Immunogenicity and safety of a split-virion quadrivalent influenza vaccine in adults 18–60 years of age in the Republic of Korea

Figures & data

Table 1. HAI antibody response.

			IIV4				IIV3
		CHMP	A/H1N1	A/H3N2	B Yamagata-lineage (B/Phuket)	B Victoria-lineage (B/Brisbane)	A/H1N1	A/H3N2	B Yamagata-lineage (B/Phuket)	B Victoria-lineage (B/Brisbane)
Measure	Day	criterion^a	N = 199	N = 199	N = 199	N = 199	N = 99	N = 99	N = 99	N = 100
HAI GMT (95% CI)	0		142 (116, 174)	41.6 (34.1, 50.9)	256 (212, 309)	186 (156, 220)	116 (86.1, 155)	35.8 (27.2, 47.0)	219 (166, 290)	139 (107, 180)
	21		583 (516, 658)	483 (406, 574)	1068 (950, 1200)	737 (651, 835)	651 (550, 771)	691 (543, 881)	1105 (933, 1308)	290 (231, 364)
HAI titer < 10, n (%)	0		11 (5.5)	34 (17.1)	3 (1.5)	1 (0.5)	6 (6.1)	20 (20.2)	1 (1.0)	2 (2.0)
GMTR (95% CI)	21/0	> 2.5	4.1 (3.30, 5.09)	11.6 (9.16, 14.7)	4.17 (3.49, 4.98)	3.97 (3.30, 4.78)	5.64 (4.09, 7.76)	19.3 (13.9, 26.8)	5.04 (3.81, 6.67)	2.08 (1.75, 2.48)
Seroprotection^b, % (95% CI)	0		83.4 (77.5, 88.3)	56.3 (49.1, 63.3)	91.5 (86.7, 94.9)	89.4 (84.3, 93.3)	78.8 (69.4, 86.4)	55.6 (45.2, 65.5)	87.9 (79.8, 93.6)	85.0 (76.5, 91.4)
	21	> 70%	99.5 (97.2, 100.0)	98.0 (94.9, 99.4)	100.0 (98.2, 100.0)	100.0 (98.2, 100.0)	100.0 (96.3, 100.0)	99.0 (94.5, 100.0)	100.0 (96.3, 100.0)	97.0 (91.5, 99.4)
Seroconversion or significant increase^c	21/0	> 40%	39.7 (32.8, 46.9)	72.4 (65.6, 78.5)	48.7 (41.6, 55.9)	46.2 (39.2, 53.4)	46.5 (36.4, 56.8)	84.8 (76.2, 91.3)	53.5 (43.2, 63.6)	23.0 (15.2, 32.5)

Abbreviations: CI, confidence interval; CHMP, Committee for Medicinal Products for Human Use of the European Medicines Agency; GMT, geometric mean titer; GMTR, geometric mean of the individual ratios of the post-vaccination (day 21) HAI titer divided by the pre-vaccination (day 0) HAI titer; HAI, hemagglutination inhibition; IIV3, trivalent inactivated influenza vaccine; IIV4, quadrivalent inactivated influenza vaccine.

^a According to the former CHMP Note for Guidance (CPMP/BWP/214/96)¹³.

^b Seroprotection was defined as a HAI titer ≥ 40.

^c Seroconversion was defined as a pre-vaccination (day 0) HAI titer < 10 and a post-vaccination (day 21) HAI titer ≥ 1:40, and a significant increase was defined as a pre-vaccination HAI titer ≥ 10 and a ≥ 4-fold increase in HAI titer.

Table 2. Proportions participants reporting solicited reactions.

			IIV4		IIV3
			(N = 200)		(N = 100)
Type	Reaction	Maximum intensity	n	% (95% CI)	n	% (95% CI)
Injection site	Pain	Any	141	70.5 (63.7, 76.7)	64	64.0 (53.8, 73.4)
		Grade 3	2	1.0 (0.1, 3.6)	0	0.0 (0.0, 3.6)
	Erythema	Any	5	2.5 (0.8, 5.7)	3	3.0 (0.6, 8.5)
		Grade 3	0	0.0 (0.0, 1.8)	0	0.0 (0.0, 3.6)
	Swelling	Any	7	3.5 (1.4, 7.1)	0	0.0 (0.0, 3.6)
		Grade 3	0	0.0 (0.0, 1.8)	0	0.0 (0.0, 3.6)
	Induration	Any	6	3 (1.1, 6.4)	2	2.0 (0.2, 7.0)
		Grade 3	0	0.0 (0.0, 1.8)	0	0.0 (0.0, 3.6)
	Ecchymosis	Any	0	0.0 (0.0, 1.8)	0	0.0 (0.0, 3.6)
		Grade 3	0	0.0 (0.0, 1.8)	0	0.0 (0.0, 3.6)
Systemic	Fever	Any	1	0.5 (0.0, 2.8)	0	0.0 (0.0, 3.6)
		Grade 3	0	0 (0.0, 1.8)	0	0.0 (0.0, 3.6)
	Headache	Any	33	16.5 (11.6, 22.4)	20	20.0 (12.7, 29.2)
		Grade 3	3	1.5 (0.3, 4.3)	2	2.0 (0.2, 7.0)
	Malaise	Any	67	33.5 (27.0, 40.5)	42	42.0 (32.2, 52.3)
		Grade 3	3	1.5 (0.3, 4.3)	1	1.0 (0.0, 5.4)
	Myalgia	Any	102	51.0 (43.9, 58.1)	49	49 (38.9, 59.2)
		Grade 3	3	1.5 (0.3, 4.3)	0	0.0 (0.0, 3.6)
	Shivering	Any	13	6.5 (3.5, 10.9)	6	6.0 (2.2, 12.6)
		Grade 3	0	0 (0.0, 1.8)	0	0.0 (0.0, 3.6)

Solicited reactions were recorded by participants up to 7 days after vaccination on diary cards. Erythema, swelling, induration, and ecchymosis were considered grade 1 for ≥ 25 to ≤ 50 mm, grade 2 for ≥ 51 to ≤ 100 mm, and grade 3 for > 100 mm. Fever was considered grade 1 for ≥ 38.0°C to ≤ 38.4°C, grade 2 for ≥ 38.5°C to ≤ 38.9°C, and grade 3 for ≥ 39.0°C. All other reactions and AEs were considered grade 1 for not interfering with activity, grade 2 for some interference with activity, and grade 3 for significant, preventing daily activity. Abbreviations: CI, confidence interval; IIV3, trivalent inactivated influenza vaccine; IIV4, quadrivalent inactivated influenza vaccine.

Table 3. Solicited reactions in the former CHMP Note for Guidance^a occurring within 3 days of vaccination.

	IIV4		IIV3
	(N = 200)		(N = 100)
Reaction	n	% (95% CI)	n	% (95% CI)
Injection-site induration ≥ 50 mm for ≥ 4 consecutive days	0	0.0 (0.0; 1.8)	0	0.0 (0.0; 3.6)
Injection-site ecchymosis	12	6 (3.1; 10.2)	4	4.0 (1.1; 9.9)
Pyrexia (temperature > 38.0°C) for ≥ 24 h	0	0.0 (0.0; 1.8)	0	0.0 (0.0; 3.6)
Malaise	62	31.0 (24.7; 37.9)	40	40.0 (30.3; 50.3)
Shivering	11	5.5 (2.8; 9.6)	6	6.0 (2.2; 12.6)

Abbreviations: CHMP, Committee for Human Vaccines and Medical Products; CI, confidence interval; IIV3, trivalent inactivated influenza vaccine; IIV4, quadrivalent inactivated influenza vaccine.

^a Former CHMP Note for Guidance (CPMP/BWP/214/96)¹³.