1059Expanded immunogenicity of high-dose inactivated influenza vaccine compared to standard-dose inactivated influenza vaccine in older adults

Background. Previous studies have demonstrated the superior immunogenicity of high-dose inactivated influenza vaccine (IIV-HD) in older adults compared to standard-dose inactivated influenza vaccine (IIV-SD), as measured by hemagglutination inhibition (HAI) antibody titers against egg-propagated vaccine antigens. The 20122013 northern hemisphere influenza season was characterized by high H3N2 activity and by mismatch between predominant circulating strains and egg-propagated vaccines. There is growing interest in evaluating influenza vaccine immune responses beyond the traditional HAI assay. Methods. Samples collected as part of a randomized controlled trial (NCT01427309, sponsored by Sanofi Pasteur) evaluating the efficacy of IIV-HD vs IIV-SD in adults ≥65 years were available for testing; one third of trial participants provided post-vaccination sera. This sub-study utilized a case-cohort design, in which 675 representative samples collected during the 2012-2013 season of the study (from individuals who either developed polymerase chain reaction/culture confirmed H3N2 influenza illness [N = 123] or belonged to a random subset of 10% of non-cases [N = 552]) were selected for expanded testing. Expanded immunogenicity was assessed with an HAI assay using an MDCK cell-propagated A/Victoria/361 (H3N2) antigen, a viral neutralization assay (NT) using both eggand cell-propagated A/Victoria/361 (H3N2) antigens, and an enzyme-linked lectin assay (ELLA) for anti-neuraminidase (N2) antibodies. Geometric mean titers (GMT) were estimated for IIV-HD and IIVSD recipients using weighted averages and were compared as GMT ratios (IIV-HD/ IIV-SD). Results. Samples from 318 IIV-HD and 357 IIV-SD recipients were assayed. The GMT ratios (and 95% Confidence Intervals) were 1.48 (1.26; 1.73), 1.53 (1.29; 1.82), 1.75 (1.43; 2.15), and 1.42 (1.23; 1.65) for cell-propagated HAI, egg-propagated NT, cell-propagated NT, and N2-ELLA, respectively. The GMT ratio for the full immunogenicity subset (2879 IIV-HD and 2872 IIV-SD recipients) assessed by HAI assay using egg-propagated A/Victoria/361 was 1.82 (1.71; 1.94). Conclusion. IIV-HD is associated with significantly improved immunogenicity compared to IIV-SD in older adults as assessed using a range of different assays. Disclosures. C. Diazgranados, Sanofi Pasteur: Employee, Salary B. Hu, Sanofi Pasteur: Employee, Salary T. Voloshen, Sanofi Pasteur: Employee, Salary A. J. Dunning, Sanofi Pasteur: Employee, Salary H. K. Talbot, Sanofi Pasteur: Research Contractor, Research support; MedImmune: Research Contractor, Research support; Teva: Scientific Advisor, Consulting fee V. Landolfi, Sanofi Pasteur: Employee, Salary