Retrospective Public Health Impact of a Quadrivalent Influenza Vaccine in the United States Over the Period 2000-2014

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.