Review of clinical studies comparing meningococcal serogroup C immune responses induced by MenACWY-TT and monovalent serogroup C vaccines

Figures & data

Table 1. Meningococcal conjugate and recombinant protein vaccines used globally

Vaccine	Type	Meningococcal serogroups (other antigens)	European indication, age*
Monovalent
MenAfricVac (PsA-TT)^Citation6,Citation7	TT conjugate	A	Not licensed in Europe
Menjugate (MenC-CRM197 adsorbed to aluminum hydroxide)^Citation8	CRM197 conjugate	C	≥2 mo
Meningitec (MenC-CRM197 adsorbed to aluminum phosphate)^Citation9,Citation10	CRM197 conjugate	C	Discontinued in Europe
NeisVac-C (MenC-TT)^Citation11	TT conjugate	C	≥2 mo
Bexsero (MenB-4C)^Citation12	Recombinant protein	B	≥2 mo
Trumenba (MenB-FHbp)^Citation13	Recombinant protein	B	≥10 y
Combination
MenHibrix (HibMenCY-TT)^Citation14	TT conjugate	C, Y (Hib)	Not licensed in Europe
Menitorix (Hib-MenC-TT)^Citation15	TT conjugate	C (Hib)	≥2 mo
Quadrivalent
Nimenrix (MenACWY-TT)^Citation16	TT conjugate	A, C, W, Y	≥6 wk
Menveo (MenACWY-CRM197)^Citation17	CRM197 conjugate	A, C, W, Y	≥2 y
Menactra (MenACWY-D)^Citation18	D conjugate	A, C, W, Y	Not licensed in Europe
MenQuadfi (MenACYW-TT)^Citation19	TT conjugate	A, C, W, Y	Not licensed in Europe

CRM₁₉₇, diphtheria protein cross-reactive material 197; D, diphtheria toxin; Hib, Haemophilus influenzae type b; TT, tetanus toxoid.

*For currently available vaccines.

Figure 1. Countries with recent MenACWY vaccine recommendations.^31,37–59

*In all provinces apart from Quebec. ^†Malta is not shown to scale or to shape.

Table 2. Overview of included studies

Study	Clinical trial registration number	Location	Study design	Total subjects, n	Vaccine comparison relevant to this review	Subjects of comparison, n
Merino Arribas 2017^Citation60	ClinicalTrials.gov NCT01144663	Estonia, Germany, Spain	Phase 3, open, randomized, controlled	2095	MenACWY-TT MenC-TT MenC-CRM197/Al(OH)3	Healthy infants aged 6–12 wk at first vaccination, n = 1567
Vesikari 2011^Citation61	ClinicalTrials.gov NCT00474266	Finland	Phase 3, open, randomized, controlled	1000	MenACWY-TT MenC-CRM197/AlPO4	Healthy toddlers aged 12–23 mo, n = 499
Vesikari 2012^Citation67	ClinicalTrials.gov NCT00427908	Finland	Phase 2, open, randomized, controlled	304	MenACWY-TT MenC-CRM197/AlPO4	Healthy toddlers aged 12–23 mo, n = 304
Knuf 2010^6Citation3	ClinicalTrials.gov NCT00126984	Germany, Austria	Phase 2, blind, randomized, controlled	508	MenACWY-TT MenC-CRM197/AlPO4	Healthy toddlers aged 12–14 mo, n = 96
Knuf 2011^Citation63	ClinicalTrials.gov NCT00508261	Austria, Germany, Greece	Phase 3, open, randomized, controlled	793	MenACWY-TT MenC-CRM197/AlPO4	Healthy toddlers aged 12–23 mo, n = 347
Knuf 2013^Citation64	ClinicalTrials.gov NCT00674583	Germany, France	Phase 3, open, randomized, controlled	414	MenACWY-TT MenC-CRM197/Al(OH)3	Healthy children aged 2–10 y, n = 414
Vesikari 2015^Citation65	ClinicalTrials.gov NCT00955682 (extension study to NCT00474266)	Finland	Phase 3, open, controlled, persistence/booster extension	293	MenACWY-TT MenC-CRM197/AlPO4	Healthy children aged 60–69 mo who had previously received MenACWY-TT or MenC-CRM197/AlPO4 as toddlers, n = 293
Van Ravenhorst 2017^Citation66	Clinicaltrialsregister.eu EudraCT 2013–001823-38 Trialregister.nl NTR4430	The Netherlands	Phase 4, open, randomized, controlled	501	MenACWY-TT MenC-TT	Healthy adolescents aged 10, 12, and 15 y previously vaccinated with MenC-TT at 14 mo–3 y; n = 501

MenACWY-TT, meningococcal serogroups A, C, W, and Y vaccine conjugated to tetanus toxoid as a carrier protein; MenC-CRM₁₉₇/Al(OH)₃, meningococcal serogroup C vaccine conjugated to the nontoxic form of diphtheria protein cross-reactive material 197 and adsorbed onto aluminum hydroxide; MenC-CRM₁₉₇/AlPO₄, meningococcal serogroup C vaccine conjugated to the nontoxic form of diphtheria protein cross-reactive material 197 and adsorbed onto aluminum phosphate; MenC-TT, meningococcal serogroup C vaccine conjugated to tetanus toxoid.

Figure 2. Serum bactericidal antibody measurements against serogroup C at 1 month postprimary and postbooster vaccination in infants vaccinated with MenACWY-TT, MenC-TT, or MenC-CRM₁₉₇/Al(OH)₃ at 2, 4, and 12 months of age.⁶⁰ (a) Percentage of infants with rSBA titers ≥1:8, (b) rSBA GMTs, (c) percentage of infants with hSBA titers ≥1:8, and (d) hSBA GMTs.

Subjects had blood samples collected at 1 month (range, 21–48 days) after the second primary dose (primary ATP cohort) and the booster dose (booster ATP cohort). Panel A. Postprimary, n = 455–457; postbooster, n = 446–463. Panel B. Postprimary, n = 455–457; postbooster, n = 446–463. Panel C. Postprimary, n = 202–226; postbooster, n = 216–221. Panel D. Postprimary, n = 202–226; postbooster, n = 216–221. ATP = according to protocol; GMT = geometric mean titer; hSBA = serum bactericidal antibody using human complement; MenACWY-TT = meningococcal serogroups A, C, W, and Y vaccine conjugated to tetanus toxoid as a carrier protein; MenC-CRM₁₉₇/Al(OH)₃ = meningococcal serogroup C vaccine conjugated to the nontoxic form of diphtheria protein cross-reactive material 197 and adsorbed onto aluminum hydroxide; MenC-TT = meningococcal serogroup C vaccine conjugated to tetanus toxoid; rSBA = serum bactericidal antibody using baby rabbit complement.

Figure 3. Serum bactericidal antibody measurements against serogroup C at 1 month/42 days postvaccination in toddlers administered a single dose of MenACWY-TT or MenC-CRM₁₉₇/AlPO₄ vaccine.^61–63,67 (a) Percentage of toddlers with rSBA titers ≥1:8, (b) rSBA GMTs, (c) percentage of toddlers with hSBA titers ≥1:8, and (d) hSBA GMTs.

Subjects had blood samples collected at 1 month (range, 21–48 days) after the second primary dose (primary ATP cohort) and the booster dose (booster ATP cohort). Panel A. Postprimary, n = 455–457; postbooster, n = 446–463. Panel B. Postprimary, n = 455–457; postbooster, n = 446–463. Panel C. Postprimary, n = 202–226; postbooster, n = 216–221. Panel D. Postprimary, n = 202–226; postbooster, n = 216–221. ATP = according to protocol; GMT = geometric mean titer; hSBA = serum bactericidal antibody using human complement; MenACWY-TT = meningococcal serogroups A, C, W, and Y vaccine conjugated to tetanus toxoid as a carrier protein; MenC-CRM₁₉₇/Al(OH)₃ = meningococcal serogroup C vaccine conjugated to the nontoxic form of diphtheria protein cross-reactive material 197 and adsorbed onto aluminum hydroxide; MenC-TT = meningococcal serogroup C vaccine conjugated to tetanus toxoid; rSBA = serum bactericidal antibody using baby rabbit complement.

Figure 4. Serum bactericidal antibody measurements against serogroup C at 1 month postvaccination in individuals aged ≥2 years administered a single or booster dose of MenACWY-TT, MenC-CRM₁₉₇/Al(OH)_3, MenC-TT, or MenC-CRM₁₉₇/AlPO₄ vaccine.^64–66 (a) Percentage of individuals with rSBA titers ≥1:8, (b) rSBA GMTs, (c) percentage of individuals with hSBA titers ≥1:8, and (d) hSBA GMTs.

*MenC-CRM₁₉₇ vaccine = MenC-CRM₁₉₇/Al(OH)₃ in Knuf 2013⁶⁴ and MenC-CRM₁₉₇/AlPO₄ in Vesikari 2015.⁶⁵ All analyses were performed on ATP immunogenicity cohorts. Knuf 2013: Subjects aged 2–10 years administered a single vaccine dose; MenACWY-TT, n = 293; MenC-CRM₁₉₇/Al(OH)₃, n = 97; blood samples collected at 1 month postvaccination (range, 21–48 days).⁶⁴ Vesikari 2015: Subjects aged 5 years (60–69 months) who had previously received 1 dose of MenACWY-TT or MenC-CRM₁₉₇/AlPO₄ as toddlers were administered a booster dose of the same vaccine. MenACWY-TT, n = 209–215; MenC-CRM₁₉₇/AlPO₄, n = 33–43; blood samples collected at 1 month postbooster (range, 21–48 days).⁶⁵ van Ravenhorst 2017: Subjects aged 10, 12, or 15 years who had previously received a primary dose of MenC-TT as toddlers were administered a booster vaccine dose; MenACWY-TT, n = 78–79; MenC-TT, n = 78–89; blood samples collected at 1 month postbooster (ATP blood sampling window not available).⁶⁶ ATP = according to protocol; GMT = geometric mean titer; hSBA = serum bactericidal antibody using human complement; MenACWY-TT = meningococcal serogroups A, C, W, and Y vaccine conjugated to tetanus toxoid as a carrier protein; MenC-CRM₁₉₇/Al(OH)₃ = meningococcal serogroup C vaccine conjugated to the nontoxic form of diphtheria protein cross-reactive material 197 and adsorbed onto aluminum hydroxide; MenC-CRM₁₉₇/AlPO₄ = meningococcal serogroup C vaccine conjugated to the nontoxic form of diphtheria protein cross-reactive material 197 and adsorbed onto aluminum phosphate; MenC-TT = meningococcal serogroup C vaccine conjugated to tetanus toxoid; rSBA = serum bactericidal antibody using baby rabbit complement.

World Health Organization. Immunization standards: meningococcal A conjugate 10 dose presentation. World Health Organization. [ accessed 2020 May 28] https://www.who.int/immunization_standards/vaccine_quality/PQ_197_MenAconjugate_10dose_SII/en/

 Google Scholar

MenAfriVac (meningococcal A conjugate vaccine). Full Prescribing Information. Pune (India): Serum Institute of India; 2015.

 Google Scholar

Menjugate 10 micrograms suspension for injection (Meningococcal group C conjugate vaccine). Summary of Product Characteristics, Siena (Italy): GSK Vaccines S.r.l.; 2018.

 Google Scholar

Meningitec (meningococcal serogroup C conjugate vaccine). Full Prescribing Information. West Ryde (NSW, Australia): Pfizer Australia Pty Ltd; 2011.

 Google Scholar

Serogroup C meningococcal conjugate vaccines: new preparations. Effective from age two months. Prescrire Int. 2003;12(64):43–46.

 PubMedGoogle Scholar

NeisVac-C (Meningococcal Group C Polysaccharide Conjugate Vaccine Adsorbed). Summary of Product Characteristics. Sandwich (Kent, UK): Pfizer Limited; 2019.

 Google Scholar

Bexsero (Meningococcal group B Vaccine [rDNA, component, adsorbed]). Summary of Product Characteristics. Uxbridge (Middlesex, UK): GlaxoSmithKline UK; 2019.

 Google Scholar

Trumenba (MenB-FHbp). Summary of Product Characteristics. Sandwich (Kent, UK): Pfizer Ltd; 2018.

 Google Scholar

MENHIBRIX (Hib-MenCY-TT). Full Prescribing Information. Rixensart (Belgium): GlaxoSmithKline; 2013.

 Google Scholar

Breton MC, Huang L, Snedecor SJ, Cornelio N, Fanton-Aita F. Cost-effectiveness of alternative strategies for vaccination of adolescents against serogroup B IMD with the MenB-FHbp vaccine in Canada. Can J Public Health. 2020;111(2):182–92. doi:10.17269/s41997-019-00275-4.

 PubMed Web of Science ®Google Scholar

NIMENRIX. Summary of Product Characteristics. Sandwich (Kent, UK): Pfizer Limited; 2020.

 Google Scholar

Menveo (Meningococcal Group A, C, W135 and Y conjugate vaccine). Summary of Product Characteristics. Sovicille (Italy): GSK vaccines S.r.l.; 2014.

 Google Scholar

Meites E, Szilagyi PG, Chesson HW, Unger ER, Romero JR, Markowitz LE. Human papillomavirus vaccination for adults: updated recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2019;68(32):698–702. doi:10.15585/mmwr.mm6832a3.

 PubMed Web of Science ®Google Scholar

MenQuadfi (MenACWY-TT). Full Prescribing Information. Swiftwater (PA): Sanofi Pasteur Inc; 2020.

 Google Scholar

Booy R, Gentile A, Nissen M, Whelan J, Abitbol V. Recent changes in the epidemiology of Neisseria meningitidis serogroup W across the world, current vaccination policy choices and possible future strategies. Hum Vaccin Immunother. 2019;15(2):470–80. doi:10.1080/21645515.2018.1532248.

 PubMed Web of Science ®Google Scholar

Fazio C, Neri A, Renna G, Vacca P, Antonetti R, Barbui AM, Daprai L, Lanzafame P, Rossi L, Santino I, et al. Persistent occurrence of serogroup Y/sequence type (ST)-23 complex invasive meningococcal disease among patients aged five to 14 years, Italy, 2007 to 2013. Eurosurveillance. 2015;20(45):30061. https://doi.org/10.2807/1560-7917.ES.2015.20.45.30061.

 Web of Science ®Google Scholar

Government of Malta. National immunisation schedule (Immunisation schedule for ages 0-16 years). [ accessed 2020 July 21] https://deputyprimeminister.gov.mt/en/phc/pchyhi/Pages/National-Immunisation-Schedule.aspx.

 Google Scholar

Programa Nacional de Imunizações. Informe Técnico. Orientações técnico-operacionais para a Vacinação dos Adolescentes com a Vacina Meningocócica ACWY (conjugada). 2020.

 Google Scholar

Vesikari T, Forsten A, Bianco V, Van der Wielen M, Miller JM. 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. doi:10.1097/INF.0000000000000897.

 PubMed Web of Science ®Google Scholar

Stinson C, Burman C, Presa J, Abalos M. Atypical presentation of invasive meningococcal disease caused by serogroup W meningococci. Epidemiol Infect. 2020;148:e12. doi:10.1017/S0950268819002152.

 PubMed Web of Science ®Google Scholar

Vesikari T, Karvonen A, Bianco V, Van der Wielen M, Miller J. 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. doi:10.1016/j.vaccine.2011.03.043.

 PubMed Web of Science ®Google Scholar

Knuf M, Kieninger-Baum D, Habermehl P, Muttonen P, Maurer H, Vink P, Poolman J, Boutriau D. A dose-range study assessing immunogenicity and safety of one dose of a new candidate meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine administered in the second year of life and in young children. Vaccine. 2010;28(3):744–53. doi:10.1016/j.vaccine.2009.10.064.

 PubMed Web of Science ®Google Scholar

Knuf M, Pantazi-Chatzikonstantinou A, Pfletschinger U, Tichmann-Schumann I, Maurer H, Maurer L, Fischbach T, Zinke H, Pankow-Culot H, Papaevangelou V, 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. doi:10.1016/j.vaccine.2011.03.009.

 PubMed Web of Science ®Google Scholar

Knuf M, Romain O, Kindler K, Walther U, Tran PM, Pankow-Culot H, Fischbach T, Kieninger-Baum D, Bianco V, Baine Y, 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. doi:10.1007/s00431-012-1924-0.

 PubMed Web of Science ®Google Scholar