Duration of Influenza Vaccine Effectiveness: A Systematic Review, Meta-analysis, and Meta-regression of Test-Negative Design Case-Control Studies

Abstract

Whether influenza vaccination offers protection for the duration of an influenza season has recently been questioned following analysis of data from test-negative design (TND) case-control studies. The published literature was systematically reviewed to identify TND studies which estimated change in vaccine effectiveness (VE) with time since vaccination. Fourteen studies were identified through the literature search as meeting eligibility criteria. Meta-analyses were performed to compare VE 15-90 days after vaccination with 91-180 days. A significant decline in VE was observed for influenza subtype A/H3 (ΔVE -33, 95% CI -57; -12) and type B (ΔVE -19, 95% CI -33; -6). VE declined for influenza subtype A/H1, but this difference was not statistically significant (ΔVE -8, 95% CI -27; 21). A multivariable mixed-effects meta-regression model indicated ΔVE was associated with the proportion of study participants who were cases and the proportion of vaccinated controls (p<0.05). This could reflect biological effects such as vaccine and circulating strain mismatch or herd immunity respectively, or the reduced power of individual TND studies in the later parts of an influenza outbreak. Exploration of new influenza vaccination strategies must be a priority for influenza control, particularly in tropical countries with year-round influenza virus activity.