Abstract

There is increasing interest in the development of new, ‘universal’ influenza vaccines (UIVs) that––unlike current vaccines––are effective against a broad range of seasonal influenza strains, as well as against novel pandemic viruses. While the existing literature discusses the potential epidemiological benefits of UIVs, it is also important to anticipate their potential unintended population consequences. Using mathematical modelling, we illustrate two such types of adverse consequences. First, by reducing the amount of infection-induced immunity in a population without fully replacing it, a seasonal UIV programme may permit larger pandemics than in the absence of vaccination. Second, the more successful a future UIV programme is in reducing transmission of seasonal influenza, the more vulnerable the population could become to the emergence of a vaccine escape variant. These risks could be mitigated by optimal deployment of any future UIV vaccine: namely, the use of a combined vaccine formulation (incorporating conventional as well as multiple universal antigenic targets) and achieving sufficient population coverage to compensate for any reductions in infection-induced immunity. In the absence of large-scale trials of UIVs, disease-dynamic models can provide helpful, early insights into their potential impact. In future, data from continuing vaccine development will be invaluable in developing robustly predictive modelling approaches.

Highlights

  • Current vaccines against influenza have had considerable impact [1], but their efficacy depends on a close match between the vaccine and the circulating influenza virus, in particular to the immunodominant ‘head’ region of the viral surface protein haemagglutinin (HA)

  • Current vaccines have to be updated regularly to remain effective in the face of viral evolution; they cannot be used for pandemic mitigation, owing to the unpredictability of pandemic viruses and the long development time of current vaccines

  • At low levels of universal’ influenza vaccines (UIVs) coverage, a seasonal UIV programme may increase the pandemic size

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Summary

Introduction

Current vaccines against influenza have had considerable impact [1], but their efficacy depends on a close match between the vaccine and the circulating influenza virus, in particular to the immunodominant ‘head’ region of the viral surface protein haemagglutinin (HA). There has been increasing interest in new vaccines against alternative antigenic targets that can provide more broad, long-lasting protection against seasonal and pandemic influenza viruses [2,3]. Several such ‘universal’ influenza vaccines (UIVs) are currently in development (table 1) [14]; they may offer qualitatively new opportunities for influenza control, raising the prospect of routine vaccination programmes that do not need to be updated as often, while protecting against novel pandemic viruses.

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