High-Dose Inactivated Flu Vaccine Superior to Standard-Dose in Elderly

PHILADELPHIA, PA—High-dose inactivated influenza vaccine (IIV-HD) demonstrates significantly improved immunogenicity compared to standard-dose inactivated influenza vaccine (IIV-SD) in older adults, reported Carlos DiazGranados MD, MSc, of Sanofi Pasteur, Swiftwater, PA, at IDWeek 2014.

Dr. DiazGranados and colleagues conducted a study comparing these two vaccines because previous studies that found IIV-HD superior to IIV-SD in older adults utilized only hemagglutination inhibition (HAI) antibody titers against egg-propagated vaccine antigens. But the 2012–2013 northern hemisphere influenza season showed high H3N2 activity and mismatch between predominant circulating strains and egg-propagated vaccines. For this reason, study investigators reported “a growing interest in evaluating influenza vaccine immune responses beyond the traditional HAI assay.”

The researchers collected samples from a randomized controlled trial evaluating the efficacy of IIV-HD (60mcg HA per strain) vs. IIV-SD (15mcg HA per strain) in adults aged ≥65 years available for testing, in which one- third of trial participants provided post-vaccination sera. This substudy 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/361/2011 (H3N2) antigen, a viral neutralization assay (NT) using both egg- and cell-propagated A/Victoria/361/2011 (H3N2) antigens, and an enzyme-linked lectin assay (ELLA) for anti-neuraminidase (N2) antibodies. Geometric mean titers (GMT) were estimated for IIV-HD and IIV-SD recipients using weighted averages and were compared as GMT ratios (IIV-HD/IIV-SD). 

The researchers assayed samples from 318 IIV-HD and 357 IIV-SD recipients. 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).

This study, which utilized two additional assays beyond the previously studied HAI assay, confirmed earlier findings that (IIV-HD) confers superior immunogenicity in older adults, as compared to IIV-SD. The link between the “explored antibody titers and vaccine protection against influenza is yet to be established,” Dr. DiazGranados noted.