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

Carlos A DiazGranados, Andrew J Dunning, Corwin A Robertson, H Keipp Talbot, Victoria Landolfi, David P Greenberg, Carlos A DiazGranados, Andrew J Dunning, Corwin A Robertson, H Keipp Talbot, Victoria Landolfi, David P Greenberg

Abstract

Background: High-dose inactivated influenza vaccine (IIV-HD) is an alternative to the standard-dose inactivated influenza vaccine (IIV-SD) in the United States for influenza prevention in older adults. IIV-HD improved efficacy relative to IIV-SD in a randomized controlled trial. Recent observational studies suggest that previous influenza vaccination may influence the immunogenicity and effectiveness of current-season vaccination.

Methods: The original study was a double-blind, randomized trial comparing IIV-HD to IIV-SD in adults aged ≥65 years over 2 influenza seasons. A subset of year 1 (Y1) participants reenrolled in year 2 (Y2), receiving vaccine by random assignment in both years. We evaluated the effect of Y1 vaccination on Y2 relative vaccine efficacy (VE), immunogenicity (hemagglutination inhibition [HAI] titers), and safety among reenrolled participants.

Results: Of 14 500 Y1 participants, 7643 reenrolled in Y2. Relative to participants who received IIV-SD both seasons, VE was higher for IIV-HD vaccinees in Y2 (28.3% overall; 25.1% for Y1 IIV-HD, Y2 IIV-HD; and 31.6% for Y1 IIV-SD, Y2 IIV-HD). In multivariate logistic regression models, Y1 vaccine was not a significant modifier of Y2 VE (P= .43), whereas Y2 IIV-HD remained significantly associated with lower influenza risk (P= .043). Compared to administration of IIV-SD in both years, postvaccination HAI titers were significantly higher for patterns that included IIV-HD in Y2. No safety concerns were raised with IIV-HD revaccination.

Conclusions: IIV-HD is likely to provide clinical benefit over IIV-SD irrespective of previous-season vaccination with IIV-HD or IIV-SD. IIV-HD consistently improved immune responses, and no safety concerns emerged in the context of IIV-HD revaccination.

Keywords: age 80 and older; aged; human influenza vaccines; inactivated vaccines; phase 3 clinical trial.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Forest plot of relative efficacy against laboratory-confirmed influenza illness caused by any strain. Illness corresponds to protocol-defined influenza-like illness in year 2. Vaccine efficacy (VE) is the percent efficacy of the different vaccination patterns relative to the year 1 (Y1) standard-dose inactivated influenza vaccine (IIV-SD), year 2 (Y2) IIV-SD vaccination pattern. Vaccination patterns are based on vaccine assigned at randomization in Y2, and vaccine actually received in Y1. The plot on the right depicts the relative VE estimates for the vaccination patterns; horizontal lines represent the 95% confidence intervals (CIs), and solid squares represent the point estimates. All estimates to the right of the null value of 0 favor the corresponding pattern over the referent. CIs that do not intersect with the null value are statistically significant. Abbreviation: IIV-HD, high-dose inactivated influenza vaccine.
Figure 2.
Figure 2.
Geometric mean titer (GMT) ratios and forest plot. GMT ratios presented are for each vaccination pattern relative to the year 1 (Y1) standard-dose inactivated influenza vaccine (IIV-SD), year 2 (Y2) IIV-SD vaccination pattern. Vaccination patterns are based on vaccine assigned at randomization in Y2, and vaccine actually received in Y1. Samples for assaying were collected approximately 28 days after Y2 vaccination. The plot on the right depicts GMT ratios for each vaccination pattern; horizontal lines represent the 95% confidence intervals (CIs), and solid squares represent the point estimates. All estimates to the right of the null value of 1 favor the corresponding pattern over the referent. CIs that do not intersect with the null value are statistically significant. Abbreviation: IIV-HD, high-dose inactivated influenza vaccine.

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Source: PubMed

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