Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT): A review of the evidence and expert opinion

Figures & data

Table 1. Biochemical and structural attributes of the four quadrivalent meningococcal conjugate vaccines.

	MenQuadfi® [15]	Nimenrix® [16]	Menveo® [16]	Menactra® [16]
Manufacturer	Sanofi Pasteur	Pfizer	GSK	Sanofi Pasteur
Type of A, C, Y, W antigen	Polysaccharide	Polysaccharide	Oligosaccharide	Polysaccharide
Type of carrier protein	Tetanus toxoid	Tetanus toxoid	Corynebacterium diphtheriae CRM197 protein	Diphtheria toxin
Linker/spacer
A	ADH	ADH	6-Aminoadipic acid	None
C	None	ADH	6-Aminoadipic acid	None
W	None	None	6-Aminoadipic acid	None
Y	None	None	6-Aminoadipic acid	None
Chemical process
A	Carbodiimide chemistry	Carbodiimide chemistry	Active ester	Reductive amination
C	Reductive amination	Carbodiimide chemistry	Active ester	Reductive amination
W	Reductive amination	Cyanylation	Active ester	Reductive amination
Y	Reductive amination	Cyanylation	Active ester	Reductive amination

Abbreviations: ADH, Adipic acid dihydrazide.

Table 2. Rates of seroprotection and seroresponse in trials with MenACYW-TT and comparators in toddlers aged 12–24 months [14,17–19,26,27].

Study	Seroprotection^a, % (95% CI)		Seroresponse^b, % (95% CI)
MET54 [17] Children aged 12–24 months
	MenACYW-TT (n = 91)	MCV4-TT (n = 86)	MenACYW-TT (n = 91)	MCV4-TT (n = 86)
A	97.8 (92.3–99.7)	91.9 (83.9–96.7)	96.7	91.9
C	100.0 (96.0–100.0)	89.5 (81.1–95.1)	100.0	86.0
Y	98.9 (94.0–100.0)	100 (95.8–100.0)	98.9	98.8
W	98.9 (94.0–100.0)	96.5 (90.1–99.3)	98.9	96.5
MET51 [18] Children aged 12–23 months
	MenACYW-TT (n = 491)	MCV4-TT (n = 395)	MenACYW-TT (n = 491)	MCV4-TT (n = 395)
A (Naïve)	90.8 (86.9–93.8)	89.5 (85.4–92.7)	76.8 (71.5–81.5)	72.5 (67.1–77.6)
A (MCC-primed)	89.8 (84.8–93.7)	98.0 (92.9–99.8)	76.1 (69.6–81.9)	–
A (Naïve and primed)	90.4 (87.4–92.9)	91.6 (88.4–94.2)	76.5 (72.5–80.2)	77.1 (72.6–81.2)
C (Naïve)	99.3 (97.6–99.9)	81.4 (76.4–85.6)	98.3 (96.1–99.4)	71.5 (66.0–76.6)
C (MCC-primed)	99.0 (96.4–99.9)	98.0 (92.9–99.8)	95.4 (91.5–97.9)	–
C (Naïve and primed)	99.2 (97.9–99.8)	85.5 (81.7–88.9)	97.1 (95.2–98.4)	77.4 (72.9–81.4)
Y (Naïve)	93.2 (89.7–95.8)	91.6 (87.8–94.5)	81.9 (77.0–86.1)	79.1 (74.0–83.5)
Y (MCC-primed)	95.9 (92.2–98.2)	91.9 (84.7–96.4)	89.2 (84.0–93.2)	–
Y (Naïve and primed)	94.3 (91.8–96.2)	91.6 (88.5–94.2)	84.8 (81.3–87.9)	78.9 (74.6–82.9)
W (Naïve)	83.6 (78.9–87.7)	83.4 (78.7–87.5)	67.6 (61.9–72.9)	66.6 (60.9–71.9)
W (MCC-primed)	86.7 (81.2–91.1)	85.7 (77.2–92.0)	75.5 (68.9–81.4)	–
W (Naïve and primed)	84.9 (81.4–87.9)	84.0 (80.0–87.5)	70.8 (66.5–74.8)	68.4 (63.6–73.0)
MET57 [19] Children aged 12–23 months
South Korea and Thailand	MenACYW-TT (n = 87)	MenACYW-TT + MMR + V (n = 177)	MenACYW-TT (n = 87)	MenACYW-TT + MMR + V (n = 177)
A	92.0 (84.1–96.7)	97.7 (94.3–99.4)	63.2	78.5
C	100.0 (95.8–100.0)	100.0 (97.9–100.0)	98.9	97.7
Y	95.4 (88.6–98.7)	99.4 (96.9–100.0)	93.2	88.5
W	92.0 (84.1–96.7)	96.0 (92.0–98.4)	83.9	86.4
Mexico	MenACYW-TT (n = 100)	MenACYW-TT + DTaP-IPV-HepB-Hib (n = 200)	MenACYW-TT (n = 100)	MenACYW-TT + DTaP-IPV-HepB-Hib (n = 200)
A	89.9 (81.0–95.5)	92.9 (87.7–96.4)	69.6	67.1
C	100.0 (95.4–100.0)	100.0 (97.6–100.0)	98.7	100.0
Y	98.7 (93.1–100.0)	98.7 (95.4–99.8)	87.3	92.3
W	92.4 (84.2–97.2)	90.3 (84.5–94.5)	82.3	82.6
Russia	MenACYW-TT (n = 100)	MenACYW-TT + PCV13 (n = 200)	MenACYW-TT (n = 100)	MenACYW-TT + PCV13 (n = 200)
A	90.6 (82.9–95.6)	83.7 (77.7–88.6)	71.9 (61.8–80.6)	56.1 (48.9–63.2)
C	99.0 (94.3–100.0)	93.9 (89.5–96.8)	91.7	90.8
Y	97.9 (92.7–99.7)	97.4 (94.1–99.2)	92.7	92.9
W	95.8 (89.7–98.9)	94.4 (90.2–97.2)	82.1	82.1
MEQ00065 [14] Children aged 12–23 months
	MenACYW-TT (n = 227)	MCV4-TT (N = 228)	MenACYW-TT (n = 227)	MCV4-TT (N = 228)
C^c	99.5 (97.4–100)	89.1 (84.1–93.0)	99.5 (97.4–100.0)	83.4 (77.7–88.2)
C^d	100.0 (98.3–100)	–	99.5 (97.4–100.0)	92.9 (88.5–95.9)
		MenC-TT (n = 235)		MenC-TT (n = 235)
C^d	–	100.0 (93.3–100)	–	99.5 (97.4–100.0)

a. Seroprotection was defined as post-vaccination hSBA titers of ≥8 (MET54) or ≥1:8 to each serogroup at Day 30 post-vaccination.

b. Seroresponse was defined in Study MET54 as Day 30 post-vaccination hSBA titers of ≥1:8 to each serogroup in individuals with a baseline titer of <1:8 or a ≥4-fold increase in GMT in individuals with a baseline titer of ≥1:8. In Studies MET51, MET57 and MEQ00065, seroresponse was defined as Day 30 post-vaccination hSBA titers of ≥1:16 to each serogroup in individuals with a baseline titer of <1:8 or a ≥4-fold increase in GMT in individuals with a baseline titer of ≥1:8. Where possible, 95% confidence intervals are reported, but where data were presented graphically in the reported studies, exact 95% confidence interval data were not available.

c. Assessed by serum bactericidal assays with human complement.

d. Assessed by serum bactericidal assays with rabbit complement.

Abbreviations: 95% CI, 95% confidence interval; DTaP-IPV-HepB-Hib, diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b combination vaccine; GMT, geometric mean titer; hSBA, human serum bactericidal antibody assay; MCC, meningococcal C conjugate; MCV4-TT, quadrivalent meningococcal and tetanus conjugate vaccine (Nimenrix®; Pfizer Europe); MenC-TT, monovalent meningococcal C vaccine; MenACYW-TT, quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenQuadfi®, Sanofi); MMR, measles, mumps and rubella vaccine; PCV13, pneumococcal polyvalent vaccine; V, varicella vaccine.

Table 3. Rates of seroprotection and seroresponse in trials with MenACYW-TT and comparators in children aged 2–9 years [23,28].

Study	Seroprotection^a, % (95% CI)		Seroresponse^b, % (95% CI)
MET35 [23] Children aged 2–9 years
	MenACYW-TT (n = 499)	MenACWY-CRM (n = 501)	MenACYW-TT (n = 458)	MenACWY-CRM (n = 460)
A	86.4 (82.9–89.4)	79.3 (75.3–82.9)	55.4 (50.7–60.0)	47.8 (43.2–52.5)
C	97.8 (96.0–98.9)	67.1 (62.6–71.4)	95.2 (92.8–97.0)	47.8 (43.2–52.5)
Y	98.5 (96.9–99.4)	90.8 (87.8–93.3)	91.5 (88.5–93.9)	79.3 (75.3–82.9)
W	94.8 (92.3–96.9)	86.3 (82.8–89.3)	78.8 (74.8–82.5)	64.1 (59.5–68.4)
MET62 [28] Children aged 4–5 years
	MenACYW-TT Primed (n = 40)	MCV4-TT Primed (n = 44)	MenACYW-TT Primed (n = 40)	MCV4-TT Primed (n = 44)
A	100.0 (91.2–100.0)	100.0 (92.0–100.0)	100.0 (91.2–100.0)	95.5 (84.5–99.4)
C	100.0 (91.2–100.0)	100.0 (92.0–100.0)	95.0 (83.1–99.4)	100.0 (92.0–100.0)
Y	97.5 (86.8–99.9)	100.0 (92.0–100.0)	100.0 (91.2–100.0)	100.0 (92.0–100.0)
W	100.0 (91.2–100.0)	100.0 (92.0–100.0)	97.5 (86.8–99.9)	100.0 (92.0–100.0)

a. Seroprotection was defined as post-vaccination hSBA titers of ≥1:8 to each serogroup at Day 30 post-vaccination.

b. Seroresponse in Study MET35 was defined as Day 30 post-vaccination hSBA titers of ≥1:16 to each serogroup in individuals with a baseline titer of <1:8 or a ≥4-fold increase in GMT in individuals with a baseline titer of ≥1:8. Seroresponse in Study MET62 was defined as Day 30 post-vaccination hSBA titers to each serogroup of ≥1:8 in individuals with a baseline titer of <1:8 or a ≥4-fold increase in GMT in individuals with a baseline titer of ≥1:8.

Abbreviations: 95% CI, 95% confidence interval; GMT, geometric mean titer; hSBA, human serum bactericidal antibody assay; MCV4-TT, quadrivalent meningococcal and tetanus conjugate vaccine (Nimenrix®; Pfizer Europe); MenACWY-CRM, quadrivalent meningococcal and diphtheria conjugate vaccine (Menveo®; GlaxoSmithKline); MenACYW-TT, quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenQuadfi®; Sanofi).

Table 4. Rates of seroprotection and seroresponse in trials with MenACYW-TT and comparators in individuals aged 10–55 years [22,24–27].

Study	Seroprotection^a, % (95% CI)		Seroresponse^b, % (95% CI)
MET50 [24] Children aged 10–17 years
	MenACYW-TT (n = 463)	MenACWY-CRM (n = 464)	MenACYW-TT (n = 463)	MenACWY-CRM (n = 464)
A	93.5 (90.9–95.6)	82.8 (79.0–86.1)	75.6 (71.4–79.4)	66.4 (61.9–70.7)
C	98.5 (96.9–99.4)	76.0 (71.9–79.8)	97.2 (95.2–98.5)	72.6 (68.3–76.6)
Y	97.2 (95.2–98.5)	83.2 (79.5–86.5)	97.0 (95.0–98.3)	80.8 (76.9–84.3)
W	99.1 (97.8–99.8)	90.7 (87.7–93.2)	86.2 (82.7–89.2)	66.6 (62.1–70.9)
MET43 [25] Children, adolescents and adults aged 10–55 years
	MenACYW-TT (n = 2508) (3 pooled lots)	MCV4-DT (n = 593)	MenACYW-TT (n = 2508) (3 pooled lots)	MCV4-DT (n = 593)
A	94.7 (93.7–95.5)	88.5 (85.7–91.0)	73.8 (72.0–75.5)	54.6
C	95.7 (94.8–96.4)	76.2 (72.6–79.6)	88.8 (87.5–90.0)	47.9
Y	98.8 (98.3–99.2)	87.9 (84.0–89.6)	91.4 (90.3–92.5)	73.4
W	95.9 (95.3–96.9)	87.0 (85.0–90.4)	80.3 (78.7–81.8)	61.2
MET56 [22] Subjects aged ≥15 years
	MenACYW-TT (n = 394)	MCV4-DT (n = 389)	MenACYW-TT (n = 394)	MCV4-DT (n = 389)
A	100.0 (99.0–100.0)	99.0 (97.4–99.7)	92.2 (89.0–97.7)	87.1 (83.4–90.3)
C	99.5 (98.1–99.9)	99.0 (97.4–99.7)	97.1 (94.9–98.6)	91.8 (88.6–94.3)
Y	99.7 (98.6–100.0)	99.5 (98.6–100.0)	97.4 (95.3–98.7)	95.6 (93.1–97.4)
W	100.0 (99.0–100.0)	99.7 (98.2–99.9)	98.2 (96.3–99.3)	90.7 (87.4–93.4)

a. Seroprotection was defined as post-vaccination hSBA titers ≥1:8 to each serogroup at Day 30 post-vaccination.

b. Seroresponse was defined in Study MET50 as Day 30 post-vaccination hSBA titers of ≥1:8 to each serogroup in individuals with a baseline titer of <1:8 or a ≥4-fold increase in GMT in individuals with a baseline titer of ≥1:8. In studies MET43 and MET56, it was defined as Day 30 post-vaccination hSBA titers of ≥1:16 to each serogroup in individuals with a baseline titer of <1:8 or a ≥4-fold increase in GMT in individuals with a baseline titer of ≥1:8. Where possible, 95% confidence intervals are reported, but where data were presented graphically in the reported studies, exact 95% confidence interval data were not available.

Abbreviations: 95% CI, 95% confidence interval; GMT, geometric mean titer; hSBA, human serum bactericidal antibody assay; MenACWY-CRM, quadrivalent meningococcal and diphtheria conjugate vaccine (Menveo®; GlaxoSmithKline); MenACYW-TT, quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenQuadfi®; Sanofi); MCV4-DT, quadrivalent meningococcal and diphtheria conjugate vaccine (Menactra®; Sanofi).

Table 5. Rates of seroprotection and seroresponse in trials with MenACYW-TT and comparators in individuals aged ≥ 56 years [20,21,26,27].

Study	Seroprotection^a, % (95% CI)		Seroresponse^b, % (95% CI)
MET44 [20] Adults aged ≥56 years
	MenACYW-TT (n = 195)	MPSV4 (n = 94)	MenACYW-TT (n = 195)	MPSV4 (n = 94)
A	93.8 (89.5–96.8)	85.1 (76.3–91.6)	65.1	46.8
C	74.9 (68.2–80.8)	62.8 (52.2–72.5)	70.8	59.6
Y	80.5 (74.2–85.8)	59.6 (49.0–69.6)	75.4	48.9
W	79.5 (73.1–84.9)	60.6 (50.0–70.6)	74.4	55.3
MET49 [21] Adults aged ≥56 years
	MenACYW-TT (n = 433)	MPSV4 (n = 431)	MenACYW-TT (n = 433)	MPSV4 (n = 431)
A	89.4 (86.1–92.1)	84.2 (80.4–87.5)	58.2 (53.4–62.9)	42.5 (37.7–47.3)
C	90.1 (86.9–92.7)	71.0 (66.5–75.2)	77.1 (72.9–81.0)	49.7 (44.8–54.5)
Y	91.7 (88.7–94.1)	67.7 (63.1–72.1)	74.4 (70.0–78.4)	44.8 (40.0–49.6)
W	77.4 (73.1–81.2)	63.1 (58.4–67.7)	62.6 (57.8–67.2)	44.8 (40.0–49.6)

a. Seroprotection was defined as post-vaccination hSBA titers ≥1:8 to each serogroup at Day 30 post-vaccination.

b. Seroresponse was defined in Study MET44 as Day 30 post-vaccination hSBA titers of ≥1:8 to each serogroup in individuals with a baseline titer of <1:8 or a ≥4-fold increase in GMT in individuals with a baseline titer of ≥1:8. In Study MET49, seroresponse was defined as Day 30 post-vaccination hSBA titers of ≥1:16 to each serogroup in individuals with a baseline titer of <1:8 or a ≥4-fold increase in GMT in individuals with a baseline titer of ≥1:8. Where possible, 95% confidence intervals are reported, but where data were presented graphically in the reported studies, exact 95% confidence interval data were not available.

Abbreviations: 95% CI, 95% confidence interval; GMT, geometric mean titer; hSBA, human serum bactericidal antibody assay; MenACYW-TT, quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenQuadfi®; Sanofi); MPSV4, quadrivalent meningococcal polysaccharide vaccine (Menomune®; Sanofi).

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Data availability statement

Data sharing is not applicable to this article, as no new data were created or analyzed in this study.