Assessment of squalene adjuvanted and non-adjuvanted vaccines against pandemic H1N1 influenza in children 6 months to 17 years of age

Figures & data

Figure 1. Participant flowchart (study 1).

Figure 2. Participant flowchart (study 2).

Table 1. Baseline characteristics of children, according to age and study group

		9 – 17 y			3 – 8 y			6 – 35 mo
		3.8 μg HA + AF03 (n = 49)	7.5 μg HA + AF03 (n = 50)	15 μg HA (n = 52)	3.8 μg HA + AF03 (n = 50)	7.5 μg HA + AF03 (n = 50)	15 μg HA (n = 52)	1.9µg HA + ½ AF03 (n = 96)	3.8 μg HA + ½ AF03 (n = 100)	3.8 μg HA + AF03 (n = 104)	7.5 μg HA (n = 101)
Age at V01 (years or months): mean (SD)		12.7 y. (2.4)	12.9 y. (2.7)	12.5 y. (2.3)	5.6 y. (1.8)	5.6 y. (1.9)	6.1 y. (1.8)	18.4 mo. (10.1)	17.7 mo. (9.8)	18.2 mo. (10.5)	18.0 mo. (10.0)
Male/Female ratio		0.88	1.50	0.93	0.61	1.27	0.73	1.04	0.96	0.96	1.10
Ethnic origin: n Caucasian (%)		48 (98.0)	50 (100)	51 (98.1)	49 (98.0)	50 (100)	52 (100)	94 (97.9)	99 (99)	103 (99.0)	100 (99.0)
Influenza Vaccination in 2008/2009: n (%)	Yes	12 (24.5)	10 (19.2)	9 (18.0)	16 (32.0)	21 (42.0)	19 (36.5)	24 (25.0)	27 (27.0)	31 (29.8)	26 (25.7)
	No	37 (75.5)	42 (80.8)	40 (80.0)	33 (66.0)	29 (58.0)	32 (61.5)	65 (67.7)	67 (67.0)	68 (65.4)	74 (73.3)
	Unknown	0 (0)	0 (0)	1 (2.0)	1 (2.0)	0 (0)	1 (1.9)	3 (3.1)	3 (3.0)	1 (1.0)	0 (0)
	Not applicable	-	-	-	-	-	-	4 (4.2)	3 (3.0)	4 (3.8)	1 (1.0)
Experience influenza infection during the 2008/2009 season: n (%)	Yes No Unknown	0 (0) 47 (95.9) 2 (4.1)	1 (1.9) 51 (98.1) 0 (0)	2 (4.0) 48 (96.0) 0 (0)	6 (12.0) 44 (88.0) 0 (0)	6 (12.0) 44 (88.0) 0 (0)	5 (9.6) 47 (90.4) 0 (0)	1 (1.0) 91 (94.8) 4 (4.2)	1 (1.0) 98 (98.0) 1 (1.0)	1 (1.0) 101 (97.1) 2 (1.9)	3 (3.0) 95 (94.1) 3 (3.0)
Subject in contact with a confirmed and/or probable case of H1N1 within the 8 mo prior to enrollment: n (%)	Yes No Unknown	0 (0) 49 (100) 0 (0)	0 (0) 50 (96.2) 2 (3.8)	0 (0) 46 (92.0) 4 (8.0)	0 (0) 49 (98.0) 1 (2.0)	0 (0) 49 (98.0) 1 (2.0)	0 (0) 51 (98.1) 1 (1.9)	0 (0) 95 (99.0) 1 (1.0)	2 (2.0) 96 (96.0) 2 (2.0)	0 (0) 104 (99.0) 0 (0.0)	0 (0) 100 (99.0) 1 (1.0)

Table 2. Hemagglutination inhibition antibody response against H1N1 influenza 21 d after a single injection of H1N1 vaccine in children aged 3–17 y

		H1N1 vaccine
Age group	Endpoint	3.8 µg + AF03	7.5 µg + AF03	15µg
9–17 y	Seroprotection, % (95%CI)	100 (92.6–100)	100 (92.6–100)	98.1 (89.7–100)
	Seroconversion, % (95%CI)	100 (92.6–100)	100 (92.6–100)	98.1 (89.7–100)
	GMTR day 21/day 0 (95%CI)	177 (130–241)	190 (144–252)	125 (81.9–190)
3–8 y	Seroprotection, % (95%CI)	100 (92.9–100)	100 (92.6–100)	94.0 (83.5–98.7)
	Seroconversion, % (95%CI)	100 (92.9–100)	100 (92.6–100)	94.0 (83.5–98.7)
	GMTR day 21/day 0 (95%CI)	124 (99.6–156)	152 (117–198)	35.0 (24.0–51.1)

Seroprotection, number and proportion with titers ≥ 40; Seroconversion, number and proportion with either a titer Day 0 titer < 10 on and a Day 21 titer ≥ 40, or a Day 0 titer ≥ 10 and ≥ 4-fold rise by Day 21; GMTR, geometric mean titer ratio; CI, confidence interval.

Table 3. Hemagglutination inhibition antibody response against H1N1 influenza in children aged 6 to 35 mo

	1.9 µg HA+ ½ AF03	3.8 µg HA + ½ AF03	3.8 µg HA + AF03	7.5 µg HA
Seroprotection, % (95%CI)
Day 21	96.8 (90.9–99.3)	97.9 (92.7–99.7)	100 (96.3–100)	33.3 (24.0–43.7)
Day 42	100 (96.0–100)	100 (96.1–100)	100 (96.3–100)	97.9 (92.7–99.7)
Seroconversion, % (95%CI)
Day 21	96.8 (90.9–99.3)	97.9 (92.7–99.7)	100 (96.3–100)	33.3 (24.0–43.7)
Day 42	100 (96.0–100)	100 (96.1–100)	100 (96.2–100)	97.9 (92.7–99.7)
GMTR day 21/day 0	44.9 (37.1–54.3)	46.4 (38.9–55.4)	69.7 (60.3–80.5)	4.54 (3.64–5.66)
GMTR day 42/day 0	570 (495–657)	491 (434–557)	696 (624–776)	42.3 (34.3–52.1)

Figure 3. Geometric mean hemagglutination inhibition antibody titer against influenza A (H1N1) 2009 before and after administration of adjuvanted or non-adjuvanted H1N1 vaccine in three age groups of children.

Table 4. Safety data: % participants reporting at least one reaction after 1st or 2nd vaccination

	9 to 17 y		3 to 8 y		6–35 mo
	Adjuvanted groups	15 μg HA	Adjuvanted groups	15 μg HA	Adjuvanted groups	7.5 μg HA
	n = 99	n = 52	n = 101	n = 51	n = 300	n = 101
Solicited reaction, %	98.0	86.5	94.1	80.4	87.3	81.0
Post-injection 1	93.9	75.0	86.1	68.6	72.3	72.0
Post-injection 2	80.6	61.5	80.0	59.2	74.4	61.2
Solicited injection site reaction, %	91.9	76.9	87.1	68.6	67.3	52.0
Post-injection 1	83.8	63.5	79.2	54.9	50.0	39.0
Post-injection 2	71.4	53.8	76.0	51.0	49.8	32.7
Solicited systemic reaction, %	77.8	67.3	68.3	49.0	69.7	64.0
Post-injection 1	66.7	57.7	54.5	37.3	52.0	53.0
Post-injection 2	55.1	34.6	45.0	28.6	56.1	49.0
Unsolicited AE, %	63.6	61.5	61.4	74.5	76.3	75.2
Post-injection 1	52.5	46.2	40.6	60.8	61.0	60.4
Post-injection 2	29.6	28.8	37.0	46.9	51.9	45.9
Unsolicited AR, %	27.3	17.3	21.8	29.4	15.0	13.9
Post-injection 1	23.2	13.5	14.9	23.5	10.3	10.9
Post-injection 2	9.2	3.8	10.0	10.2	7.6	3.1
SAE Between day 0 and day 42, %	0.0	0.0	1.0	2.0	1.0	0.0

Table 5. Reactogenicity of H1N1 vaccine in children less than 3 y: % participants reporting at least one solicited reaction between day 0 and 7 after 1st or 2nd vaccination

Injection site	12–35 mo				6–11 mo
reactions: %	Adjuvanted groups n = 150		7.5 μg HA n = 50		Adjuvanted groups n = 150			7.5 μg HA n = 51
Pain/tenderness*	56.7		38.8		34.9			17.6
Erythema**	41.3		24.5		32.7			17.6
Swelling**	16.7		14.3		12.8			3.9
Induration**	23.3		10.2		28.9			17.6
Ecchymosis**	16.7		16.3		11.4			9.8
Systemic	24–35 mo			12–23 mo			6–11 mo
reactions: %	Adjuvanted groups n = 106	7.5 μg HA n = 40		Adjuvanted groups n = 44		7.5 μg HA n = 10	Adjuvanted groups n = 106		7.5 μg HA n = 40
Fever***	17.0	5.1		25.0		20.0	41.3		13.7
Headache	5.7	5.1		-		-	-		-
Malaise	16.0	25.6		-		-	-		-
Myalgia	21.7	12.8		-		-	-		-
Shivering	15.1	2.6		-		-	-		-
Vomiting	-	-		6.8		0.0	26.2		13.7
Crying abnormal	-	-		43.2		50.0	56.7		52.9
Drowsiness	-	-		31.8		40.0	41.6		33.3
Appetite lost	-	-		61.4		40.0	46.3		49.0
Irritability	-	-		54.5		60.0	64.4		76.5

N, number of subjects. *Injection site tenderness for subjects < 24 mo of age or injection site pain for subjects ≥ 24 mo. **All measureable injection site reactions were reported. ***Fever was defined as rectal temperature ≥ 38°C in subjects aged < 24 mo or axillary temperature ≥ 38°C in subjects aged 24 to 35 mo.