Influenza Vaccine Effectiveness Estimates among US Department of Defense Adult Beneficiaries over Four Consecutive Influenza Seasons: A Test-Negative Design Study with Different Control Groups

A test-negative design study with different control groups (influenza test-negative controls, non-influenza virus positive controls, and pan-negative controls) was conducted to assess inactivated influenza vaccine effectiveness (VE) in adults aged >= 18 years, 2016-2017 through 2019-2020 influenza seasons. A database was developed from the US Department of Defense Global Respiratory Pathogen Surveillance Program. VE was estimated using a generalized linear mixed model with logit link and binomial distribution, adjusted for confounding effects. A total of 7114 adults including 2543 medically attended, laboratory-confirmed influenza-positive cases were identified. Using influenza test-negative controls, the adjusted VE in adults was 40% [95% confidence interval (CI): 33-46%] overall, including 46% (95% CI: 36-55%) for influenza A(H1N1)pdm09, 32% (95% CI: 19-42%) for influenza A(H3N2), and 54% (95% CI: 44-62%) for influenza B. The age-stratified analysis showed that VE estimates against influenza A(H1N1)pdm09 (34%; 95% CI: -29-66%) and influenza A(H3N2) (6%; 95% CI: -60-45%) were low and non-significant for elderly adults >= 65 years of age. Overall VE estimates against any influenza or by influenza (sub)types in adults were consistent when using influenza test-negative controls, non-influenza virus positive controls, and pan-negative controls. Inactivated influenza vaccination provided moderate protection against influenza virus infection, based on the analysis from a large number of adults aged >= 18 years over multiple influenza seasons.

Automated summary

This study assessed the effectiveness of inactivated influenza vaccine in adults and found that it provided moderate protection against influenza virus infection in multiple seasons. The vaccine showed good effectiveness against influenza A(H1N1)pdm09 and influenza B, but lower effectiveness against influenza A(H3N2).