Evidence update: GlaxoSmithKline’s inactivated quadrivalent influenza vaccines

Figures & data

Table 1. Examples of impact of B-lineage mismatch on vaccine effectiveness.

Country/Reference	Influenza season	Endpoint (95% CI)
Canada [48]	2011–2012 Influenza A: 48% B/Victoria (matched):22% B/Yamagata (mismatched): 26% B/unknown: 4%	Influenza A(H1N1)pdm09: 80% (CI: 52–92) Influenza A(H3N2): 51% (CI: 10–73) All ages: Influenza B: 51% (CI: 26 − 67) Vaccine-recommended B/Victoria: 71% (CI: 40 − 86) Vaccine-alternate B/Yamagata: 27% (CI: −21–56)
		Age: 1 − 19 years: Influenza B: 44% (−32 − 76) Vaccine-recommended B/Victoria: 91% (CI: 24 − 99) Vaccine-alternate B/Yamagata: −47% (CI: −277–43)
Italy [49]	2011–2012 Influenza A: 79% B/Victoria (matched): 3% B/Yamagata (mismatched): 18%	Overall age-adjusted VE against hospitalization caused by laboratory-confirmed influenza: 41% (CI: −126–84)
	2012 − 2013 Influenza A: 54% B/Victoria (matched): 3% B/Yamagata (mismatched): 43%	Overall age-adjusted VE against hospitalization caused by laboratory-confirmed influenza: 26% (CI: −153–78)
Finland [50]	2007 − 2008 B/Yamagata (mismatched): 100% (all circulating influenza B viruses isolated)	Any influenza: 64% (CI: 23–84) Influenza A: 87% (CI: 39–97) Influenza B: 44% (CI: −32–76)

CI, confidence interval; VE, vaccine effectiveness

Table 2. Vaccine protection and immunogenicity criteria for licensure.

	CHMP (EU)		CBER (US)
	18–60 years	>60 years	<65 years (including pediatric population)	≥65 years
Geometric mean titre	No standard	No standard	No standard	No standard
Seroconversion factor	>2.5	>2	No standard	No standard
Seroconversion rate	>40%	>30%	LL of 95% CI ≥40%	LL of 95% CI ≥30%
Seroprotection rate	>70%	>60%	LL of 95% CI ≥70%	LL of 95% CI ≥60%

Note: Geometric mean titers are obtained by computing the anti-log of the arithmetic mean of the log-transformed inverse titers. Seroconversion factor is defined as the geometric mean of the ratio between post- and pre-vaccination reciprocal hemagglutination inhibition titers. Seroconversion rate is defined as the percentage of subjects who had pre- and post-vaccination titers of <1:10 and ≥1:40, respectively, or a pre-vaccination titer of ≥1:10 and ≥4-fold increase in post-vaccination titer. Seroprotection rate is defined as the percentage of subjects with titer of ≥1:40.

CHMP, Committee for medicinal products for human, EU, Europe; US, United States; LL, lower limit; CI, confidence interval

Figure 1. Adjusted GMT data from D-IIV4 trials (by baseline status). (A) Children Aged 3–17 years. (B) Adults Aged ≥18 years.

Data for the graphs obtained from post-hoc analyses in children aged 3–17 years (NCT01196988) [65] and in adults aged ≥18 years (NCT01204671) [63]; Data below the axes indicate GMT ratio (IIV4/IIV3); CI: confidence interval; D-IIV4: inactivated quadrivalent influenza vaccine (Dresden); GMT: geometric mean titers; IIV3-Victoria: inactivated trivalent influenza vaccine Victoria B lineage; IIV3-Yamagata: inactivated trivalent influenza vaccine Yamagata B lineage.

Figure 2. Adjusted GMT data from Q-IIV4 trials (by baseline status). (A) Children Aged 3–17 years. (B) Adults Aged ≥18 years.

Data for the graphs obtained from post-hoc analyses in children aged 3–17 years (NCT01198756) [69] and in adults aged ≥18 years (NCT01196975) [68]; Data below the axes indicate GMT ratio (IIV4/IIV3); CI: confidence interval; GMT: geometric mean titers; IIV3-Victoria: inactivated trivalent influenza vaccine Victoria B lineage; IIV3-Yamagata: inactivated trivalent influenza vaccine Yamagata B lineage; Q-IIV4: inactivated quadrivalent influenza vaccine (Quebec)

Figure 3. SCR data in baseline seronegative population from D-IIV4 trials. (A) Children Aged 3–17 years. (B) Adults Aged ≥18 years.

Data for the graphs obtained from post-hoc analyses in children aged 3–17 years (NCT01196988) [65] and in adults aged ≥18 years (NCT01204671) [63]. Data below the axes indicate SCR difference (IIV4-IIV3); Seronegative subjects (antibody titer <10 1/DIL) prior to vaccination; SCR = antibody titer ≥40 1/DIL after vaccination; CI: confidence interval; D-IIV4: inactivated quadrivalent influenza vaccine (Dresden); IIV3-Victoria: inactivated trivalent influenza vaccine Victoria B lineage; IIV3-Yamagata: inactivated trivalent influenza vaccine Yamagata B lineage; SCR: seroconversion rate.

Figure 4. SCR data in baseline seronegative population from Q-IIV4 trials. (A) Children Aged 3–17 years. (B) Adults Aged ≥18 years.

Data for the graphs obtained from post-hoc analyses in children aged 3–17 years (NCT01198756) [69] and in adults aged ≥18 years (NCT01196975) [68]; Data below the axes indicate SCR difference (IIV4−IIV3); Seronegative subjects (antibody titer < 10 1/DIL) prior to vaccination; SCR = antibody titer ≥ 40 1/DIL after vaccination; CI: confidence interval; IIV3-Victoria: inactivated trivalent influenza vaccine Victoria B lineage; IIV3-Yamagata: inactivated trivalent influenza vaccine Yamagata B lineage; Q-IIV4: inactivated quadrivalent influenza vaccine (Quebec); SCR: seroconversion rate.

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