2490. A Phase 1, Randomized, Observer Blind, Antigen and Adjuvant Dosage Finding Study to Evaluate the Safety and Immunogenicity of an Adjuvanted, Trivalent Subunit Influenza Vaccine in Elderly Subjects ≥65 Years of Age

BACKGROUND: Influenza virus infection in the elderly remains one of the ten leading causes of death. One successful strategy to enhance the magnitude of their influenza vaccine immune response has been the addition of the adjuvant MF59(®). METHODS: 196 subjects ≥ 65 years of age were enrolled in a dose ranging study with seven treatment arms to assess the safety and immunogenicity of the current formulation of aTIV compared with aTIV-modified formulations in which the dosage of MF59 was doubled or tripled and/or the dosage of the three influenza virus strains (A/H1N1, A/H3N2, and B) was doubled. Vaccine was administered by single or bilateral deltoid inoculations. The antibody responses to all three influenza virus vaccine strains were compared 21 days after a dose or doses of aTIV or aTIV-modified formulations, as measured by hemagglutination inhibition (HI) assay and microneutralization (MN) assay. RESULTS: In general, HI and MN titers at Day 22 increased to a greater degree with the dosage of MF59 compared with that of HA (HI presented in Figure 1). This was evident when comparing the HI and MN titers where antigen content was a constant 45 μg, but MF59 dose ranged from 9.75, 19.5 to 29.25 mg in a single vaccine dose (Group 1, 2 and 6, respectively). Generally, the highest titers against all strains were evident with the highest MF59 dose (29.25 mg). The relationship of antigen content and immunogenicity of the vaccine was less apparent when comparing titers between groups in which HA antigen content doubled from 45 to 90 μg. Administering the dose of MF59 (19.5 mg) and TIV (90 μg) into either a single arm or dividing between two arms resulted in comparable titers. The incidence of solicited AEs tended to increase with the dose of MF59 and to a lesser degree, antigen. The majority of solicited AEs were mild to moderate in severity. The number of unsolicited AEs were similar across the different dosages used in this trial. CONCLUSION: In elderly subjects ≥65 years of age, increase in MF59 dose is associated with increased immunogenicity against all 3 components of seasonal influenza vaccine. DISCLOSURES: G. Otten, Seqirus: Employee, Salary. V. Matassa, Seqirus: Employee, Salary. M. Ciarlet, Novartis Vaccines: Employee, Salary. B. Leav, Seqirus: Employee and Shareholder, Salary.