Immunogenicity and safety of an inactivated 2012/2013 trivalent influenza vaccine produced in mammalian cell culture (Optaflu^®)

Figures & data

Table 1. Demographic and baseline characteristics

	Enrolled Subjects ^a
	Age 18–60 y	Age ≥61 y	Total
	n = 63	n = 63	n = 126
Age (years, SD)	37.4 ± 11.4	68.0 ± 4.7	52.7 ± 17.7
Sex
Male n (%)	30 (48)	32 (51)	62 (49)
Female n (%)	33 (52)	31 (49)	64 (51)
Weight (kg, SD)	78.44 ± 14.97	76.35 ± 13.63	77.40 ± 14.30
Height (cm, SD)	173.3 ± 10.6	173.3 ± 9.2	173.3 ± 9.9
BMI (kg/m^2, SD)	26.0 ± 4.0	25.3 ± 3.1	25.7 ± 3.6
Previous seasonal influenza vaccination
No n (%)	43 (68)	30 (48)	73 (58)
Yes n (%)	20 (32)	33 (52)	53 (42)
Ethnicity
White n (%)	62 (98)	63 (100)	125 (99)
Native Hawaiian or other Pacific Islander n (%)	1 (2)	0	1 (<1)

^aAll subjects who were enrolled in the study (i.e., attended the first clinical visit).

Figure 1. Inclusion and exclusion of subjects. ^aAdults (≥18–≤60 y); ^belderly (≥61 y); ^cimmunogenicity was analyzed as per protocol using HI and SRH assays according to CHMP criteria; ^dsafety assessment was conducted by collection of any solicited local and systemic reactions and collection of adverse events (adverse events were defined as solicited reactions persisting after day 4 or other than solicited local and systemic reactions reported during the study period); ^eone subject was not available for visit 3 and was therefore excluded from immunogenicity analysis

Table 2. Vaccine Immunogenicity assessment by HI assay

	Subjects^a ≥18 to ≤60 y of age							Subjects^a ≥61 y of age
Strains	A(H1N1)			A(H3N2)		B		A(H1N1)			A(H3N2)		B
Pre vaccination (day1)
GMT^b (95%-CI)^c	40 (26–62)			147 (101–212)		36 (26–48)		47 (34–66)			162 (111–236)		28 (22–37)
HI titer ≥40 ^d (n/N^e, %)	35/63		56%	54/63	86%	34/63	54%	38/62		61%	53/62	85%	25/62	40%
(95%-CI)	(42–68%)			(41–67%)		(41–67%)		(48–73%)			(74–93%)		(28–54%)
Post vaccination (day22)
	CHMP^f							CHMP^f
Seroconversion^g (n/N,%)		19/20	95%	2/2	100%	5/5	100%		6/6	100%	2/2	100%	4/5	80%
Significant increase in antibody titers^h (n/N, %)		27/43	63%	40/61	66%	35/58	60%		30/56	54%	26/60	43%	22/57	39%
Seroconversion or significant increase	>40%	46/63	73%	42/63	67%	40/63	63%	>30%	36/62	58%	28/62	45%	26/62	42%
(95%-CI)		(60–83%)		(54–78%)		(50–75%)			(45–70%)		(32–58%)		(30–55%)
GMT		528		935		201			272		681		101
(95%-CI)		(392–710)		(743–1178)		(155–259)			(211–352)		(533–869)		(78–130)
GM increase^i	>2.5	13		6.38		5.63		>2.0	5.79		4.21		3.54
(95%-CI)		(8.75–20)		(4.5–9.06)		(4.11–7.7)			(4.12–8.12)		(2.96–5.97)		(2.65–4.72)
HI titer ≥40 (n/N, %)	>70%	62/63	98%	63/63	100%	62/63	98%	>60%	62/62	100%	62/62	100%	53/62	85%
(95%-CI)		91–100%		94–100%		91–100%			94–100%		94–100%		74–93%

^a Subjects in per protocol set; ^bGMT, geometric mean titer; ^c95%-CI, 95%- confidence interval; ^dproportion of subjects with a HI titer ≥40; ^en/N, subject with a respective immune response (n) as part of the number of subjects of the (sub-) population (N); ^fCHMP, Criteria according to the Committee for Medicinal Products for Human Use; ^gSeroconversion, proportion of subjects with antibody increase from <10 pre vaccination to ≥40 post vaccination; ^hsignificant increase, proportion of subjects with an antibody titer of ≥10 pre vaccination and at least 4-fold antibody increase post vaccination; ⁱGM increase, geometric mean increase.

Table 3. Local injection site and systemic reactions

		Number (%) of subjects ^a
		18–60 y	≥61 y	Total
		(n = 63)	(n = 63)	(n = 126)
Any		45 (71%)	31 (49%)	76 (60%)
Injection site reactions (Day 1 – Day 4 post vaccination)
Any		30 (48%)	22 (35%)	52 (41%)
Ecchymosis (mm)	Any	1 (2%)	4 (6%)	5 (4%)
	>50 mm	0	0	0
Erythema (mm)	Any	1 (2%)	0	1 (1%)
	>50 mm	0	0	0
Induration (mm)	Any	0	2 (3%)	2 (2%)
	>50 mm	0	0	0
Swelling (mm)	Any	1 (2%)	2 (3%)	3 (2%)
	>50 mm	0	0	0
Pain	Any	29 (46%)	17 (27%)	46 (37%)
	Severe	0	0	0
Systemic reactions (Day 1–Day 4 post vaccination)
Any		39 (62%)	20 (32%)	59 (47%)
Chills/ shivering	Any	1 (2%)	1 (2%)	2 (2%)
	Severe	0	0	0
Malaise	Any	5 (8%)	2 (3%)	7 (6%)
	Severe	0	0	0
Myalgia	Any	27 (43%)	12 (19%)	39 (31%)
	Severe	0	0	0
Arthralgia	Any	2 (3%)	0	2 (2%
	Severe	0	0	0
Headache	Any	13 (21%)	4 (6%)	17 (13%)
	Severe	0	0	0
Sweating	Any	10 (16%)	7 (11%)	17 (13%)
	Severe	0	0	0
Fatigue	Any	15 (24%)	7 (11%)	22 (17%)
	Severe	0	0	0
Fever		0	0	0
Other reactions
Temperature	<36 °C	3 (5%)	11 (17%)	14 (11%)
	≥40	0	0	0

^a Local injection site and systemic reactions were recorded for all subjects who provided post vaccination safety data (safety set)

Table 4. Overview of subjects with other adverse events

	Number (%) of subjects ^a
	18–60 y	≥61 y	Total
	(n = 63)	(n = 63)	(n = 126)
Any AEs	9 (14%)	12 (19%)	21 (17%)
At least possibly related AEs	5 (8%)	7 (11%)	12 (10%)
Serious AEs	0	0	0
At least possibly related SAEs	0	0	0
AEs leading to withdrawal	0	0	0

^aOther adverse events were recorded for all subjects who provided post vaccination safety data (safety set)