Challenges of Making Effective Influenza Vaccines

Abstract

Seasonal influenza vaccines prevent influenza-related illnesses, hospitalizations, and deaths. However, these vaccines are not as effective as other viral vaccines, and there is clearly room for improvement. Here, we review the history of seasonal influenza vaccines, describe challenges associated with producing influenza vaccine antigens, and discuss the inherent difficulties of updating influenza vaccine strains each influenza season. We argue that seasonal influenza vaccines can be dramatically improved by modernizing antigen production processes and developing models that are better at predicting viral evolution. Resources should be specifically dedicated to improving seasonal influenza vaccines while developing entirely new vaccine platforms.

Keywords: antigenic variation; egg adaptation; immunogenicity; seasonal influenza vaccine; vaccine effectiveness; viral evolution.

Figure 1

Timeline of influenza virus pandemics, subtype circulation, major discoveries, and vaccine development. Abbreviations: HA, hemagglutinin; IIV, inactivated influenza vaccine; LAIV, live attenuated influenza vaccine; NA, neuraminidase.

Figure 2

Cultivation of human influenza viruses in eggs can result in egg-adapted amino acid substitutions in the hemagglutinin (HA) protein. Egg-adapted amino acid substitutions in important HA epitopes can cause an antigenic mismatch between the vaccine strain and circulating viruses. When this happens, antibodies elicited by the vaccine cannot bind and protect against circulating influenza virus strains.