Immunogenicity and safety of the first indigenously developed Indian tetravalent influenza vaccine (split virion) in healthy children (6 months to 17 years of age): a randomized, multicenter, phase III clinical trial

Figures & data

Table 1. Demographic and baseline characteristics of all enrolled subjects

	TetIV Group	TriIV Group
Total Study Population
	N = 151	N = 155
Age (Years)	6.0 ± 4.2	6.3 ± 4.6
Sex* Male	81 (53.6%)	89 (57.4%)
Female	70 (46.4%)	66 (42.6%)
Height (cm)	110.6 ± 29.8	110.5 ± 29.8
Weight (kg)	21.6 ± 14.4	21.7 ± 14.0
Cohort 1 (9 to 17 years)
	N = 51	N = 52
Age (Years)	11.3 ± 1.9	12.0 ± 2.4
Sex* Male	32 (62.8%)	35 (67.3%)
Female	19 (37.3%)	17 (32.7%)
Height (cm)	144.9 ± 12.2	145.2 ± 12.9
Weight (kg)	38.7 ± 12.0	37.0 ± 13.5
Cohort 2 (3 to 8 years)
	N = 49	N = 51
Age (Years)	4.8 ± 1.2	5.1 ± 1.5
Sex* Male	27 (55.1%)	27 (52.9%)
Female	22 (44.9%)	24 (47.1%)
Height (cm)	106.8 ± 16.5	106.5 ± 12.9
Weight (kg)	15.7 ± 3.1	17.2 ± 4.5
Cohort 3 (6 to 35 months)
	N = 51	N = 52
Age (Months)	21.1 ± 8.7	20.1 ± 8.6
Sex* Male	22 (43.1%)	27 (51.9%)
Female	29 (56.9%)	25 (48.1%)
Height (cm)	80.0 ± 9.1	79.7 ± 11.6
Weight (kg)	10.3 ± 2.3	10.6 ± 2.6

Data expressed as mean ± SD

*Data expressed as n (%)

Figure 1. Flow of subjects in the study

Table 2. Seroconversion and seroprotection rates, and GMTs in the two groups, 28 days after the last vaccination

Immunogenicity end point	TetIV Group (N = 148)	TriIV Group (N = 150)	TetIV – TriIV or TetIV/TriIV^^
A/Michigan (A/H1N1)
Seroconversion*	140 (94.6%) (89.6% – 97.6%)	141 (94.0%) (88.9% – 97.2%)	0.6% (−4.7% – 5.9%)
Seroprotection*	148 (100.0%) (97.5% – 100.0%)	150 (100.0%) (97.6% – 100.0%)	0.0% (0.0% – 0.0%)
GMT^#	935.3 (797.9–1096.3)	1030.1 (902.0–1176.5)	0.91 (0.73–1.12)
A/Hong Kong (A/H3N2)
Seroconversion*	139 (93.9%) (88.8% – 97.2%)	141 (94.0%) (88.9% – 97.2%)	−0.1% (−5.3% – 5.5%)
Seroprotection*	147 (99.3%) (96.3% – 100.0%)	150 (100.0%) (97.6% – 100.0%)	−0.7% (−2.0% – 0.6%)
GMT^#	1543.7 (1264.1–1885.3)	1689.0 (1437.4–1984.6)	0.91 (0.71–1.18)
B/Brisbane (B/Victoria)
Seroconversion*	135 (91.2%) (85.4% – 95.2%)	125 (83.3%) (76.4% – 88.9%)	7.9% (0.3% – 15.5%)
Seroprotection*	138 (93.2%) (87.9% – 96.7%)	127 (84.7%) (77.9% – 90.0%)	8.5% (1.5% – 15.7%)
GMT^#	203.2 (162.5–254.1)	201.6 (156.7–259.3)	1.01 (0.72–1.41)
B/Phuket (B/Yamagata)
Seroconversion*	129 (87.2%) (80.7% – 92.1%)	51 (34.0%) (26.5% – 42.2%)	53.2% (42.1% – 64.3%)
Seroprotection*	131 (88.5%) (82.2% – 93.2%)	58 (38.7%) (30.8% – 47.0%)	49.8% (38.9% – 60.8%)
GMT^#	91.2 (76.0–109.5)	22.6 (18.4–27.7%)	4.04 (3.08–5.31)

*Data presented as n (%) (95% CI)

^#Data presented as geometric mean (95% CI)

^TetIV – TriIV values given for seroconversion and seroprotection rates; TetIV/TriIV ratio given for GMT 28 days after the last dose

Table 3. Seroconversion rate 28 days after the last vaccination in the three cohorts

	TetIV Group	TriIV Group	P value
A/Michigan (A/H1N1)
Cohort 1	45/50 (90.0%) (78.2% – 96.7%)	48/52 (92.3%) (81.5% – 97.9%)	0.95
Cohort 2	45/48 (93.8%) (82.8% – 98.7%)	45/49 (91.8%) (80.4% – 97.7%)	0.98
Cohort 3	50/50 (100.0%) (92.9% – 100.0%)	48/49 (98.0%) (89.1% – 99.9%)	0.99
A/Hong Kong (A/H3N2)
Cohort 1	47/50 (94.0%) (83.5% – 98.7%)	45/52 (86.5%) (74.2% – 94.4%)	0.35
Cohort 2	43/48 (89.6%) (77.3% – 96.5%)	47/49 (95.9%) (86.0% – 99.5%)	0.42
Cohort 3	49/50 (98.0%) (89.4% – 99.9%)	49/49 (100.0%) (92.7% – 100.0%)	0.99
B/Brisbane (B/Victoria)
Cohort 1	44/50 (88.0%) (75.7% – 95.5%)	46/52 (88.5%) (76.6% – 95.6%)	0.81
Cohort 2	43/48 (89.6%) (77.3% – 96.5%)	43/49 (87.8%) (75.2% – 95.4%)	0.97
Cohort 3	48/50 (96.0%) (86.3% – 99.5%)	36/49 (73.5%) (58.9% – 85.1%)	0.004
B/Phuket (B/Yamagata)
Cohort 1	44/50 (88.0%) (75.7% – 95.5%)	20/52 (38.5%) (25.3% – 53.0%)	<0.01
Cohort 2	40/48 (83.3%) (69.8% – 92.5%)	22/49 (44.9%) (30.7% – 59.8%)	0.0002
Cohort 3	45/50 (90.0%) (78.2% – 96.7%)	9/49 (18.4%) (8.8% – 32.0%)	<0.0001

Data presented as n/N (%) (95% CI)

P value based on chi-square test

Table 4. Seroprotection rate 28 days after the last vaccination in the three cohorts

	TetIV Group	TriIV Group	P value
A/Michigan (A/H1N1)
Cohort 1	50/50 (100.0%) (92.9% – 100.0%)	52/52 (100.0%) (93.2% – 100.0%)	NA
Cohort 2	48/48 (100.0%) (92.6% – 100.0%)	49/49 (100.0%) (92.7% – 100.0%)	NA
Cohort 3	50/50 (100.0%) (92.9% – 100.0%)	49/49 (100.0%) (92.7% – 100.0%)	NA
A/Hong Kong (A/H3N2)
Cohort 1	50/50 (100.0%) (92.9% – 100.0%)	52/52 (100.0%) (93.2% – 100.0%)	NA
Cohort 2	48/48 (100.0%) (92.6% – 100.0%)	49/49 (100.0%) (92.7% – 100.0%)	NA
Cohort 3	49/50 (98.0%) (89.4% – 99.9%)	49/49 (100.0%) (92.7% – 100.0%)	0.99
B/Brisbane (B/Victoria)
Cohort 1	46/50 (92.0%) (80.8% – 97.8%)	47/52 (90.4%) (79.0% – 96.8%)	0.95
Cohort 2	44/48 (91.7%) (80.0% – 97.7%)	44/49 (89.8%) (77.8% – 96.6%)	0.97
Cohort 3	48/50 (96.0%) (86.3% – 99.5%)	36/49 (73.5%) (58.9% – 85.1%)	0.004
B/Phuket (B/Yamagata)
Cohort 1	44/50 (88.0%) (75.7% – 95.5%)	23/52 (44.2%) (30.5% – 58.7%)	<0.01
Cohort 2	42/48 (87.5%) (74.8% – 95.3%)	25/49 (51.0%) (36.3% – 65.6%)	0.0002
Cohort 3	45/50 (90.0%) (78.2% – 96.7%)	10/49 (20.4%) (10.2% – 34.3%)	<0.0001

Data presented as n/N (%) (95% CI)

P value based on chi-square test

Table 5. Geometric Mean Titer 28 days after the last vaccination in the three cohorts

	TetIV Group	TriIV Group	P value
A/Michigan (A/H1N1)
Cohort 1	1245.0 (1016.5–1524.9)	1368.2 (1129.1–1657.9)	0.50
Cohort 2	854.3 (631.8–1155.2)	964.6 (778.2–1195.6)	0.51
Cohort 3	766.4 (561.9–1045.3%)	814.0 (620.6–1067.6)	0.77
A/Hong Kong (A/H3N2)
Cohort 1	2137.8 (1760.5–2596.0)	1884.0 (1536.8–2309.7)	0.37
Cohort 2	2031.9 (1456.4–2834.8	2286.1 (1760.4–2968.8)	0.58
Cohort 3	856.3 (557.7–1314.7)	1111.2 (789.0–1564.9)	0.34
B/Brisbane (B/Victoria)
Cohort 1	232.6 (145.2–372.7)	307.5 (201.5–469.3)	0.38
Cohort 2	169.5 (117.8–243.9)	227.9 (154.6–335.9)	0.27
Cohort 3	211.1 (151.3–294.5)	113.9 (70.8–183.4)	0.04
B/Phuket (B/Yamagata)
Cohort 1	117.9 (80.7–172.5)	27.9 (19.3–40.4)	<0.0001
Cohort 2	88.5 (64.7–121.9)	30.1 (20.7–43.8)	<0.0001
Cohort 3	72.6 (56.6–93.1%)	13.5 (10.1–17.9)	<0.0001

Data Expressed as GMT (95% CI)

P value based on Unpaired T-Test

Figure 2. Adverse events reported post influenza vaccination