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Objectives: Vaccination has proven to be an efficient preventive strategy against influenza infection. Each year, two genetically distinct influenza B lineages cocirculate. Current trivalent influenza vaccines (TIVs) contain only one influenza B and two influenza A strains, but vaccine mismatch are frequent due to the difficulty to predict which B lineage will predominate during the next epidemic. Recently licensed quadrivalent influenza vaccines (QIVs) containing a strain from each B lineage should address these issues, but their impact still needs to be estimated. Our study assesses retrospectively what would have been the public health benefit of routinely vaccinating the US population with QIV instead of TIV. Methods: We developed a dynamic compartmental model able to account for interactions between influenza B lineages (natural or vaccine-induced). The model simulates influenza dynamics for the period 2000-2014, to account for the long-term impact of infection and vaccination. Age-structured population dynamics, vaccine efficacy (VE) per strain, and weekly ramp-up of vaccination coverage are modelled. Sensitivity analyses were performed on VE, duration of immunity, levels of vaccine-induced cross-protection between B strains. Results: Assuming a cross-protection of 70% of the matched VE, the model predicts that QIV would have prevented on average 15% more B-lineages cases. Elderly people (65+yo) and young seniors (50-64yo) benefit the most from QIV with 21% and 18% reduction of B cases respectively in those age groups. Reducing the cross-protection estimate of the matched VE to 50%, 30%, and 0% improves the relative benefit of QIV to 25%, 30%, and 34% fewer B cases in the US. Conclusions: Using a realistic retrospective framework, with real-life vaccine mismatch, our analysis shows that routine vaccination with QIV has the potential to substantially reduce the number of influenza infections, even with relatively conservative estimates of TIV induced cross-protection.

Objectives: Trivalent influenza vaccine (TIV) contains two Influenza A strains, but only one of the two B-lineages, resulting in frequent mismatches between vaccines and circulating B-lineages during seasonal epidemics. Quadrivalent influenza vaccine (QIV) prevents such mismatches by including both B-lineages. The objective of our study was to estimate the cost-effectiveness (CE) of QIV versus TIV in Germany by coupling influenza incidence generated by a dynamic individualbased simulation to health and economic outcomes. Methods: An individualbased simulation tool (known in the literature as 4FLU) was refined to estimate the impact of TIV and QIV on clinical infection incidence per year and age over 20 calendar years in Germany. Cases were subsequently linked to health and economic outcomes. Inputs were gathered from national databases and published literature. Vaccination rates reflect the current coverage in Germany; 2014 was used as the baseline year for costs. The productivity costs (societal perspective) were calculated according to the human capital approach. Costs and effects were discounted at 3% and 1.5%, respectively. Univariate and probabilistic sensitivity analyses were performed. Results: Per 100,000 inhabitants, QIV prevents 6,803 more clinical influenza cases and 6.45 more deaths than TIV, accumulated in 20 years. From the societal perspective, QIV dominates TIV, with € 1,424,323 of cost savings and 152 QALYs gained (98 QALYs by preventing clinical cases and 54 QALYs by avoiding premature mortality). These results are sensitive to changes in perspective, vaccination coverage, vaccine prices, productivity cost approach and discount rates, yet favorable CE remains. Conclusions: Based on our analysis, QIV is expected to be cost-effective, or even cost-saving in Germany. Our results are in line with findings from other studies using dynamic models and for other settings.