Evaluation of potential immunogenicity differences between Pandemrix™ and Arepanrix™

Figures & data

Figure 1. Avidity parameters per vaccine group. The end association rate (binding response at the end of the association phase; A), dissociation rate (fraction of complex that remained bound at the end of the dissociation phase; B), dissociation rate constant k_d (C), and correlation between the dissociation rate and the k_d (D) were assessed for serum samples obtained 3 weeks after vaccination from children who received either the D-Pan or Q-Pan vaccine. Bars and error bars represent the means of 2 analysis runs per sample and the standard deviation (s.d.), respectively. HA-specific signals were corrected for background binding on the reference channel and for the signal of the blank. Control, an A(H1N1)pdm09 HA-specific mouse monoclonal antibody. RU, resonance units.

Table 1. HI titers and avidity parameters.

		Geometric Mean (95% CI)		GMR Q-Pan/D-pan
	Data range across groups^@	D-Pan	Q-Pan	(95% or 97.5%CI^#)
HI titers pre-purification	80–3620	929 (677–1273)	814 (590–1122)	0.88 (0.56–1.37)
HI titers purified IgG fraction	57–1280	453 (338–607)	413 (306–556)	0.91 (0.60–1.39)
Association rates (RU)^*	7.7–34.5	15.4 (13.4–17.7)	12.4 (10.8–14.3)	0.81 (0.64–1.01)
Dissociation rates (%)^*	79.2–110.5	94.5 (92.5–96.5)	95.5 (93.5–97.6)	1.01 (0.98–1.05)
kd (s^−1)^†	1.1 × 10^−8–1.7 × 10^−4	—	—	—

^@ Data shown are based on the individual analysis runs, excluding discarded samples.

^# Geometric mean ratios (GMR) were estimated with 95% confidence intervals (CI) for HI titers, and with 97.5% CI for association or dissociation rates (to account for multiplicity).

* Geometric means of association and dissociation rates determined during 2 analysis runs were computed by sample.

^† No statistical analyses were performed for the k_d due to the presence of outliers in the log₁₀-transformed data. RU, resonance units.

Figure 2. Relationship between HI titers and avidity parameters before and after sample purification. Serum samples were obtained 3 weeks after vaccination from children who received either the D-Pan or Q-Pan vaccine. Samples were purified to reduce the fractions of IgM and non-specific protein. End association and dissociation rates were assessed on the serum samples before purification, as well as on the purified IgG fraction (left-hand and right-hand panels, respectively). Symbols represent the averages of 2 analysis runs per sample. The r correlation (indicated in the left-hand corner of each graph) was determined irrespective of the vaccine group. RU, resonance units. HI titer, hemagglutination inhibition titer.

Figure 4. Relationship between end association rates and HI titers after adjustment for the antibody concentration. The correlation between the log₁₀-transformed data of the end association rate and hemagglutination inhibition (HI) titers was assessed after adjustment for the antibody concentration. Serum samples were obtained 3 weeks after vaccination from children who received either the D-Pan or Q-Pan vaccine. Symbols represent the averages of 2 analysis runs per sample. Regression lines were estimated by analysis of covariance modeling. RU, resonance units.

Table 2. Geometric mean (ratio) of the association rate after adjustment for the antibody concentration.

	Geometric mean (95% CI) of the association rate, in RU
Covariate	D-Pan	Q-Pan	GMR D-Pan/Q-Pan (95% CI) of the association rate, in RU
log10HI titer (pre-purification)	15.1 (13.8–16.4)	12.7 (11.7–13.9)	0.84 (0.75–0.96)
log10 HI titer (purified IgG fraction)	15.2 (13.9–16.6)	12.7 (11.6–13.9)	0.83 (0.73–0.95)

GMR, geometric mean ratio.

Figure 3. Distribution of avidity parameters. Distributions of the log₁₀-transformed data for the end association rate (A), dissociation rate (B) and the dissociation rate constant k_d(C) were determined using serum samples obtained 3 weeks after vaccination from children who received either the D-Pan or Q-Pan vaccine. Box-and-whiskers plots represent the medians and interquartile ranges (boxes), and the minimum and maximum values (whiskers). Diamonds and open circles represent means and outliers, respectively. Values above the 75^th percentile + 1.5 IQR, or below the 25^th percentile – 1.5 IQR, were considered outliers. RU, resonance units.