A randomized study to assess the immunogenicity, antibody persistence and safety of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in children aged 2–10 years

Figures & data

Figure 1. Participants’ progression through the study. ACWY-TT group, group of children who received one dose of MenACWY-TT; Men-PS group, group of children who received one dose of the MenACWY polysaccharide vaccine; ATP, according to protocol; TVC, total vaccinated cohort; N, number of children; *Reasons for non-eligibility: suboptimal responder re-vaccinated with a monovalent meningococcal serogroup C vaccine (n = 41); suboptimal responder who did not come to the booster vaccination visit (n = 2); consent withdrawal (n = 1); and acute leukemia (n = 1)

Table 1. Demographic characteristics of enrolled and vaccinated children (total vaccinated cohort)

Characteristic		ACWY-TT group	Men-PS group
N		231	78
Age (months)	Mean (SD)	71.9 (31.19)	71.6 (30.22)
	Range	24–131	24–125
Gender	Female n (%)	115 (49.8)	37 (47.4)
	Male n (%)	116 (50.2)	41 (52.6)
Race	White - Caucasian / European heritage n (%)	225 (97.4)	76 (97.4)
	African heritage / African American n (%)	1 (0.4)	0 (0.0)
	Asian - East Asian heritage n (%)	1 (0.4)	0 (0.0)
	White - Arabic / North African heritage n (%)	1 (0.4)	0 (0.0)
	Other n (%)	3 (1.3)	2 (2.6)

ACWY-TT group, group of children who received one dose of MenACWY-TT; Men-PS group, group of children who received one dose of the MenACWY polysaccharide vaccine; N, number of children; n, number of children with the specified characteristic; %, percentage (n/N x 100) of children with the specified characteristic; SD, standard deviation.

Table 2. rSBA vaccine response rates at one month after administration of MenACWY-TT or MenACWY polysaccharide vaccine (ATP immunogenicity cohort)

Antibody	ACWY-TT group		Men-PS group		Difference in vaccine response rate (ACWY-TT minus Men-PS)
	N	% [95% CI]	N	% [95% CI]	%	95% CI
						LL	UL
rSBA-MenA	185	98.4* [95.3 – 99.7]	62	91.9 [82.2 – 97.3]	6.44	1.15	16.04
rSBA-MenC	212	94.3* [90.3 – 97.0]	69	81.2 [69.9 – 89.6]	13.18	4.79	24.32
rSBA-MenW-135	199	100* [98.2 – 100]	68	95.6 [87.6 – 99.1]	4.41	1.51	12.21
rSBA-MenY	219	99.1* [96.7 – 99.9]	70	82.9 [72.0 – 90.8]	16.23	8.99	26.78

ACWY-TT group, group of children who received one dose of MenACWY-TT; Men-PS group, group of children who received one dose of the MenACWY polysaccharide vaccine; N, number of children with an rSBA result both pre- and post-vaccination; %, percentage of children with an rSBA vaccine response; 95% CI, 95% confidence interval; LL, lower limit; UL, upper limit; Vaccine response, for initially seronegative children (pre-vaccination rSBA titer < 1:8), post-vaccination rSBA titer ≥ 1:32; for initially seropositive children (pre-vaccination rSBA titer ≥ 1:8), post-vaccination rSBA titer ≥ 4-fold the pre-vaccination rSBA titer; *Indicates higher rSBA vaccine response in the MenACWY-TT group than in the Men-PS group (exploratory analysis).

Table 3. Percentage of children with rSBA titers equal to or above cut-off values, and rSBA GMTs before and one month after vaccination (ATP immunogenicity cohort), one year after vaccination (ATP persistence cohort Year 1), two years after vaccination (ATP persistence cohort Year 2) and three years after vaccination (ATP persistence cohort Year 3). ACWY-TT group, group of children who received one dose of MenACWY-TT; Men-PS group, group of children who received one dose of the MenACWY polysaccharide vaccine; GMT, geometric mean antibody titer calculated on all children; N, number of children with available results; %, percentage of children with titer within the specified range; 95% CI, 95% confidence interval; Pre, pre-vaccination; Month 1, Year 1, Year 2, Year 3, one month, one year, two years and three years after vaccination. *Indicates higher value in the ACWY-TT group compared with the Men-PS group (exploratory analyses). Differences between groups in terms of GMTs are based on values adjusted for pre-vaccination measurements

Antibody	Group	Timing	N	% ≥ 1:8 (95% CI)	% ≥ 1:128 (95% CI)	GMT (95% CI)
rSBA-           MenA	ACWY-TT	Pre	185	67.0 (59.7 – 73.7)	51.9 (44.4 – 59.3)	57.9 (43.3 – 77.5)
		Month 1	225	100 (98.4 – 100)	99.6 (97.5 – 100)	7300.9* (6586.0 – 8093.4)
		Year 1	216	99.5* (97.4 – 100)	99.5* (97.4 – 100)	2448.1* (2149.6 – 2788.1)
		Year 2	208	100* (98.2 – 100)	99.0* (96.6 – 99.9)	1333.4* (1181.9 – 1504.2)
		Year 3	192	100* (98.1 – 100)	99.0* (96.3 – 99.9)	1184.2* (1054.2 – 1330.3)
	Men-PS	Pre	62	64.5 (51.3 – 76.3)	51.6 (38.6 – 64.5)	58.2 (33.8 – 100.1)
		Month 1	75	100 (95.2 – 100)	100 (95.2 – 100)	2033.4 (1667.1 – 2480.2)
		Year 1	71	90.1 (80.7 – 95.9)	80.3 (69.1 – 88.8)	358.5 (230.2 – 558.4)
		Year 2	56	91.1 (80.4 – 97.0)	75.0 (61.6 – 85.6)	202.5 (135.3 – 303.0)
		Year 3	34	91.2 (76.3 – 98.1)	79.4 (62.1 – 91.3)	218.8 (128.9 – 371.5)
rSBA-           MenC	ACWY-TT	Pre	212	62.7 (55.8 – 69.3)	27.8 (21.9 – 34.4)	33.5 (26.0 – 43.1)
		Month 1	225	100 (98.4 – 100)	99.6* (97.5 – 100)	2435.3* (2105.8 – 2816.3)
		Year 1	215	99.5* (97.4 – 100)	89.3* (84.4 – 93.1)	489.5* (419.5 – 571.1)
		Year 2	210	98.6* (95.9 – 99.7)	75.7* (69.3 – 81.4)	256.0* (213.9 – 306.2)
		Year 3	192	98.4* (95.5 – 99.7)	72.9 (66.0 – 79.1)	244.3 (200.8 – 297.3)
	Men-PS	Pre	70	51.4 (39.2 – 63.6)	27.1 (17.2 – 39.1)	24.1 (15.2 – 38.2)
		Month 1	74	100 (95.1 – 100)	94.6 (86.7 – 98.5)	750.2 (555.2 – 1013.7)
		Year 1	65	80.0 (68.2 – 88.9)	58.5 (45.6 – 70.6)	113.5 (67.3 – 191.5)
		Year 2	59	66.1 (52.6 – 77.9)	45.8 (32.7 – 59.2)	59.9 (33.0 – 108.7)
		Year 3	37	83.8 (68.0 – 93.8)	67.6 (50.2 – 82.0)	163.5 (83.8 – 319.2)
rSBA-           MenW-135	ACWY-TT	Pre	199	60.3 (53.1 – 67.2)	45.2 (38.2 – 52.4)	43.1 (32.4 – 57.4)
		Month 1	225	100 (98.4 – 100)	100 (98.4 – 100)	11777.0* (10666.2 – 13003.5)
		Year 1	216	100 (98.3 – 100)	99.1* (96.7 – 99.9)	2983.3* (2628.2 – 3386.3)
		Year 2	210	99.5* (97.4 – 100)	99.0* (96.6 – 99.9)	1298.0* (1135.5 – 1483.7)
		Year 3	196	100* (98.1 – 100)	98.0* (94.9 – 99.4)	1737.1* (1503.8 – 2006.7)
	Men-PS	Pre	68	57.4 (44.8 – 69.3)	35.3 (24.1 – 47.8)	40.1 (23.9 – 67.3)
		Month 1	75	100 (95.2 – 100)	100 (95.2 – 100)	2186.3 (1723.1 – 2773.9)
		Year 1	75	100 (95.2 – 100)	93.3 (85.1 – 97.8)	463.0 (367.4 – 583.5)
		Year 2	54	85.2 (72.9 – 93.4)	68.5 (54.4 – 80.5)	144.0 (90.1 – 230.2)
		Year 3	35	82.9 (66.4 – 93.4)	60.0 (42.1 – 76.1)	112.9 (59.9 – 212.6)
rSBA-           MenY	ACWY-TT	Pre	219	67.1 (60.5 – 73.3)	44.7 (38.0 – 51.6)	57.3 (43.7 – 75.2)
		Month 1	225	100 (98.4 – 100)	99.6 (97.5 – 100)	6641.4* (6044.3 – 7297.4)
		Year 1	216	100* (98.3 – 100)	99.5* (97.4 – 100)	2172.1* (1939.6 – 2432.5)
		Year 2	210	100* (98.3 – 100)	99.5* (97.4 – 100)	1530.2* (1339.2 – 1748.4)
		Year 3	195	100* (98.1 – 100)	100* (98.1 – 100)	1551.6* (1381.2 – 1743.1)
	Men-PS	Pre	70	60.0 (47.6 – 71.5)	40.0 (28.5 – 52.4)	45.5 (26.8 – 77.0)
		Month 1	75	100 (95.2 – 100)	97.3 (90.7 – 99.7)	1409.9 (1085.9 – 1830.5)
		Year 1	71	90.1 (80.7 – 95.9)	78.9 (67.6 – 87.7)	332.4 (213.5 – 517.7)
		Year 2	55	74.5 (61.0 – 85.3)	54.5 (40.6 – 68.0)	96.9 (54.1 – 173.6)
		Year 3	37	81.1 (64.8 – 92.0)	51.4 (34.4 – 68.1)	103.8 (54.3 – 198.3)

Figure 2. Incidence (with 95% CI) of solicited local and general symptoms occurring within 4 d after the first vaccination in children aged 2–5 y (A) or 6–10 y (B) (total vaccinated cohort). ACWY-TT group, group of children who received one dose of MenACWY-TT; Men-PS group, group of children who received one dose of the MenACWY polysaccharide vaccine. Error bars represent 95% confidence intervals