Mechanism of Action

Influenza illness and its complications follow infection with influenza viruses. Global surveillance of influenza identifies yearly antigenic variants. For example, since 1977 antigenic variants of influenza A (H1N1 and H3N2) and influenza B viruses have been in global circulation. Specific levels of HI antibody titers post-vaccination with inactivated influenza virus vaccine have not been correlated with protection from influenza virus. In some human studies, antibody titers of 1:40 or greater have been associated with protection from influenza illness in up to 50% of subjects.^1,2

Antibody against one influenza virus type or subtype confers limited or no protection against another. Furthermore, antibody to one antigenic variant of influenza virus might not protect against a new antigenic variant of the same type or subtype. Frequent development of antigenic variants through antigenic drift is the virologic basis for seasonal epidemics and the reason for the usual change to one or more new strains in each year's influenza vaccine. Therefore, inactivated influenza vaccines are standardized to contain the HA of three strains (i.e., typically two type A and one type B) representing the influenza viruses likely to be circulating in the US during the upcoming winter.

Annual revaccination with the current vaccine is recommended because immunity declines during the year after vaccination and circulating strains of influenza virus change from year to year.³

Clinical Studies

Three randomized, controlled clinical studies of AFLURIA® have evaluated the immune responses (specifically, HI antibody titers) to each virus strain in the vaccine. In these studies, post-vaccination immunogenicity was evaluated on sera obtained 21 days after administration of AFLURIA®. No controlled clinical studies demonstrating a decrease in influenza disease after vaccination with AFLURIA® have been performed.

The US study (Study 1) was a randomized, double-blinded, placebo-controlled, multicenter study in healthy subjects ages 18 to less than 65 years. A total of 1,357 subjects were vaccinated (1,089 subjects with AFLURIA® and 268 with a thimerosal-containing placebo). Subjects receiving AFLURIA® were vaccinated using either a single-dose (preservative-free) or multi-dose (one of three lots) formulation. The evaluable efficacy population consisted of 1,341 subjects (1,077 in the AFLURIA® group and 264 in the placebo group) with complete serological data who had not received any contraindicated medications before the post-vaccination immunogenicity assessment. Among the evaluable efficacy population receiving AFLURIA®, 37.5% were men and 62.5% were women. The mean age of the entire evaluable population receiving AFLURIA® was 38 years; 73% were ages 18 to less than 50 years and 27% were ages 50 to less than 65 years. Additionally, 81% of AFLURIA® recipients were White, 12% Black, and 6% Asian.

In Study 1, the following co-primary immunogenicity endpoints were assessed: 1) the lower bounds of the 2-sided 95% confidence intervals (CI) for the proportion of subjects with HI antibody titers of 1:40 or greater after vaccination, which should exceed 70% for each vaccine antigen strain; and 2) the lower bounds of the 2-sided 95% CI for rates of seroconversion (defined as a 4-fold increase in post-vaccination HI antibody titers from pre-vaccination titers of 1:10 or greater, or an increase in titers from less than 1:10 to 1:40 or greater), which should exceed 40% for each vaccine antigen strain.

In subjects ages 18 to less than 65 years, serum HI antibody responses to AFLURIA® met the pre-specified co-primary endpoint criteria for all three virus strains (Table 3). Clinical lotto-lot consistency was demonstrated for the single-dose (preservative-free) and multi-dose formulations of AFLURIA®, showing that these formulations elicited similar immune responses.

Table 3: Study 1 - Serum HI Antibody Responses in Subjects ≥ 18 to < 65 Years Receiving AFLURIA®

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