Combination vaccines containing DTPa–Hib: impact of IPV and coadministration of CRM197 conjugates

Abstract

Vaccination with diphtheria–tetanus–acellular pertussis (DTPa)–Haemophilus influenzae type b (Hib) combinations generally elicits anti-polyribosyl-ribitol-phosphate (PRP) antibody concentrations of more than 0.15 µg/ml, a criterion that is linked to the protection of infants against Hib disease. In the UK, vaccination with DTPa3–Hib elicited atypically low anti-PRP antibody levels and was associated with breakthrough Hib cases. While the absence of a toddler booster is considered to be a key factor explaining the lowered control of Hib disease, we propose that the coadministration of serogroup C Neisseria meningitidis conjugate vaccine (MenC)–CRM197, which coincided with the introduction of DTPa3–Hib in the UK, may have played a role. However, other data suggest that the response to Hib after DTPa(HBV) inactivated polio vaccine (IPV)–Hib combinations is not affected by the coadministration of CRM197, which we postulate to be attributed to the presence of IPV. These observations underline the need to carefully evaluate upcoming pediatric conjugate vaccines for possible interference effects on the coadministered antigens, with particular attention to hepatitis B and Hib–tetanus toxoid.

Keywords::

• booster
• combination vaccine
• conjugate vaccine
• Haemophilus influenzae type b
• Hib
• immunity
• inactivated polio vaccine
• interference
• vaccine

Financial & competing interests disclosure

Jan Poolman is an employee of GlaxoSmithKline Biologicals, Rixensart, Belgium. Ron Dagan and Fred Zepp have received unrestricted grants from different vaccine manufacturers. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Infanrix is a trademark of the GlaxoSmithKline group of companies. ActHIB, Pediacel, Pentavac, Pentacel and TriHIBit are trademarks of Sanofi Aventis. Prevenar and Meningitec are trademarks of Wyeth Lederle Vaccines. Menjugate is a trademark of Novartis.

Writing assistance was utilized in the production of this manuscript. The authors thank IG Jones and investigators who conducted study 208108/029 (DTPa3-Hib in the UK), Joanne Wolter for excellent assistance with the help of Ulrike Krause and Pascal Cadot in manuscript preparation and Jeanne Jacquet, Dominique Boutriau and Lode Schuerman for expert review.