A Phase IV Study to Evaluate the Primary and Booster Immune Responses of UK Infants Receiving a Licensed 6-in-1 DTaP/IPV/Hib/HBV Vaccine (Infanrix-HexaTM) With a 13-valent Pneumococcal Conjugate Vaccine and Incorporating a Randomisation Study of a Single Dose of 3 Different Meningococcal Group C Conjugate Vaccines at 3 Months of Age

Infants in the United Kingdom are routinely immunised against diphtheria, tetanus, pertussis (whooping cough), polio and Haemophilus influenzae type b (Hib) as a single 5-in-1 (DTaP5-IPV-Hib) combination vaccine given as a 2-3-4 month schedule. They also receive vaccines against Neisseria meningitidis serogroup C (MenC) at 3 months and against 13 pneumococcal serotypes (PCV13) at 2-4 months. From 01 July 2013, infants will also receive an oral rotavirus vaccine at 2 and 3 months of age. Combination vaccines reduce the number of injections administered to infants and, therefore, minimise the number of visits to general practitioners while, at the same time, improving compliance, parental satisfaction and the cost-effectiveness of vaccination programmes.

The development and manufacture of combination vaccines, however, is complex because of possible interactions between different antigens, carrier proteins and adjuvants used in such vaccines. Administration of Hib conjugate vaccine as part of a diphtheria-tetanus-pertussis (DTP-Hib) combination results in much lower Hib antibody concentrations compared to the Hib conjugate vaccine administered separately (Eskola et al., 1996; Schmitt et al., 1998; Schmitt et al., 2000). Similarly, the immunogenicity of the Hib component of combination vaccines containing acellular pertussis (DTaP-Hib) is significantly lower when compared to those containing whole cell pertussis (DTwP-Hib) (Bar-On et al., 2009).

Interactions can also occur between vaccines that are given during the same visit (Dagan et al., 2008, Borrow et al, 2011). Vaccines that use a diphtheria mutant toxin (CRM197) as their primary carrier protein, for example, have been shown to interfere with the immune response to the Hib component of combination vaccines in a dose-dependent manner, even when the vaccines are administered on different limbs.

On the other hand, MenC vaccines that use tetanus as their carrier protein (e.g. NeisVac-C™) may enhance immune responses to the Hib component of combination vaccines. In the UK, the current acellular-pertussis-containing 5-in-1 combination vaccine (DTaP5/Hib/IPV; Pediacel™) has been extremely effective at maintaining control of the diseases it is aiming to prevent. In particular, control of invasive Hib disease is now the best that has been achieved since the introduction of routine Hib vaccination almost 20 years ago (HPR, 2011).

IMMUNISATION AGAINST HEPATITIS B Hepatitis B virus (HBV) infection is a major global problem. HBV is highly infectious and is transmitted mainly through sexual intercourse, perinatal transmission during childbirth, injecting drug use and blood-to-blood contact (National disease surveillance centre, 1988). HBV can cause acute or chronic infection. Most of the burden of HBV infection is due to chronic infection, which may be asymptomatic for many years but is associated with an increased long-term risk of cirrhosis and hepatocellular carcinoma (Beasley, 1988).