was lower when primary vaccination involved DTPa mixed with Hib compared to when DTPa and Hib were coadministered. No such difference was observed between mixed and separately administered Hib when associated with DTPa-hepatitis B virus-inactivated poliovirus or DTPw-based vaccines. All different combinations and regimens elicited the same opsonophagocytic and bactericidal activity as well as the same ability to protect in a passive infant rat protection assay. The functional activity of mixed DTPa-based and Hib vaccines was similar to that of mixed DTPw-based/Hib combinations. In conclusion, in vitro and in vivo data as well as postmarketing vaccine effectiveness data attest to the ability of DTPa-based/Hib combination vaccines to effectively prevent Hib-induced disease in children.

* Corresponding author. Mailing address: GlaxoSmithKline Biologicals, Rue de l'Institut 89, 1330 Rixensart, Belgium. Phone: 32 2 656 9847. Fax: 32 2 656 8113. E-mail: Jan.Poolman{at}gskbio.com

{triangledown} Published ahead of print on 15 August 2007.

Clinical and Vaccine Immunology, October 2007, p. 1362-1369, Vol. 14, No. 10
1071-412X/07/$08.00+0     doi:10.1128/CVI.00154-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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