Safety and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine after one or two doses given to infants and toddlers

  • S. A. Halperin
  • F. Diaz-Mitoma
  • P. Dull
  • A. Anemona
  • F. Ceddia


With the emergence of multiple meningococcal serogroups in different geographic areas, broad vaccine protection from infancy is desirable. One hundred and seventy-five infants received either two doses of a meningococcal quadrivalent (A, C, W-135, Y) conjugate vaccine (MenACWY-CRM) at 6 and 12 months, one dose of MenACWY-CRM at 12 months, or MenC at 12 months and MenACWY-CRM at 18 months. Bactericidal antibody titers using human complement were measured before and 1 month after each dose. Injection-site reactions were reported by 22–45% of participants following MenACWY-CRM given at 6 or 12 months. Similar proportions of subjects had injection-site reactions following two doses of MenACWY-CRM (32–41%) or one dose of MenC (26–44%). The incidence of systemic adverse events was comparable between groups. After two doses of MenACWY-CRM, the percentages of participants reporting hSBA titers ≥8 were 100% for C, W-135, and Y, and 84% for A. Serogroup C titers were more than 10-fold higher after two doses of MenACWY-CRM than after one dose of MenC or MenACWY-CRM at 12 months. Serogroup C titers were comparable following a single dose of MenACWY-CRM or MenC at 12 months. MenACWY-CRM is well tolerated and immunogenic given at 12 months, or two doses at 6 and 12 months of age.



We thank the nurses and staff for their careful attention to detail and to the children and their families for participating in the study. We also thank Dr. Bruce Smith at the Canadian Center for Vaccinology for his independent evaluation of the statistical analysis plan and report and statistical analysis.

Financial interest

A. Anemona and P. Dull are employees of Novartis Vaccines. F. Ceddia was an employee of Novartis Vaccines; current address GlaxoSmithKline Biologicals, Rixensart, Belgium. S. Halperin and F. Diaz-Mitoma had no financial interest in the vaccine or its manufacturer, but received research funding to undertake the study.

The study was funded by Novartis Vaccines.


  1. 1.
    Erickson L, De Wals P (1998) Complications and sequelae of meningococcal disease in Quebec, Canada, 1990–1994. Clin Infect Dis 26:1159–1164CrossRefPubMedGoogle Scholar
  2. 2.
    Bilukha O, Messonnier N, Fischer M (2007) Use of meningococcal vaccines in the United States. Pediatr Infect Dis J 26(5):371–376CrossRefPubMedGoogle Scholar
  3. 3.
    Pollard AJ (2004) Global epidemiology of meningococcal disease and vaccine efficacy. Pediatr Infect Dis J 23(12 Suppl):S274–S279PubMedGoogle Scholar
  4. 4.
    Centers for Disease Control and Prevention (CDC), Active Bacterial Core Surveillence Reports, Emerging Infectious Program Network, Neisseria Meningitidis. 2005Google Scholar
  5. 5.
    World Health Organization (WHO) (1998) Control of epidemic meningococcal disease: WHO practical guidelines, 2nd edn. WHO, GenevaGoogle Scholar
  6. 6.
    MacDonald NE, Halperin SA, Law BJ, Forrest B, Danzig LE, Granoff DM (1998) Induction of immunologic memory by conjugated vs. plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial. JAMA 280:1685–1689CrossRefPubMedGoogle Scholar
  7. 7.
    Gold R, Lepow ML, Goldschneider I, Draper TL, Gotschlich EC (1975) Clinical evaluation of group A and group C meningococcal polysaccharide vaccines in infants. J Clin Invest 56:1536–1547CrossRefPubMedGoogle Scholar
  8. 8.
    Snape MD, MacLennan JM, Lockhart S, English M, Yu L-M, Moxon RE, Pollard AJ (2009) Demonstration of immunologic memory using serogroup C meningococcal glycoconjugate vaccine. Pediatr Infect Dis J 28:92–97CrossRefPubMedGoogle Scholar
  9. 9.
    Heath PT (1998) Haemophilus influenzae type b conjugate vaccines: a review of efficacy data. Pediatr Infect Dis J 17:S117–S122CrossRefPubMedGoogle Scholar
  10. 10.
    Snape MD, Pollard AJ (2005) Meningococcal polysaccharide-protein conjugate vaccines. Lancet Infect Dis 5(1):21–30CrossRefPubMedGoogle Scholar
  11. 11.
    Booy R, Jelfs J, El Bashir H, Nissen MD (2007) Impact of meningococcal C conjugate vaccine use in Australia. Med J Aust 186(3):108–109PubMedGoogle Scholar
  12. 12.
    Larrauri A, Cano R, García M, de Mateo S (2005) Impact and effectiveness of meningococcal C conjugate vaccine following its introduction in Spain. Vaccine 23:4097–4100CrossRefPubMedGoogle Scholar
  13. 13.
    Centers for Disease Control and Prevention (CDC) (2007) Revised recommendations of the Advisory Committee on Immunization Practices to vaccinate all persons aged 11–18 years with meningococcal conjugate vaccine. MMWR Morb Mortal Wkly Rep 56:794–795Google Scholar
  14. 14.
    Rennels M, King J Jr, Ryall R, Papa T, Froeschle J (2004) Dosage escalation, safety and immunogenicity study of four dosages of a tetravalent meninogococcal polysaccharide diphtheria toxoid conjugate vaccine in infants. Pediatr Infect Dis J 23:429–435CrossRefPubMedGoogle Scholar
  15. 15.
    Vu DM, Welsch JA, Zuno-Mitchell P, Dela Cruz JV, Granoff DM (2006) Antibody persistence 3 years after immunization of adolescents with quadrivalent meningococcal conjugate vaccine. J Infect Dis 193:821–828CrossRefPubMedGoogle Scholar
  16. 16.
    Goldschneider I, Gotschlich EC, Artenstein MS (1969) Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med 129:1307–1326CrossRefPubMedGoogle Scholar
  17. 17.
    Snape M, Perrett K, Ford KJ, John TM, Pace D, Yu LM, Langley JM, McNeil S, Dull PM, Ceddia F, Anemona A, Halperin SA, Dobson S, Pollard AJ (2008) Immunogenicity of a tetravalent meningococcal glycoconjugate vaccine in infants: a randomized controlled trial. JAMA 299:173–184CrossRefPubMedGoogle Scholar
  18. 18.
    Perrett KP, Snape MD, Ford KJ, John TM, Yu LM, Langley JM, McNeil S, Dull PM, Ceddia F, Anemona A, Halperin SA, Dobson S, Pollard AJ (2009) Immunogenicity and immune memory of a nonadjuvanted quadrivalent meningococcal glycoconjugate vaccine in infants. Pediatr Infect Dis J 28:186–193CrossRefPubMedGoogle Scholar
  19. 19.
    Centers for Disease Control and Prevention (CDC) (2007) Notice to Readers: Recommendation from the Advisory Committee on Immunization Practices (ACIP) for use of quadrivalent meningococcal conjugate vaccine (MCV4) in children aged 2–10 years at increased risk for invasive meningococcal disease. MMWR Morb Mortal Wkly Rep 56:1265–1266Google Scholar
  20. 20.
    Public Health Agency of Canada. Publicly funded immunization programs in Canada—routine schedule for infants and children (including special programs and catch-up programs). Available online at: Accessed 17 February 2009
  21. 21.
    Trotter CL, Edmunds WJ, Ramsay ME, Miller E (2006) Modeling future changes to the meningococcal serogroup C conjugate (MCC) vaccine program in England and Wales. Hum Vaccin 2:68–73PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • S. A. Halperin
    • 1
  • F. Diaz-Mitoma
    • 2
  • P. Dull
    • 3
  • A. Anemona
    • 3
  • F. Ceddia
    • 3
  1. 1.Clinical Trials Research Center, Canadian Center for VaccinologyDalhousie University and the IWK Health CentreHalifaxCanada
  2. 2.Children’s Hospital of Eastern OntarioOttawaCanada
  3. 3.Novartis VaccinesSienaItaly

Personalised recommendations