Abstract
BACKGROUND: Next-generation influenza vaccines (NGIVs) are in development and have the potential to achieve substantial reductions in influenza burden, with resulting widespread health and economic benefits. The prices at which their market can be sustained and which vaccination strategies may maximise health impact and cost-effectiveness, particularly in low- and middle-income countries, are unknown, yet such an understanding could provide a valuable tool for vaccine development and investment decision-making at a national and global level. To address this evidence gap, we projected the health and economic impact of NGIVs in 186 countries and territories. METHODS AND FINDINGS: We inferred current influenza transmission parameters from World Health Organization (WHO) FluNet data in regions defined by their seasonal influenza timing and positivity, and projected 30 years of influenza epidemics, accounting for demographic changes. We considered vaccines including current seasonal vaccines, vaccines with increased efficacy, duration, and breadth of protection, and universal vaccines, defined in line with WHO Preferred Product Characteristics. We estimated cost-effectiveness of different vaccination scenarios using novel estimates of key health outcomes and costs. NGIVs have the potential to substantially reduce influenza burden: compared to no vaccination, vaccinating 50% of children aged under 18 annually prevented 1.3 (95% uncertainty range (UR): 1.2-1.5) billion infections using current vaccines, 2.6 (95% UR: 2.4-2.9) billion infections using vaccines with improved efficacy or breadth, and 3.0 (95% UR: 2.7-3.3) billion infections using universal vaccines. In many countries, NGIVs were cost-effective at higher prices than typically paid for existing seasonal vaccines. However, tiered prices may be necessary for improved vaccines to be cost-effective in lower income countries. This study is limited by the availability of accurate data on influenza incidence and influenza-associated health outcomes and costs. Furthermore, the model involves simplifying assumptions around vaccination coverage and administration, and does not account for societal costs or budget impact of NGIVs. How NGIVs will compare to the vaccine types considered in this model when developed is unknown. We conducted sensitivity analyses to investigate key model parameters. CONCLUSIONS: This study highlights the considerable potential health and economic benefits of NGIVs, but also the variation in cost-effectiveness between high-income and low- and middle-income countries. This work provides a framework for long-term global cost-effectiveness evaluations, and the findings can inform a pathway to developing NGIVs and rolling them out globally.