Immunogenicity and safety of an intramuscular split-virion quadrivalent inactivated influenza vaccine in individuals aged ≥ 6 months in India

Figures & data

Table 1. Study design, vaccines administered, and participant flow.

Vaccine characteristic or participant category	6–35 months	3–8 years	9–17 years	≥ 18 years
Vaccine formulation	NH 2016/2017	SH 2016	NH 2015/2016	SH 2015
Vaccine dose	2 × 0.25 ml (7.5 µg HA/strain) 28 days apart	2 × 0.5 ml (15 µg HA/strain) 28 days apart	1 × 0.5 ml (15 µg HA/strain)	1 × 0.5 ml (15 µg HA/strain)
Vaccine strains
A(H1N1)	A/California/7/2009 X-179A	A/California/7/2009 X-179A	A/California/7/2009 X-179A	A/California/7/2009 X-179A
A(H3N2)	A/Hong Kong/4801/2014	A/Hong Kong/4801/2014	A/Switzerland/9,715,293/2013 NIB-88	A/South Australia/55/2014 IVR 175
B/Victoria	B/Brisbane/60/2008	B/Brisbane/60/2008	B/Brisbane/60/2008	B/Brisbane/60/2008
B/Yamagata	B/Phuket/3073/2013	B/Phuket/3073/2013	B/Phuket/3073/2013	B/Phuket/3073/2013
Participants
Recruited	100	100	100	100
Voluntarily withdrew	1	1	0	0
Noncompliance with protocol	0	1	1	0
Completed the study	99	98	99	100

The immunogenicity and safety of vaccination with the quadrivalent split-virion trivalent inactivated influenza vaccine was assessed in an open-label trial conducted at eight sites in India between July 27, 2015 and January 27, 2017. Children 6 months to 8 years of age were recruited between August 3 and November 26, 2016. All other participants were recruited between July 27, 2015 and May 5, 2016. The trial was registered under WHO Universal Trial no. U1111-1143–8370. Participants aged < 9 years could not have been previous primed with an influenza vaccine and participants aged ≥ 9 years could not have been vaccinated against influenza within the previous 9 months. All participants or their legal representatives provided written, informed consent. Additional exclusion criteria and are listed in the Supplemental online information. Vaccines were formulated in phosphate-buffered saline, were thimerosal-, preservative-, and adjuvant-free, and were presented in prefilled syringes. Vaccines were administered by intramuscular injection into the thigh or deltoid muscle. The study was approved by the independent ethics committee for each site and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Abbreviations: NH, Northern Hemisphere, SH, Southern Hemisphere.

Figure 1. HAI Antibody response to vaccination with quadrivalent split-virion influenza vaccine. Blood was collected before vaccination (day 0) and 28 days after the last vaccination. Serum hemagglutination (HAI) titers were measured as described previously¹⁶ in all vaccinated subjects with data available and are expressed as 1/dilution. HAI titers under the lower limit of quantitation (10) were assigned a value of 5, and all HAI titers above the upper limit of quantitation (10,240) were assigned a value of 10,240. (A) HAI geometric mean titers (GMTs) and 95% confidence intervals (CIs) were determined from log₁₀-transformed data using Student’s t-distribution with n−1 degrees of freedom, after which antilog transformations were applied to the results of calculations. (B) Geometric mean ratio of the individual post-/pre-vaccination HAI titer ratio (GMTR). (C) Proportion of participants seroconverting or with a significant increase in titer. Seroconversion was defined as a pre-vaccination HAI titer < 10 and a post-vaccination HAI titer ≥ 1:40. A significant increase was defined as a pre-vaccination HAI titer ≥ 10 and a ≥ 4-fold increase in HAI titer between pre- and post-vaccination. Statistical analysis was performed using SAS version 9.4 (SAS Institute, Cary, NC).

Table 2. Solicited reactions.

	n (%)
	6–23 months	24–35 months	3–8 years	9–17 years	18–64 years	≥ 65 years
Solicited reaction	(N = 71)	(N = 29)	(N = 100)	(N = 100)	(N = 70)	(N = 30)
Any	22 (31.0)	2 (6.9)	48 (48.0)	44 (44.0)	20 (28.6)	4 (13.3)
Grade 3	2 (2.8)	0 (0.0)	4 (4.0)	0 (0.0)	0 (0.0)	0 (0.0)
Injection site	11 (15.5)	2 (6.9)	41 (41.0)	36 (36.0)	20 (28.6)	4 (13.3)
Grade 3	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Tenderness/pain	10 (14.1)	2 (6.9)	40(40.0)	35 (35.0)	20 (28.6)	4 (13.3)
Grade 3	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Erythema	1(1.4)	0(0.0)	3(3.0)	4(4.0)	0(0.0)	0(0.0)
Grade 3	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Swelling	2 (2.8)	0 (0.0)	3 (3.0)	4 (4.0)	0 (0.0)	0 (0.0)
Grade 3	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Systemic	14(19.7)	1 (3.4)	17 (17.0)	21 (21.0)	3 (4.3)	1 (3.3)
Grade 3	2 (2.8)	0 (0,0)	4 (4.0)	0 (0.0)	0 (0.0)	0 (0.0)
Fever	9 (12.7)	0 (0.0)	8 (8.2)^a	2 (2.0)^a	0 (0.0)	0 (0.0)
Grade 3	0 (0.0)	0 (0.0)	2 (2.0)^a	0 (0.0)^a	0 (0.0)	0 (0.0)
Vomiting	2(2.8)	-	-	-	-	-
Grade 3	2 (2.8)	-	-	-	-	-
Abnormal crying	1(1.4)	-	-	-	-	-
Grade 3	0 (0.0)	-	-	-	-	-
Drowsiness	1(1.4)	-	-	-	-	-
Grade 3	0 (0.0)	-	-	-	-	-
Loss of appetite	3(4.2)	-	-	-	-	-
Grade 3	0 (0.0)	-	-	-	-	-
Irritability	5(7.0)	-	-	-	-	-
Grade 3	0 (0.0)	-	-	-	-	-
Headache	-	0 (0.0)	4 (4.0)	6 (6.0)	1 (1.4)	0(0.0)
Grade 3	-	0 (0.0)	1 (1.0)	0 (0.0)	0 (0.0)	0 (0.0)
Malaise	-	0 (0.0)	4 (4.0)	7 (7.0)	0 (0.0)	1 (3.3)
Grade 3	-	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Myalgia	-	1(3.4)	9 (9.0)	16 (16.0)	2 (2.9)	1 (3.3)
Grade 3	-	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Shivering	-	0 (0.0)	2 (2.0)	0 (0.0)	0 (0.0)	1 (3.3)
Grade 3	-	0 (0.0)	1 (1.0)	0 (0.0)	0 (0.0)	1 (1.0)

Solicited reactions were collected by participants or their legal representatives on diary cards for up to 7 days after each vaccination and analyzed in all participants vaccinated. Reactions were graded from 1 for the least severe to 3 for the most severe as describe in Table S1 in the Supplemental Online Information.

^aN = 98

Pepin S, Donazzolo Y, Jambrecina A, Salamand C, Saville M. Safety and immunogenicity of aquadrivalent inactivated influenza vaccine in adults. Vaccine. 2013;31:5572–78. doi:10.1016/j.vaccine.2013.08.069.

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