Bringing influenza vaccines into the 21st century

Abstract

The recent H7N9 influenza outbreak in China highlights the need for influenza vaccine production systems that are robust and can quickly generate substantial quantities of vaccines that target new strains for pandemic and seasonal immunization. Although the influenza vaccine system, a public-private partnership, has been effective in providing vaccines, there are areas for improvement. Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses. New influenza potency assays that no longer require the time-consuming step of generating sheep antisera could further speed vaccine release. Adjuvants that increase the breadth of the elicited immune response and allow dose sparing provide an additional means to increase the number of available vaccine doses. Together these technologies can improve the influenza vaccination system in the near term. In the longer term, disruptive technologies, such as RNA-based flu vaccines and 'universal' flu vaccines, offer a promise of a dramatically improved influenza vaccine system.

Keywords: RNA-based; cell culture; influenza; potency assay; synthetic seed; vaccine.

Figure 1. Broad overview of the (A) current influenza vaccine global system from clinical isolate to final commercial vaccine and (B) anticipated system. Advancements at every step streamline the process, generating a new global system in which information on genetic sequences, antigenicity testing, and release assays rather than materials are the primary items shared, resulting in accelerated and increased vaccine supply. Images courtesy of Debora Cartagena and Brian Judd/James Gathany.

Figure 2. Percentage of patient visits for influenza-like illness in the US for selected seasons and years of mismatch. Chart on patient visits are from the US. Outpatient Influenza-like Illness Surveillance Network, Centers for Disease Control and Prevention (http://www.cdc.gov/flu/weekly/). Mismatch data are from the World Health Organization vaccine formulation recommendation from the relevant years.^,–