Fluzone® High-Dose (IIV3-HD) is a trivalent, inactivated, split-virus influenza vaccine indicated for use in older adults (≥65 years of age). It contains 60 µg hemagglutinin of each influenza strain, which is four times the hemagglutinin content of standard-dose influenza vaccines, including Fluzone (IIV3-SD). IIV3-HD has been licensed for use in older adults in the US since December 2009 and in Canada since February 2016. Areas covered: In this review, we summarize postlicensure studies on the immunogenicity, safety, and effectiveness of IIV3-HD and estimates of its cost-effectiveness in older adults. We also discuss the potential application of IIV3-HD in adults 50-64 years of age and in individuals who may respond poorly to standard-dose influenza vaccines. Expert commentary: Multiple studies conducted since 2004 have consistently shown that, in older adults, IIV3-HD induces substantially greater antibody responses and better protection against influenza and influenza-associated hospitalization than IIV3-SD. Health economic analyses suggest that IIV3-HD can be a cost-effective alternative to standard-dose trivalent or quadrivalent inactivated influenza vaccines and can even be cost-saving compared to IIV3-SD in older adults. Further investigation of IIV3-HD vaccination as a way to improve immune responses and protection against influenza in immunocompromised individuals is warranted.

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People with diabetes (PWD) have an increased risk of developing influenza-related complications, including pneumonia, abnormal glycemic events, and hospitalization. Annual influenza vaccination is recommended for PWD, but vaccination rates are suboptimal. The study aimed to increase influenza vaccination rate in people with self-reported diabetes. This study was a prospective, 1:1 randomized controlled trial of a 6-month Digital Diabetes Intervention in U.S. adults with diabetes. The intervention group received monthly messages through an online health platform. The control group received no intervention. Difference in self-reported vaccination rates was tested using multivariable logistic regression controlling for demographics and comorbidities. The study was registered at clinicaltrials.gov: NCT03870997. A total of 10,429 participants reported influenza vaccination status (5158 intervention, mean age (±SD) = 46.8 (11.1), 78.5% female; 5271 control, Mean age (±SD) = 46.7 (11.2), 79.4% female). After a 6-month intervention, 64.2% of the intervention arm reported influenza vaccination, vers us 61.1% in the control arm (diff = 3.1, RR = 1.05, 95% CI [1.02, 1.08], p = 0.0013, number needed to treat = 33 to obtain 1 additional vaccination). Completion of one or more intervention messages was associated with up to an 8% increase in vaccination rate (OR 1.27, 95% CI [1.17, 1.38], p < 0.0001). The intervention improved influenza vaccination rates in PWD, suggesting that leveraging new technology to deliver knowledge and information can improve influenza vaccination rates in high-risk populations to reduce public health burden of influenza. Rapid cycle innovation could maximize the effects of these digital interventions in the future with other populations and vaccines.

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