Effect of Previous-Year Vaccination on the Efficacy, Immunogenicity, and Safety of High-Dose Inactivated Influenza Vaccine in Older Adults

Influenza vaccines are recommended annually in the United States for all persons ≥6 months of age who do not have contraindications [1]. This practice is supported by data from a randomized controlled trial (RCT) performed nearly 3 decades ago over 5 influenza seasons that did not find differences in efficacy between primary and repeated vaccinations [2]. However, this study was carried out with inactivated whole-virus influenza vaccines, and its generalizability to other vaccines (including currently used inactivated split-virus influenza vaccines) remains uncertain. In addition, considerable data from recent observational studies [3–7] suggest that previous influenza vaccination may influence the immunogenicity and effectiveness of current-season vaccination, resulting in renewed interest in the topic within the scientific community [8]. A recently completed double-blind RCT ({"type":"clinical-trial","attrs":{"text":"NCT01427309","term_id":"NCT01427309"}}NCT01427309) demonstrated that a high-dose inactivated split-virus influenza vaccine (IIV-HD) was more efficacious than a standard-dose inactivated split-virus influenza vaccine (IIV-SD) in preventing laboratory-confirmed influenza illness in adults ≥65 years of age [9]. The study was performed over 2 consecutive influenza seasons. Reenrollment of first-year participants into the second year was allowed. Reenrolled subjects were rerandomized in the second year; thus, the investigation of carryover effects may be regarded as a nested double-blind RCT allowing the unbiased evaluation of the impact of previous-year influenza vaccine (IIV-HD or IIV-SD) on the effect of IIV-HD (compared to IIV-SD) on safety, immunogenicity, and efficacy in older adults [10].