Elsevier

Vaccine

Volume 25, Issue 51, 12 December 2007, Pages 8487-8499
Vaccine

A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus-toxoid conjugate vaccine is immunogenic and induces immune memory when co-administered with DTPa-HBV-IPV and conjugate pneumococcal vaccines in infants

https://doi.org/10.1016/j.vaccine.2007.10.013Get rights and content

Abstract

Immunogenicity and safety of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus-toxoid conjugate vaccine (Hib-MenCY-TT) candidate was evaluated when co-administered with DTPa-HBV-IPV(Pediarix3) + PCV7(Prevnar4) at 2–4–6 months of age. Anti-PRP concentrations ≥1.0 μg/mL were observed in 92.9–98.7%, rSBA-MenC/Y titres ≥1:8 in >98%, rSBA-MenC/Y titres ≥1:128 in >95.8 and >89.9% subjects. PRP and MenC responses were similar to respective controls (ActHIB5 and Menjugate6) including for antibody persistence. Response to co-administered vaccines was not impaired. Polysaccharide challenge (PRP, PSC, PSY at 11–14 months of age) evidenced immune memory was induced for Hib, MenC/Y conjugate components. The safety profile of Hib-MenCY-TT was similar to controls. Hib-MenCY-TT administered according to the current US Hib vaccine schedule has the potential to induce protective antibodies against Hib and meningococcal-CY disease in infants and toddlers.

Introduction

In the United States (US) there are between 2400 and 3000 cases of meningococcal disease each year, with an approximate incidence of 1.0/100,000 [1], [2]. During the last decade the proportion of meningococcal disease due to serogroup Y has risen from 2% in 1990–1992 to 39 and 22% in the period between 1996–2001 and 2001–2005, respectively [2], [3], [4], [5]. In the same periods serogroup C accounted for 31 and 26% of cases overall [2], [5], making serogroups C and Y together the cause of approximately half of the cases of meningococcal disease in the US. Most of the remaining cases are caused by serogroup B meningococci. Elsewhere in the world, serogroup C is an important cause of disease although it became less common in those countries where a meningococcal C conjugate vaccine has been introduced [6].

In the US, the incidence of meningococcal disease peaks during the first year of life, where serogroups C and Y together account for approximately half of the cases [1]. It is estimated that a combined CY conjugate vaccine administered to infants would, over time, prevent 48% more meningococcal cases than a monovalent serogroup C vaccine [4]. The monovalent meningococcal serogroup C conjugate vaccines existing for use in infants in most developed countries are not available in the US. A MenCY conjugate vaccine would be optimally developed as a combination with existing vaccines for infants, to avoid additional injections in this age group. A licensed meningococcal ACWY conjugate vaccine was introduced in the routine immunization program in the US for 11–12-year-old children but is poorly immunogenic in infancy [7].

Three formulations of a novel combined Haemophilus influenzae type b-N. meningitidis serogroup C and Y vaccine conjugated to tetanus-toxoid (Hib-MenCY-TT) for the primary vaccination of infants were evaluated. To simultaneously evaluate possible co-administration effects, the study vaccine was administered concomitantly with routinely administered, licensed vaccines. Antibody persistence after primary vaccination was assessed at 11–14 months of age and, immune memory was assessed by immunization with 10 μg of each plain Hib, MenC and MenY polysaccharides.

Section snippets

Study design

This randomized study was performed at three sites in Australia between March 2003 and August 2004 and was conducted according to Good Clinical Practice guidelines and the Declaration of Helsinki (South Africa). Protocols were approved by the ethics review committees of the participating centers. Written informed consent was obtained from parents/guardians prior to enrolment. Three different formulations of the Hib-MenCY-TT conjugate vaccine were evaluated. The MenC immune response was compared

Results

A total of 409 subjects were enrolled and randomized in the primary phase between March 2003 and February 2004 and 407 subjects received vaccine. Three hundred and ninety-four subjects participated in the challenge phase of the study from December 2003 to August 2004 (Fig. 2). All groups were comparable in terms of demographic characteristics: the mean age of the total vaccinated cohort at the time of the first vaccination and at the time of the booster vaccination was, respectively, 8.1 weeks

Discussion

The novel Hib-MenCY-TT conjugate vaccine reported here is the first candidate vaccine that combines Hib antigen with conjugated MenC and MenY antigens. The goal in developing this product was to provide a vaccine for infants against two of the major serogroups contributing to meningococcal disease in infants in the US and other countries where MenY may become endemic in the future.

The MenY component in this vaccine resulted in the development of bactericidal antibodies in at least 98% of

Acknowledgements

This clinical trial was registered at ClinicalTrials.gov (www.clinicaltrials.gov) under registration number NCT00127855. The authors thank all the infants and their families as well as the health care personnel who participated in this study. The authors thank Dr. Jim Buttery, Dale Cooper, Susie Gabriel, Marita Kefford, Kerry-Ann O’Grady, Jacinta O'Sullivan and all other research nurses, phlebotomists and study doctors from the Murdoch Children's Research Institute and School of Population

References (34)

  • A. Pollard

    Global epidemiology of meningococcal disease and vaccine efficacy

    Pediatr Infect Dis J

    (2004)
  • H.L. Keyserling et al.

    Experience with MCV-4, a meningococcal, diphtheria toxoid conjugate vaccine against serogroups A, C, Y and W-135

    Expert Rev Vaccines

    (2006)
  • Pediarix™ Summary of Product...
  • S.E. Maslanka et al.

    Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays

    Clin Diagn Lab Immunol

    (1997)
  • L.L. Gheesling et al.

    Multicenter comparison of Neisseria meningitidis serogroup C anti-capsular polysaccharide antibody levels measured by a standardized enzyme-linked immunosorbent assay

    J Clin Microbiol

    (1994)
  • World Health Organization. Guidelines for WHO/EPI Collaborative Studies on Poliomyelitis-Standard Procedure for...
  • N. Concepcion et al.

    Pneumococcal type 22F polysaccharide absorption improves the specificity of a pneumococcal-polysaccharide enzyme-linked immunosorbent assay

    Clin Diagn Lab Immunol

    (2001)
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    These results were presented in preliminary form at the annual meeting of the Pediatric Academic Societies (PAS), San Francisco, USA, April 29–May 2, 2006.

    1

    DR is now Division of Health Sciences, University of Otago, New Zealand.

    2

    Tel.: +32 2 656 9120; fax: +32 2 656 8044.

    3

    Pediarix is the Trademark of the GlaxoSmithKline group of companies.

    4

    Prevnar is the Trademark of Wyeth.

    5

    ActHIB is the Trademark of Sanofi Pasteur.

    6

    Menjugate is the Trademark of Novartis.

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