Efforts to Improve the Seasonal Influenza Vaccine

Abstract

Influenza viruses infect approximately 20% of the global population annually, resulting in hundreds of thousands of deaths. While there are Food and Drug Administration (FDA) approved antiviral drugs for combating the disease, vaccination remains the best strategy for preventing infection. Due to the rapid mutation rate of influenza viruses, vaccine formulations need to be updated every year to provide adequate protection. In recent years, a great amount of effort has been focused on the development of a universal vaccine capable of eliciting broadly protective immunity. While universal influenza vaccines clearly have the best potential to provide long-lasting protection against influenza viruses, the timeline for their development, as well as the true universality of protection they afford, remains uncertain. In an attempt to reduce influenza disease burden while universal vaccines are developed and tested, many groups are working on a variety of strategies to improve the efficacy of the standard seasonal vaccine. This review will highlight the different techniques and technologies that have been, or are being, developed to improve the seasonal vaccination efforts against influenza viruses.

Preventing an Antigenically Disruptive Mutation in Egg-Based H3N2 Seasonal Influenza Vaccines by Mutational Incompatibility

“…recently developed a dual-HA influenza virus to enable efficient vaccine production in eggs without the need for egg adaptation ( Harding et al., 2017 ). Alternatively, several non-egg-based influenza vaccines have been developed ( Harding and Heaton, 2018 ). Commercialization of cell-based ( CDC, 2018a ) and recombinant influenza vaccines ( CDC, 2018b ) that have been developed during the past decade will hopefully completely replace egg-based seasonal vaccines, albeit even if subject to a slow transition.…”

“…Since the HA RBS partially overlaps with several major antigenic sites ( Wiley et al., 1981 , Wilson et al., 1981 , Wu and Wilson, 2017 ), egg-adaptive mutations can dramatically alter HA antigenicity and reduce the effectiveness of seasonal influenza vaccines ( Raymond et al., 2016 , Skowronski et al., 2014 , Wu et al., 2017b , Zost et al., 2017 ). While such problems can be resolved by cell-based or recombinant influenza vaccines, most influenza vaccines available on the market remain egg based because of low production cost and existing infrastructure for their annual production ( Harding and Heaton, 2018 ).…”

Characterization of Inactivated Influenza Vaccines Used in the Russian National Immunization Program

“…The success of CVV adaptation to replication in chicken embryos may vary significantly depending on the virus strain and production year. Therefore, vaccine manufacturers may face the challenge of insufficient efficiency of vaccine antigen production [11]. In addition to the growth rate in chicken embryos, CVVs may vary in terms of sensitivity to inactivating and cleaving agents, as well as conditions of virion concentrations and treatment of the virus-containing fluid.…”

Next Generation Influenza Vaccines: Looking into the Crystal Ball

“…This represents a major manufacturing challenge for the vaccine industry, considering the currently existing technologies. The review by Harding and Heaton describe in detail the major current vaccine manufacturing approach based on virus replication in embryonated eggs [6]. The authors further analyzed the advantages and drawbacks of this approach, which allows producing over 1.5 billion doses every year [7].…”