Influenza Vaccines: Successes and Continuing Challenges

Abstract

Influenza vaccines have been available for over 80 years. They have contributed to significant reductions in influenza morbidity and mortality. However, there have been limitations in their effectiveness, in part due to the continuous antigenic evolution of seasonal influenza viruses, but also due to the predominant use of embryonated chicken eggs for their production. The latter furthermore limits their worldwide production timelines and scale. Therefore today, alternative approaches for their design and production are increasingly pursued, with already licensed quadrivalent seasonal influenza vaccines produced in cell cultures, including based on a baculovirus expression system. Next-generation influenza vaccines aim at inducing broader and longer-lasting immune responses to overcome seasonal influenza virus antigenic drift and to timely address the emergence of a new pandemic influenza virus. Tailored approaches target mechanisms to improve vaccine-induced immune responses in individuals with a weakened immune system, in particular older adults.

Keywords: correlates of protection; influenza vaccine; influenza vaccine development; next-generation influenza vaccine.

Figure 1.

Timeline of influenza vaccine history [23–29]. Abbreviations: IAV, influenza A virus; IIV, inactivated influenza vaccine; LAIV, live attenuated influenza vaccine; WHO, World Health Organization.

Figure 2.

Major immunogens of influenza virus. Abbreviations: AB, antibody; bnAB, broadly neutralizing antibody; HA, hemagglutinin; M, matrix protein; NA, neuraminidase; NP, nucleoprotein; P, polymerase; RNP, ribonucleoprotein. Adapted from [49, 50] and created with BioRender.com.