Reduced Effectiveness of Repeat Influenza Vaccination: Distinguishing Among Within-Season Waning, Recent Clinical Infection, and Subclinical Infection

Abstract

Abstract Studies have reported that prior-season influenza vaccination is associated with higher risk of clinical influenza infection among vaccinees. This effect might arise from incomplete consideration of within-season waning and recent infection. Using data from the US Flu Vaccine Effectiveness Network (2011–2012 to 2018–2019 seasons), we found that repeat vaccinees were vaccinated earlier in a season by 1 week. After accounting for waning VE, we determined that repeat vaccinees were still more likely to test positive for A(H3N2) (odds ratio, 1.11; 95% CI, 1.02–1.21) but not influenza B or A(H1N1). We documented clinical infection influenced individuals' decision to vaccinate in the following season while protecting against clinical infection of the same type/subtype. However, adjusting for recent documented clinical infections did not strongly influence the estimated effect of prior-season vaccination. In contrast, we found that adjusting for subclinical or undocumented infection could theoretically attenuate this effect. Additional investigation is needed to determine the impact of subclinical infections on vaccine effectiveness.