Elsevier

Vaccine

Volume 19, Issues 9–10, 8 December 2000, Pages 1232-1238
Vaccine

A randomised, double-blind, controlled trial of the immunogenicity and tolerability of a meningococcal group C conjugate vaccine in young British infants

https://doi.org/10.1016/S0264-410X(00)00241-3Get rights and content

Abstract

A double-blind, randomised, controlled trial was conducted in 248 British infants to assess the immunogenicity and tolerability of three doses of a meningococcal group C/CRM 197 conjugate vaccine (Lederle Laboratories, USA) given at 2, 3 and 4 months. Control children received three doses of Hepatitis B vaccine (Engerix B®; SmithKline Beecham). At 5 months of age, 100% of children receiving the conjugate vaccine had specific immunoglobulin G concentrations >2.0 μg/ml (n=116) compared with only 4% of control children (n=121). Those receiving the conjugate also had 2.5- and 1.6-fold higher geometric mean concentrations of PRP and diphtheria antibodies, respectively. The vaccine was well tolerated.

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.

Section snippets

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

References (20)

  • R. Booy et al.

    Efficacy of Haemophilus Influenzae type b conjugate vaccine PRP-T

    The Lancet

    (1994)
  • P.G.D. Kriz et al.

    Microevolution through DNA exchange among strains of Neisseria meningitidis isolated during an outbreak in the Czech Republic

    Res. Microbiol.

    (1999)
  • Salisbury DM, Begg, NT. Immunisation against Infectious Disease. Department of Health, London, UK,...
  • R. Booy et al.

    Immunogenicity and safety of the PRP-T conjugate vaccinegiven according to the British accelerated immunisation schedule

    Arch. Dis. Childhood

    (1992)
  • Communicable Disease Report. PHLS Communicable Disease Surveillance Centre,...
  • E.C. Gotschlich et al.

    Quantitative determination of the human immune response to immunization with meningococcal vaccines

    J. Clin. Invest.

    (1972)
  • P.B.R. Richmond et al.

    Meningococcal serogroup C conjugate vaccine is immunogenic in infancy and primes for memory

    J. Infect. Dis.

    (1999)
  • J. MacLennan et al.

    Safety, immunogenicity, and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants

    J. Am. Med. Assoc.

    (2000)
  • G. Campagne et al.

    Safety and Immunogenicity of three doses of a Neisseria Meningitidis A+C diptheria conjugate vaccine in infants from Niger

    Pediatr. Infect. Dis. J.

    (2000)
  • Chief Medical Officer. Introduction of Immunisation against Group C Meningococcal Infection. Chief Medical Officer, UK,...
There are more references available in the full text version of this article.

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