Vaccine strategies and development before and during the 1968 H3N2 influenza pandemic

Nearly 60 years ago, in 1968, the global population was confronted with the emerging pandemic influenza A virus (IAV) subtype H3N2 (1968 H3N2pdm). An estimate of up to two million fatalities have been linked to 1968 H3N2pdm, and the H3N2 subtype continues to circulate as seasonal IAV among humans until today. The last IAV pandemic dates back to the year 2009 but concerns about a new IAV pandemic in the near future are increasing. The global spread of H5N1 highly pathogenic avian influenza virus and its spill-over into new mammalian hosts, discovery of novel influenza A virus with zoonotic or even pandemic potential, as well as seasonal influenza viruses undergoing antigenic changes necessitate constant vigilance. Here, we highlight the proactive actions, precautionary measures and vaccination strategies used during the 1968 H3N2 IAV pandemic. Our review highlights the emergence and spread of 1968 H3N2pdm over the course of the pandemic, alongside a delineation of vaccine development before, during and after the 1968 pandemic. Updating these strategies in the context of new findings combined with our experiences during the coronavirus disease 2019 (COVID-19) pandemic is necessary to improve preparedness for the next pandemic. Influenza viruses with zoonotic potential will remain a constant threat to public health, and improving countermeasures and communication to the public is key to limit the pandemic ramifications.