Immunogenicity

Study Summaries   Study 1   Study 2   Study 3

A randomized, double-blinded, placebo-controlled, multicenter, US study in healthy subjects, aged 18 to less than 65 years. A total of 1,357 subjects were vaccinated (1,089 subjects receiving with Afluria^® and 268 receiving with a thimerosal-containing placebo). Subjects receiving Afluria^® were vaccinated using either a single-dose (thimerosal-free) or multi-dose vial (one of 3 lots).

In subjects ages 18 to less than 65 years of age, serum HI antibody responses to Afluria^® met the pre-specified coprimary endpoint criteria for all 3 virus strains (See Table 1). Clinical lot-to-lot consistency was demonstrated for the preservative-free single-dose (thimerosol-free) syringe and multi-dose vial formulations of Afluria^®, showing that these formulations elicited similar immune responses.

Table 1: US Study—Serum Hemagglutination-Inhibiting Antibody Responses in Adults ≥18 to <65 Years Receiving Afluria^®

Treatment Arm	Number Enrolled/ Evaluable	Vaccine Strain	Seroconversion Rate* (95% CI)	HI Titer ≥1:40† (95% CI)
All active Afluria® influenza vaccine formulations‡	1089/1077	H1N1	48.7% (45.6, 51.7)	97.8% (96.7, 98.6)
		H3N2	71.5% (68.7, 74.2)	99.9% (99.5, 100.0)
		B	69.7% (66.9, 72.5)	94.2% (92.7, 95.6)
Placebo	270/264	H1N1	2.3% (0.8, 4.9)	74.6% (68.9, 79.8)
		H3N2	0.0% (N/A)	72.0% (66.1, 77.3)
		B	0.4% (<0.1, 2.1)	47.0% (40.8, 53.2)

*Seroconversion rate is defined as a 4-fold increase in post-vaccination HI titer from pre-vaccination titer ≥1:10, or an increase in titer from <1:10 to ≥1:40. Lower bound of 95% CI for seroconversion should be >40% for the study population.

†HI titer ≥1:40 is defined as the proportion of subjects with a minimum post-vaccination HI titer of 1:40. Lower bound of 95% CI for HI titer ≥1:40 should be >70% for the study population.

‡Active formulations include aggregated results for single-dose (preservative-free) and multi-dose formulations of Afluria^®.

A randomized, controlled, UK study that enrolled 275 healthy adult subjects ages 65 years and older. This study compared Afluria^® with a European-licensed trivalent inactivated influenza vaccine, containing traces of thimerosal, as an active control.

The coprimary immunogenicity endpoints for the seroconversion rate and the proportion of subjects with a minimum post-vaccination HI titer of 1:40 are presented in Table 2.

Table 2: Serum HI Antibody Responses for Subjects ≥65 Years Receiving Afluria^®

Number of Subjects	Vaccine Strain	Seroconversion Rate* (95% CI)	HI Titer ≥1:40† (95% CI)
206	H1N1	34.0% (27.5, 40.9)	85.0% (79.3, 89.5)
	H3N2	44.2% (37.3, 51.2)	99.5% (97.3, 100.0)
	B	45.6% (38.7, 52.7)	77.7% (71.4, 83.2)

*Seroconversion rate is defined as a 4-fold increase in post-vaccination HI antibody titer from pre-vaccination titer ≥1:10, or an increase in titer from <1:10 to ≥1:40. Lower bound of 95% CI for seroconversion should be >30% for the study population.

†HI titer ≥1:40 is defined as the proportion of subjects with a minimum post-vaccination HI antibody titer of 1:40. Lower bound of 95% CI for HI antibody titer ≥1:40 should be >60% for the study population.

A second, randomized, controlled, UK study that enrolled 406 healthy subjects 18 years and older (stratified by age 18 to less than 60 years, and 60 years and older). This study compared Afluria^® with a European-licensed trivalent inactivated influenza vaccine active control.

The post-hoc analysis of serum HI antibody responses showed that the lower bound of the 95% CI for subjects with HI antibody titers of 1:40 or greater after vaccination exceeded 70% for each strain. HI antibody responses were lower in subjects ages 65 years and older after administration of Afluria^®. Serum HI antibody responses to the active control were similar to those for Afluria^® in both age groups.