Skip to main content

Meningococcal Quadrivalent Tetanus Toxoid Conjugate Vaccine (MenACWY-TT; Nimenrix®): A Review

Abstract

MenACWY-TT (Nimenrix®) is a quadrivalent meningococcal tetanus toxoid conjugate vaccine licensed in Europe for active immunisation of individuals aged ≥ 6 weeks against invasive disease caused by Neisseria meningitidis capsular groups A, C, W and Y. MenACWY-TT is the first quadrivalent conjugate vaccine to be approved in Europe for use in infants as young as 6 weeks of age. Numerous phase II–IIIb clinical studies showed that intramuscular MenACWY-TT administered as primary or booster vaccination was highly immunogenic for all four vaccine capsular groups and had an acceptable reactogenicity profile in individuals aged 6 weeks to ≥ 56 years. MenACWY-TT is as immunogenic and safe as other previously licensed monovalent capsular group C or quadrivalent capsular groups A, C, W and Y meningococcal vaccines and can be coadministered with other routine vaccines without adversely affecting the immunogenicity or safety profiles of either vaccine. Current data indicate that primary and booster vaccination with MenACWY-TT is a valuable and safe option for broadening meningococcal protection against four capsular groups across a broad age range, starting as early as 6 weeks of age.

This is a preview of subscription content, access via your institution.

References

  1. WHO. Meningococcal meningitis: fact sheet no. 141. 2017. http://www.who.int/mediacentre/factsheets/fs141/en/. Accessed 13 Oct 2017.

  2. Jafri RZ, Ali A, Messonnier NE, et al. Global epidemiology of invasive meningococcal disease. Popul Health Metr. 2013;11(1):17.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Harrison OB, Claus H, Jiang Y, et al. Description and nomenclature of Neisseria meningitidis capsule locus. Emerg Infect Dis. 2013;19(4):566–73.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Pelton SI. The global evolution of meningococcal epidemiology following the introduction of meningococcal vaccines. J Adolesc Health. 2016;59(2 Suppl):S3–11.

    Article  PubMed  Google Scholar 

  5. Centers for Disease Control and Prevention. Active bacterial core surveillance (ABCs) report emerging infections program network: Neisseria meningitidis. 2015. https://www.cdc.gov/abcs/reports-findings/survreports/mening15.pdf. Accessed 13 Oct 2017.

  6. Abio A, Neal KR, Beck CR. An epidemiological review of changes in meningococcal biology during the last 100 years. Pathog Glob Health. 2013;107(7):373–80.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Broker M, Jacobsson S, Kuusi M, et al. Meningococcal serogroup Y emergence in Europe: update 2011. Hum Vaccin Immunother. 2012;8(12):1907–11.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ladhani SN, Beebeejaun K, Lucidarme J, et al. Increase in endemic Neisseria meningitidis capsular group W sequence type 11 complex associated with severe invasive disease in England and Wales. Clin Infect Dis. 2015;60(4):578–85.

    CAS  Article  PubMed  Google Scholar 

  9. Assaf-Casals A, Dbaibo G. Meningococcal quadrivalent tetanus toxoid conjugate vaccine (MenACWY-TT, Nimenrix™): a review of its immunogenicity, safety, co-administration, and antibody persistence. Hum Vaccin Immunother. 2016;12(7):1825–37.

    PubMed  PubMed Central  Google Scholar 

  10. Peltola H, Kayhty H, Kuronen T, et al. Meningococcus group A vaccine in children three months to five years of age. Adverse reactions and immunogenicity related to endotoxin content and molecular weight of the polysaccharide. J Pediatr. 1978;92(5):818–22.

    CAS  Article  PubMed  Google Scholar 

  11. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet. 2007;369(9580):2196–210.

    Article  PubMed  Google Scholar 

  12. Dellicour S, Greenwood B. Systematic review: impact of meningococcal vaccination on pharyngeal carriage of meningococci. Trop Med Int Health. 2007;12(12):1409–21.

    Article  PubMed  Google Scholar 

  13. Pichichero ME. Protein carriers of conjugate vaccines: characteristics, development, and clinical trials. Hum Vaccin Immunother. 2013;9(12):2505–23.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. European Medicines Agency. Nimenrix: summary of product characteristics. 2017. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002226/WC500127663.pdf. Accessed 13 Oct 2016.

  15. Pfizer Inc. Pfizer receives approval in the European Union for Nimenrix™ (meningococcal group A, C, W-135, and Y conjugate vaccine) in infants six weeks of age and older [media release]. 19 Dec 2016. http://press.pfizer.com/press-release/pfizer-receives-approval-european-union-nimenrix-meningococcal-group-c-w-135-and-y-con.

  16. Abdelhameed AS, Morris GA, Almutairi F, et al. Solution conformation and flexibility of capsular polysaccharides from Neisseria meningitidis and glycoconjugates with the tetanus toxoid protein. Sci Rep. 2016;6:35588.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. European Medicines Agency. Nimenrix: assessment report (EMEA/H/C/000113/P46/0017). 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/002226/WC500144738.pdf. Accessed 13 Oct 2017.

  18. Borrow R, Balmer P, Miller E. Meningococcal surrogates of protection: serum bactericidal antibody activity. Vaccine. 2005;23(17–18):2222–7.

    CAS  Article  PubMed  Google Scholar 

  19. Andrews N, Borrow R, Miller E. Validation of serological correlate of protection for meningococcal C conjugate vaccine by using efficacy estimates from postlicensure surveillance in England. Clin Diagn Lab Immunol. 2003;10(5):780–6.

    PubMed  PubMed Central  Google Scholar 

  20. Merino Arribas JM, Carmona Martinez A, Horn M, et al. Safety and immunogenicity of the quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine co-administered with routine childhood vaccines in European infants: an open, randomized trial. Pediatr Infect Dis J. 2016;36(4):e98–107.

    Article  Google Scholar 

  21. European Medicines Agency. Nimenrix: assessment report (EMEA/H/C/002226/II/0049). 2016. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/002226/WC500220577.pdf. Accessed 13 Oct 2017.

  22. Vesikari T, Karvonen A, Bianco V, et al. Tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine is well tolerated and immunogenic when co-administered with measles-mumps-rubella-varicella vaccine during the second year of life: an open, randomized controlled trial. Vaccine. 2011;29(25):4274–84.

    CAS  Article  PubMed  Google Scholar 

  23. Knuf M, Pantazi-Chatzikonstantinou A, Pfletschinger U, et al. An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children. Vaccine. 2011;29(25):4264–73.

    CAS  Article  PubMed  Google Scholar 

  24. Klein NP, Baine Y, Bianco V, et al. One or two doses of quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine is immunogenic in 9- to 12-month-old children. Pediatr Infect Dis J. 2013;32(7):760–7.

    Article  PubMed  Google Scholar 

  25. GlaxoSmithKline. 116892 scientific result summary. 2016. https://www.gsk-clinicalstudyregister.com/files2/116892%20-%20Clinical-Study-Result-Summary.pdf. Accessed 13 Oct 2017.

  26. Gill CJ, Ram S, Welsch JA, et al. Correlation between serum bactericidal activity against Neisseria meningitidis serogroups A, C, W-135 and Y measured using human versus rabbit serum as the complement source. Vaccine. 2011;30(1):29–34.

    CAS  Article  PubMed  Google Scholar 

  27. Bona G, Castiglia P, Zoppi G, et al. Safety and immunogenicity of a CRM or TT conjugated meningococcal vaccine in healthy toddlers. Vaccine. 2016;34(29):3363–70.

    CAS  Article  PubMed  Google Scholar 

  28. Memish ZA, Dbaibo G, Montellano M, et al. Immunogenicity of a single dose of tetravalent meningococcal serogroups A, C, W-135, and Y conjugate vaccine administered to 2- to 10-year-olds is noninferior to a licensed-ACWY polysaccharide vaccine with an acceptable safety profile. Pediatr Infect Dis J. 2011;30(4):e56–62.

    Article  PubMed  Google Scholar 

  29. Knuf M, Romain O, Kindler K, et al. Immunogenicity and safety of the quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) in 2-10-year-old children: results of an open, randomised, controlled study. Eur J Pediatr. 2013;172(5):601–12.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Bermal N, Huang LM, Dubey AP, et al. Safety and immunogenicity of a tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine in adolescents and adults. Hum Vaccin. 2011;7(2):239–47.

    CAS  Article  PubMed  Google Scholar 

  31. Dbaibo G, El-Ayoubi N, Ghanem S, et al. Immunogenicity and safety of a quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) administered to adults aged 56 years and older: results of an open-label, randomized, controlled trial. Drugs Aging. 2013;30(5):309–19.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Dbaibo G, Macalalad N, Aplasca-De Los Reyes MR, et al. The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine: a randomized, controlled non-inferiority study. Hum Vaccin Immunother. 2012;8(7):873–80.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. Baxter R, Baine Y, Kolhe D, et al. Five-year antibody persistence and booster response to a single dose of meningococcal A, C, W and Y tetanus toxoid conjugate vaccine in adolescents and young adults: an open, randomized trial. Pediatr Infect Dis J. 2015;34(11):1236–43.

    Article  PubMed  Google Scholar 

  34. Vesikari T, Forsten A, Bianco V, et al. Antibody persistence up to 5 years after vaccination of toddlers and children between 12 months and 10 years of age with a quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine. Hum Vaccin Immunother. 2016;12(1):132–9.

    Article  PubMed  Google Scholar 

  35. Klein NP, Baine Y, Kolhe D, et al. Five-year antibody persistence and booster response after 1 or 2 doses of meningococcal A, C, W and Y tetanus toxoid conjugate vaccine in healthy children. Pediatr Infect Dis J. 2016;35(6):662–72.

    Article  PubMed  Google Scholar 

  36. Knuf M, Baine Y, Bianco V, et al. Antibody persistence and immune memory 15 months after priming with an investigational tetravalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) in toddlers and young children. Hum Vaccin Immunother. 2012;8(7):866–72.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Vesikari T, Forsten A, Bianco V, et al. Immunogenicity, safety and antibody persistence of a booster dose of quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine compared with monovalent meningococcal serogroup C vaccine administered four years after primary vaccination using the same vaccines. Pediatr Infect Dis J. 2015;34(12):e298–307.

    Article  PubMed  Google Scholar 

  38. GlaxoSmithKline. 113977 scientific result summary. 2015. https://www.gsk-clinicalstudyregister.com/files2/d0424121-e9e2-4274-8b5d-887bcb757aad. Accessed 13 Oct 2017.

  39. Baxter R, Baine Y, Ensor K, et al. Immunogenicity and safety of an investigational quadrivalent meningococcal ACWY tetanus toxoid conjugate vaccine in healthy adolescents and young adults 10 to 25 years of age. Pediatr Infect Dis J. 2011;30(3):e41–8.

    Article  PubMed  Google Scholar 

  40. Ishola DA, Andrews N, Waight P, et al. Randomized trial to compare the immunogenicity and safety of a CRM or TT conjugated quadrivalent meningococcal vaccine in teenagers who received a CRM or TT conjugated serogroup C vaccine at preschool age. Pediatr Infect Dis J. 2015;34(8):865–74.

    Article  PubMed  Google Scholar 

  41. Public Health England. Meningococcal ACWY immunisation programme for adolescents: information for healthcare professionals. 2016. https://www.gov.uk/government/publications/menacwy-programme-information-for-healthcare-professionals. Accessed 13 Oct 2017.

  42. Read RC, Baxter D, Chadwick DR, et al. Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial. Lancet. 2014;384(9960):2123–31.

    CAS  Article  PubMed  Google Scholar 

  43. Dbaibo G, Van der Wielen M, Reda M, et al. The tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic with a clinically acceptable safety profile in subjects previously vaccinated with a tetravalent polysaccharide vaccine. Int J Infect Dis. 2012;16(8):e608–15.

    CAS  Article  PubMed  Google Scholar 

  44. Østergaard L, Silfverdal SA, Berglund J, et al. A tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when co-administered with Twinrix® in subjects aged 11-17 years: an open, randomised, controlled trial. Vaccine. 2012;30(4):774–83.

    Article  PubMed  Google Scholar 

  45. Aplasca-De Los Reyes MR, Dimaano E, Macalalad N, et al. The investigational meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine (ACWY-TT) and the seasonal influenza virus vaccine are immunogenic and well-tolerated when co-administered in adults. Hum Vaccin Immunother. 2012;8(7):881–7.

    CAS  Article  PubMed  Google Scholar 

  46. Ruiz-Palacios GM, Huang LM, Lin TY, et al. Immunogenicity and safety of a booster dose of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine coadministered with the tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in toddlers: a randomized trial. Pediatr Infect Dis J. 2013;32(1):62–71.

    Article  PubMed  Google Scholar 

  47. European Centre for Disease Prevention and Control. Vaccine schedule: recommended immunisations for meningococcal disease. 2017. http://vaccine-schedule.ecdc.europa.eu/Pages/Scheduler.aspx. Accessed 13 Oct 2017.

  48. Public Health England. Meningococcal: the green book, chapter 22. 2016. https://www.gov.uk/government/publications/meningococcal-the-green-book-chapter-22. Accessed 13 Oct 2017.

  49. Borrow R, Alarcon P, Carlos J, et al. The Global Meningococcal Initiative: global epidemiology, the impact of vaccines on meningococcal disease and the importance of herd protection. Expert Rev Vaccines. 2017;16(4):313–28.

    CAS  Article  PubMed  Google Scholar 

  50. Gray SJ, Trotter CL, Ramsay ME, et al. Epidemiology of meningococcal disease in England and Wales 1993/94 to 2003/04: contribution and experiences of the meningococcal reference unit. J Med Microbiol. 2006;55(Pt 7):887–96.

    Article  PubMed  Google Scholar 

  51. Public Health England. Removal of the infant dose of meningococcal serogroup C (MenC) conjugate vaccine given at three months from 1 July 2016. 2016. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/512311/2016_MenC_infant_schedule_letter-FINAL__1_.pdf. Accessed 13 Oct 2017.

Download references

Acknowledgements

During the peer review process, the manufacturer of MenACWY-TT (Nimenrix®) was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sohita Dhillon.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Sohita Dhillon is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest. David Pace has no conflict of interest to declare.

Additional information about this Adis Drug Review can be found at http://www.medengine.com/Redeem/EF18F06000BFF111.

Additional information

The manuscript was reviewed by: G. Dbaibo, Center for Infectious Diseases Research, American University of Beirut, Beirut, Lebanon; G. Gabutti, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; G. Jönsson Skåne University Hospital, Department of Infectious Diseases, Lund, Sweden.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 121 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dhillon, S., Pace, D. Meningococcal Quadrivalent Tetanus Toxoid Conjugate Vaccine (MenACWY-TT; Nimenrix®): A Review. Drugs 77, 1881–1896 (2017). https://doi.org/10.1007/s40265-017-0828-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-017-0828-8