A randomised, double-blind, controlled trial of the immunogenicity and tolerability of a meningococcal group C conjugate vaccine in young British infants
Introduction
The introduction of a vaccination programme in the UK to prevent disease due to Haemophilus influenzae type B (Hib) has been extremely successful [1]. Its success is based on the ability of the polysaccharide–protein conjugate vaccine to induce effective short- [2] and long-term (memory) [3] immune responses in young infants. This success has fuelled the development of further conjugate vaccines against other leading bacterial infections. Meningococcal group C infections currently account for approximately 35% of cases of meningococcal disease in England and Wales, and disease incidence appears to be rising [4]. Trials of conjugate vaccines against this pathogen demonstrate both immunogenicity in young infants and the induction of immunologic memory [5], [6], [7], [8]. Such studies underlie the recent introduction of a programme of meningococcal group C vaccination [9] in the United Kingdom prior to an absolute demonstration of efficacy.
However, the expansion of routine immunisation programmes increases the potential for unforeseen interactions particularly as many potential new vaccines share components. In previous studies in UK infants of either Group A+C [5] or Group C only [7] meningococcal/CRM197 conjugate vaccines, there have either been no control group [5] or a Hib–tetanus conjugate vaccine has been used [7] making conjugate-related interactions impossible to examine. We now report the findings of a randomised, double-blind, controlled trial of a meningococcal group C conjugate vaccine among a group of children receiving a Hib vaccine conjugated to the same carrier. Both vaccines are licensed for use in the UK national immunisation programme. This study increases the body of data on the immunogenicity and tolerability of the new meningococcal vaccine, and allows the potential for interaction with structurally related vaccines to be examined.
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Patient population
Newborn infants registered with pre-selected, consenting general practices (comprising 31 of the 88 Oxfordshire practices) were identified from birth records at two Oxfordshire hospitals between April and November 1997. Parents of these infants were invited by letter to consider their child for inclusion in the study. Those who expressed an initial interest received further information by post, telephone and, occasionally, home visit. Infants were excluded from the study if: the birthweight was
Results
The allocation of infants and their course within the trial is given in Fig. 1. Five of the randomised infants were withdrawn from the study, three at the parents request (two hepatitis B group, one meningococcal group) and two with severe systemic adverse reactions (one hepatitis B group with inconsolable crying, one meningococcal group with fever of 40°C). There were no severe local reactions. There were no other adverse reactions thought to be probably or definitely related to vaccination.
Discussion
Three doses of a vaccine comprising the meningococcal group C oligosaccharide conjugated to CRM197 (a variant diphtheria toxoid) with an alum adjuvant produced a marked, specific IgG response when administered to 116 children at 2, 3 and 4 months of age. The geometric mean meningococcal group C antibody titre (23.9 μg/ml) was comparable with results in previous studies using similar vaccines (GMT=38.59 μg/ml [12] and 13.1 μg/ml [6]) although non-IgG-specific ELISAs were used in the these
Acknowledgements
The contributions made by the authors were as follows: Mike English, involved in design, data collection, analysis and preparation of the manuscript; Jenny MacLennan, contributed to design, data collection and preparation of the manuscript; Jane Bowen-Morris, contributed to design, data collection and preparation of the manuscript; Jon Deeks, contributed to design, analysis and preparation of the manuscript; Maggie Boardman, Jim Buttery, Karen Brown and Sandra Smith, contributed to data
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A Short History of Vaccination
2017, Plotkin's VaccinesSex-dependent immune responses to infant vaccination: An individual participant data meta-analysis of antibody and memory B cells
2016, VaccineCitation Excerpt :For studies in which infants were enrolled at two months of age or younger, the ratio of female to male infants enrolled was 0.92, broadly reflecting the sex ratio at birth in the UK which is 0.95 [29] (Table 2). Seven trials were available in which capsular group C meningococcal vaccines were administered in prime-boost combinations either as the study vaccine of interest or as a routine vaccine given concomitantly (trials #1–6, 8) [18–25,28]. Immunological parameters (immunoglobulin (IgG), serum bactericidal assay (using rabbit or human complement) (rSBA, hSBA), and memory B cells) were measured post priming (at 5 months of age) and pre- and post-boost (12 and 13 months of age).
A short history of vaccination
2012, Vaccines: Sixth EditionBaseline polysaccharide-specific antibodies may not consistently inhibit booster antibody responses in infants to a serogroup C meningococcal protein-polysaccharide conjugate vaccine
2012, VaccineCitation Excerpt :A total of 6 different vaccine schedules were used across the 5 studies (see Table 1) and the children were separated into 6 groups according to their vaccine schedule. Each dose of MenCV contained 10 μg of N. meningitidis group C oligosaccharide (MenC), however, they contained between 12.5 and 25 mcg of CRM197 [10,14–20]. They were manufactured either by Novartis Vaccines and Diagnostics (studies 1 and 3) [10 MacLennan, 2000 #36, 16], or by Wyeth Vaccines (studies 2, 4 and 5) [14,17,19].