Waning Vaccine Protection against Influenza among Department of Defense Adult Beneficiaries in the United States, 2016-2017 through 2019-2020 Influenza Seasons.

The objective of this study was to assess inactivated influenza vaccine effectiveness (VE) by time since vaccination in adults aged ≥ 18 years using a test-negative design. All data were obtained from the US Department of Defense Global Respiratory Pathogen Surveillance Program over four influenza seasons, from 2016-2017 through 2019-2020. Analyses were performed to estimate VE using a generalized linear mixed model with logit link and binomial distribution. The adjusted overall VE against any medically attended, laboratory-confirmed influenza decreased from 50% (95% confidence interval (CI): 41-58%) in adults vaccinated 14 to 74 days prior to the onset of influenza-like illness (ILI), to 39% (95% CI: 31-47%) in adults vaccinated 75 to 134 days prior to the onset of ILI, then to 17% (95% CI: 0-32%) in adults vaccinated 135 to 194 days prior to the onset of ILI. The pattern and magnitude of VE change with increasing time since vaccination differed by influenza (sub)types. Compared to VE against influenza A(H1N1)pdm09 and influenza B, the decrease of VE against influenza A(H3N2) was more pronounced with increasing time since vaccination. In conclusion, based on the analysis of 2536 influenza-positive cases identified from 7058 adults over multiple influenza seasons, the effectiveness of inactivated influenza vaccine wanes within 180 days after 14 days of influenza vaccination.