Message in a bottle: mRNA vaccination for influenza

Abstract

Current influenza vaccines, while being the best method of managing viral outbreaks, have several major drawbacks that prevent them from being wholly-effective. They need to be updated regularly and require extensive resources to develop. When considering alternatives, the recent deployment of mRNA vaccines for SARS-CoV-2 has created a unique opportunity to evaluate a new platform for seasonal and pandemic influenza vaccines. The mRNA format has previously been examined for application to influenza and promising data suggest it may be a viable format for next-generation influenza vaccines. Here, we discuss the prospect of shifting global influenza vaccination efforts to an mRNA-based system that might allow better control over the product and immune responses and could aid in the development of a universal vaccine.

New Vaccine Platforms—Novel Dimensions of Economic and Societal Value and Their Measurement

“…Because viruses (including influenza viruses) continuously adapt and evolve, the WHO uses global surveillance data from the previous 5 to 8 months to update their vaccine recommendations each February for the Northern Hemisphere and each September for the Southern Hemisphere—approximately 6 to 9 months before vaccine deployment [ 28 , 30 ]. The lengthy lead time is also associated with traditional vaccine development approaches needing live cell cultures to grow large amounts of the virus that are then inactivated or attenuated [ 20 , 30 , 31 , 32 , 33 ]. The implication of this prolonged development timeline is that predictions for the upcoming season’s strains (which are based on analyses of region-specific epidemiologic, genetic, and antigenic data, as well as vaccine effectiveness models) are at risk of becoming outdated [ 30 , 34 ].…”

Influenza and Universal Vaccine Research in China

“…Nonhuman primates have responded well to lipid nanoparticle-delivered mRNA vaccines, showing a sustained humoral immune response. In the last decade, mRNA vaccine production and delivery technologies have improved significantly, and it has become possible to design and develop a universal influenza mRNA vaccine [ 102 ]. However, mRNA is extremely unstable and susceptible to degradation in the environment, and mRNA vaccines need to be stored at −80 °C, which makes maintaining the cold chain extremely difficult.…”

mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020

“…The viruses included in the seasonal vaccine each year are chosen based on predictions of which viral clades will be dominant or emerging in the upcoming year, but because of the time it takes to manufacture large quantities of the vaccine, this selection occurs ~6-months prior to the release of the vaccines ( 14 , 19 ). Over that period the viruses in circulation can antigenically drift from the selected strain, leading to an immunologic mismatch between the vaccine and the viruses in circulation ( 13 , 14 , 17 , 20 ). This was exemplified in the 2018-2019 influenza season, in which a vaccine mismatch resulted in a low protective efficacy of ~41% against H1N1 viruses, and ~9% against H3N2 viruses ( 19 , 21 , 22 ).…”