Effectiveness of 2 Influenza Vaccines in Nationwide Cohorts of Finnish 2-Year-Old Children in the Seasons 2015-2016 Through 2017-2018

Background. From 2015-2016 through 2017-2018, injectable, trivalent inactivated influenza vaccines (IIV3) and a nasal spray, tetravalent live-attenuated influenza vaccine (LAIV4) were used in parallel in Finland. To understand how well vaccination with each vaccine type protected children against influenza under real-life conditions, vaccine effectiveness in 2-year-olds was estimated for all 3 seasons. Methods. Each season, a nationwide register-based cohort study was conducted. The study population comprised 60 088, 60 860, and 60 345 children in 2015-2016, 2016-2017, and 2017-2018, respectively. Laboratory-confirmed influenza was the study outcome. Seasonal influenza vaccination with either LAIV4 or IIV3 was the time-dependent exposure of interest. Vaccine effectiveness was defined as 1 minus the hazard ratio comparing vaccinated with unvaccinated children. Results. From 2015-2016 through 2017-2018, the effectiveness of LAIV4 against influenza of any virus type was estimated at 54.2% (95% confidence interval, 32.2-69.0%), 20.3% (-12.7%, 43.6%), and 30.5% (10.9-45.9%); the corresponding effectiveness of IIV3 was 77.2% (48.9-89.8%), 24.5% (-29.8%, 56.1%), and -20.1% (-61.5%, 10.7%). Neither influenza vaccine clearly excelled in protecting children. The LAIV4 effectiveness against type B was greater than against type A and greater than the IIV3 effectiveness against type B. Conclusions. To understand how influenza vaccines could be improved, vaccine effectiveness must be analyzed by vaccine and virus type. Effectiveness estimates also expressing overall protection levels are needed to guide individual and programmatic decision-making processes. Supported by this analysis, the vaccination program in Finland now recommends LAIV4 and injectable, tetravalent inactivated influenza vaccines replacing IIV3.