Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study
M S Dhingra, L Namazova-Baranova, J L Arredondo-Garcia, K-H Kim, K Limkittikul, W Jantarabenjakul, O Perminova, I A R Kobashi, C-W Bae, J Ojeda, J Park, D Chansinghakul, S B'Chir, D Neveu, M Bonaparte, E Jordanov, M S Dhingra, L Namazova-Baranova, J L Arredondo-Garcia, K-H Kim, K Limkittikul, W Jantarabenjakul, O Perminova, I A R Kobashi, C-W Bae, J Ojeda, J Park, D Chansinghakul, S B'Chir, D Neveu, M Bonaparte, E Jordanov
Abstract
Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.
Keywords: Coadministration; MenACYW-TT; paediatric vaccines; toddlers.
Conflict of interest statement
MSD, EJ, JO, JP, DC, DN, SB'C and MB are employees of Sanofi Pasteur, and may hold shares and/or stock options in the company. JLA-G received Sanofi-Pasteur resources to carry out this project through his institution. LN-B, K-HK, KL, C-WB, IARK OP and WJ declare no conflict of interest.
Figures
References
- Borrow R, et al. (2017) The global meningococcal initiative: global epidemiology, the impact of vaccines on meningococcal disease and the importance of herd protection. Expert Review of Vaccines 16, 313–328.
- Olbrich KJ et al. (2018) Systematic review of invasive meningococcal disease: sequelae and quality of life impact on patients and their caregivers. Infectious Diseases and Therapy 7, 421–438.
- Acevedo R et al. (2019) The global meningococcal initiative meeting on prevention of meningococcal disease worldwide: epidemiology, surveillance, hypervirulent strains, antibiotic resistance and high-risk populations. Expert Review of Vaccines 18, 15–30.
- Pace D and Pollard AJ (2012) Meningococcal disease: clinical presentation and sequelae. Vaccine 30, B3–B9.
- Centers for Disease Control and Prevention. (2017) Enhanced Meningococcal Disease Surveillance Report. Available at .
- European Centre for Disease Prevention and Control. Invasive meningococcal disease: Annual Epidemiological Report for 2017. Available at .
- Vespa Presa J et al. (2019) Epidemiological burden of meningococcal disease in Latin America: a systematic literature review. International Journal of Infectious Diseases 85, 37–48.
- European Centre for Disease Prevention and Control. Factsheet about meningococcal disease. Available at .
- Tsang RS et al. (2019) Increase in ST-11 serogroup W Neisseria meningitidis invasive meningococcal disease in Canada, 2016–2018. Canada Communicable Disease Report = Releve des Maladies Transmissibles au Canada 45, 164–169.
- Booy R et al. (2019) Recent changes in the epidemiology of Neisseria meningitidis serogroup W across the world, current vaccination policy choices and possible future strategies. Human Vaccines & Immunotherapeutics 15, 470–480.
- Krone M et al. (2019) Increase of invasive meningococcal serogroup W disease in Europe, 2013 to 2017. Eurosurveillance 24, 1800245.
- Bröker M et al. (2015) Meningococcal serogroup Y disease in Europe: continuation of high importance in some European regions in 2013. Human Vaccines & Immunotherapeutics 11, 2281–2286.
- Martin NV et al. (2016) Rise in invasive serogroup W meningococcal disease in Australia 2013–2015. Communicable Diseases Intelligence Quarterly Report 40, E454–e459.
- Presa J et al. (2019) Epidemiologic trends, global shifts in meningococcal vaccination guidelines, and data supporting the use of MenACWY-TT vaccine: a review. Infectious Diseases and Therapy 8, 307–333.
- Findlow H and Borrow R (2016) Interactions of conjugate vaccines and co-administered vaccines. Human Vaccines & Immunotherapeutics 12, 226–230.
- Bröker M et al. (2017) Polysaccharide conjugate vaccine protein carriers as a “neglected valency” – potential and limitations. Vaccine 35, 3286–3294.
- Anez G et al. (2020) Immunogenicity and safety of a booster dose of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adolescents and adults: a phase III randomized study. Human Vaccines & Immunotherapeutics 16, 1292–1298.
- Vesikari T et al. (2020) Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in healthy toddlers: a phase II randomized study. Human Vaccines & Immunotherapeutics 16, 1306–1312.
- Kirstein J et al. (2020) Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adults 56 years of age and older: a phase II randomized study. Human Vaccines & Immunotherapeutics 16, 1299–1305.
- Esteves-Jaramillo A et al. (2020) Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in ≥56-year-olds: a phase III randomized study. Vaccine 38, 4405–4411.
- Dhingra MS et al. (2020) Immunogenicity, safety and inter-lot consistency of a meningococcal conjugate vaccine (MenACYW-TT) in adolescents and adults: a phase III randomized study. Vaccine 38, 5194–5201.
- Baccarini CI et al. (2020) Safety and immunogenicity of a quadrivalent meningococcal conjugate vaccine in healthy meningococcal-naïve children 2-9 years of age: a phase III, randomized study. The Pediatric Infectious Disease Journal 39, 955–960.
- van der Vliet D et al. (2021) Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) versus a licensed quadrivalent meningococcal conjugate vaccine in meningococcal vaccine-naïve and meningococcal C conjugate vaccine-primed toddlers: a phase III randomized study. Epidemiology and Infection 149, e50.
- Chang LJ et al. (2020) A phase II, randomized, immunogenicity and safety study of a quadrivalent meningococcal conjugate vaccine, MenACYW-TT, in healthy adolescents in the United States. Vaccine 38, 3560–3569.
- World Health Organization, WHO vaccine-preventable diseases: monitoring system. 2020 global summary. Available at . Accessed 15 October 2020.
- Maslanka SE et al. (1997) Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. The multilaboratory study group. Clinical and Diagnostic Laboratory Immunology 4, 156–167.
- Pina LM et al. (2012) Safety and immunogenicity of a quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine in infants and toddlers: three multicenter phase III studies. The Pediatric Infectious Disease Journal 31, 1173–1183.
- Tregnaghi MW, Zambrano B and Santos-Lima E (2011) Immunogenicity and safety of an investigational hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae B conjugate combined vaccine in healthy 2-, 4–, and 6-month-old argentinean infants. The Pediatric Infectious Disease Journal 30, e88–e96.
- Shehab ZM, Brunell PA and Cobb E (1984) Epidemiological standardization of a test for susceptibility to mumps. Journal of Infectious Diseases 149, 810–812.
- Johnson CE et al. (1996) Antibody persistence after primary measles-mumps-rubella vaccine and response to a second dose given at four to six vs. Eleven to thirteen years. The Pediatric Infectious Disease Journal 15, 687–692.
- Keller PM et al. (1986) Purification of individual varicella-zoster virus (VZV) glycoproteins gpI, gpII, and gpIII and their use in ELISA for detection of VZV glycoprotein-specific antibodies. Journal of Virological Methods 14, 177–188.
- Wasmuth EH and Miller WJ (1990) Sensitive enzyme-linked immunosorbent assay for antibody to varicella-zoster virus using purified VZV glycoprotein antigen. Journal of Medical Virology 32, 189–193.
- Provost PJ et al. (1991) Antibody assays suitable for assessing immune responses to live varicella vaccine. Vaccine 9, 111–116.
- Keshavan P et al. (2018) An update of clinical experience with the quadrivalent meningococcal ACWY-CRM conjugate vaccine. Expert Review of Vaccines 17, 865–880.
- Gasparini R et al. (2016) Safety and immunogenicity of a quadrivalent meningococcal conjugate vaccine and commonly administered vaccines after coadministration. The Pediatric Infectious Disease Journal 35, 81–93.
- Assaf-Casals A and Dbaibo G (2016) Meningococcal quadrivalent tetanus toxoid conjugate vaccine (MenACWY-TT, Nimenrix™): a review of its immunogenicity, safety, co-administration, and antibody persistence. Human Vaccines & Immunotherapeutics 12, 1825–1837.
- Javadekar B et al. (2018) Safety and immunogenicity of two doses of a quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine in Indian and Russian children aged 9 to 17 months. Indian Pediatrics 55, 1050–1055.
- Cutland CL et al. (2018) Immunogenicity and safety of one or two doses of the quadrivalent meningococcal vaccine MenACWY-TT given alone or with the 13-valent pneumococcal conjugate vaccine in toddlers: a phase III, open-label, randomised study. Vaccine 36, 1908–1916.
- Lawrence GL et al. (2016) Meningococcal disease epidemiology in Australia 10 years after implementation of a national conjugate meningococcal C immunization programme. Epidemiology and Infection 144, 2382–2391.
- Trotter CL et al. (2004) Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction. Lancet 364, 365–367.
- Jafri RZ, et al. (2013) Global epidemiology of invasive meningococcal disease. Population Health Metrics 11, 17.
Source: PubMed