Maria Teresa Malatesta

This commentary provides an overview of the development of a zoonotic influenza vaccine, in response to the emergence of an H5N1 subtype virus from clade 2.3.4.4b in mid-2020. When development was initiated, the World Health Organization (WHO) had recommended four candidate vaccine viruses; the A/Astrakhan/3212/2020-like strain was selected as it provided good coverage of circulating viruses and, critically, was available. To facilitate regulatory approval, the licence of an existing zoonotic vaccine, Aflunov (A/turkey/Turkey/01/2005)—a pre-pandemic monovalent A/H5N1 adjuvanted with MF59 and manufactured using the egg-based platform—was duplicated, with the plan to submit a variation to the duplicate licence for the strain update. This was supported by a ferret immunogenicity study using pseudoviruses (allowing the work to be conducted at a lower biosafety level), in conjunction with clinical data from the original Aflunov licence application, and a US study (NCT05874713) on another candidate zoonotic vaccine manufactured using the cell-based platform. Qualification batches for characterisation studies were manufactured at-risk, until calibrated, homologous reagents were available, and the final product release and stability studies were conducted, with rolling provision of stability data to health authorities. The vaccine was initially approved with a shorter shelf-life, allowing early distribution in certain countries, with later extension of the shelf-life once data became available. In terms of procurement and logistics, early consultation between the European Commission and EU member states resulted in the award of a Framework Contract for the initial supply of 665,000 doses to 15 states. Learnings from the development of this vaccine may help to improve pandemic readiness in the future.