This analysis emphasizes the potentially major public health gain which could be achieved through the use of QIVc. Several studies have highlighted the suboptimal VE of egg-based vaccines against some strains of A(H3N2) (6, 27). While the link between VE reduction and egg-related strain mutations is still poorly understood (28) and remains to be fully investigated, recent studies, in different populations, tend to confirm the clinical benefits (7) of QIVc over QIVe regarding A(H3N2) vaccine strain mismatch. Assessing the strain-specific rVE of QIVc compared to QIVe remains a difficult challenge as egg-adaptation phenomena, while most common on A(H3N2), may also occur on B lineages. However, we used QIVc rVE estimated during the 2017–2018 season, when only the A(H3N2) component of QIVc had been grown in cells and we derived our strain specific VE estimations only from this season. Our analysis relies on retrospective studies (17) performed during the 2017–2018 influenza season when A(H3N2) represented 66% of the influenza positive samples (12). By construction, these analyses were only able to assess non-strain specific QIVc rVE compared to QIVe, and we had to estimate QIVc strain specific VE, assuming that the increased total VE was only linked to an increase of VE against A(H3N2). Also, variations in QIVc rVE are likely to occur due to the changing distribution patterns of circulating influenza strains. Namely, influenza seasons with a highly dominant A(H1N1)pdm09 circulation (2015–2016) will see a low benefit to QIVc compared to QIVe, while others, like 2014–2015, 2016–2017, or 2017–2018, may see a significant one. Hence, analysis on multiple seasons is necessary in order to fully assess the potential “averaged” impact of cell-based vaccines across various realistic epidemiological contexts.
We chose to consider as a base case scenario that a mismatch occurred between the A(H3N2) circulating strain and the egg-based vaccine strain during three seasons. We considered this choice a median scenario between a systematic yearly mismatch and no mismatch at all. In addition, this assumption has a limited impact on our results since 1) we consider the observed influenza strain distribution, and 2) we have analyzed situation when the number of mismatched years was varied from 1 to 5 years and reached qualitatively similar results. In addition, our results are consistent with previous health-economic analysis of QIVc in Europe (UK, Spain, Italy, Germany) (29–31), where QIVc has been shown to be either cost-saving or highly cost-effective.
Our analysis uses a 4-strain SEIR compartmental model with an age-structure. This kind of approach, previously used in several similar analysis (9, 32–34), is key to capture the potential indirect effects of influenza vaccination, accounting for prevented chains of transmission. However, it relies on assumptions regarding age-related contact rate which may be difficult to measure for specific countries. Despite its advantages, our approach suffers from limitations inherent to any modeling exercise. In absence of better estimates, our transmission model assumes that 30% of the population benefits from remaining immunity against influenza based on a British modeling study(14). In addition, uncertainties regarding surveillance-based influenza incidence estimates, or influenza strains circulations in the US will directly impact the epidemiological dynamics reproduced by the model.
Finally, our analysis shows the potential public health benefits of the use of QIVc in the 18-64yo US population during the 2013–2018 period. Results obtained retrospectively may be different from what may be achieved in the future as influenza strain circulation is currently challenging to predict. In particular, given the potential expected benefits, and on-going clinical trials, it is likely that QIVc would be also recommended for the pediatric population, which would certainly reinforce its impact.