Background: Several countries have recently transitioned from the trivalent inactivated influenza vaccine (TIV) to the quadrivalent inactivated influenza vaccine (QIV) in order to outweigh influenza B vaccine-mismatch. However, few studies thus far evaluated its benefits versus the TIV in a systematic manner. Our objective was to compare the QIV VE with lineage-mismatched TIV VE.

Methods: We estimated the 2015-2016, 2017-2018, 2019-2020 end-of season influenza B VE against laboratory-confirmed influenza-like illness (ILI) among community patients, using the test-negative design. VE was estimated for pre-determined age groups and for moving age intervals of 15 years.

Results: Since 2011-2012 season, alternate seasons in Israel were dominated by influenza B circulation. Compared with the lineage-mismatched TIV used during the 2015-2016 and 2017-2018 seasons, the 2019-2020 QIV showed the highest all-ages VE, with VE estimates of 56.9 (95% CI 30.1 to 73.4), 16.5 (95% CI -22.5 to 43.1) and -25.8 (95% CI -85.3 to 14.6) for the 2019-2020, 2017-2018 and 2015-2016 seasons, respectively. The 2019-2020 VE point estimated were the highest for the 0.5-4, 5-17 and 18-44 years age groups and for more 15-year age intervals as compared to the other seasons.

Conclusions: Our results support the rapid transition from the TIV to the QIV.