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To ensure that vaccination offers the best protection against an infectious disease, sequence identity between the vaccine and the circulating strain is paramount. During replication of nucleic acid, random mutations occur due to the level of polymerase fidelity. In traditional influenza vaccine manufacture, vaccine viruses are propagated in fertilized chicken eggs, which can result in egg-adaptive mutations in the antigen-encoding genes. Whilst this improves infection and replication in eggs, mutations may reduce the effectiveness of egg-based influenza vaccines against circulating human viruses. In contrast, egg-adaptive mutations are avoided when vaccine viruses are propagated in Madin-Darby canine kidney (MDCK) cell lines during manufacture of cell-based inactivated influenza vaccines. The first mammalian cell-only strain was included in Flucelvax® Quadrivalent in 2017. A sequence analysis of the viruses selected for inclusion in this vaccine (n = 15 vaccine strains, containing both hemagglutinin and neuraminidase) demonstrated that no mutations occur in the antigenic sites of either hemagglutinin or neuraminidase, indicating that cell adaptation does not occur during production of this cell-based vaccine. The development of this now entirely mammalian-based vaccine system, which incorporates both hemagglutinin and neuraminidase, ensures that the significant protective antigens are equivalent to the strains recommended by the World Health Organization (WHO) in both amino acid sequence and glycosylation pattern. The inclusion of both proteins in a vaccine may provide an advantage over recombinant vaccines containing hemagglutinin alone. Findings from real world effectiveness studies support the use of cell-based influenza vaccines. [ABSTRACT FROM AUTHOR]

To ensure that vaccination offers the best protection against an infectious disease, sequence identity between the vaccine and the circulating strain is paramount. During replication of nucleic acid, random mutations occur due to the level of polymerase fidelity. In traditional influenza vaccine manufacture, vaccine viruses are propagated in fertilized chicken eggs, which can result in egg-adaptive mutations in the antigen-encoding genes. Whilst this improves infection and replication in eggs, mutations may reduce the effectiveness of egg-based influenza vaccines against circulating human viruses. In contrast, egg-adaptive mutations are avoided when vaccine viruses are propagated in Madin-Darby canine kidney (MDCK) cell lines during manufacture of cell-based inactivated influenza vaccines. The first mammalian cell-only strain was included in Flucelvax® Quadrivalent in 2017. A sequence analysis of the viruses selected for inclusion in this vaccine (n = 15 vaccine strains, containing both hemagglutinin and neuraminidase) demonstrated that no mutations occur in the antigenic sites of either hemagglutinin or neuraminidase, indicating that cell adaptation does not occur during production of this cell-based vaccine. The development of this now entirely mammalian-based vaccine system, which incorporates both hemagglutinin and neuraminidase, ensures that the significant protective antigens are equivalent to the strains recommended by the World Health Organization (WHO) in both amino acid sequence and glycosylation pattern. The inclusion of both proteins in a vaccine may provide an advantage over recombinant vaccines containing hemagglutinin alone. Findings from real world effectiveness studies support the use of cell-based influenza vaccines.

Vaccine development has been hampered by the long lead times and the high cost required to reach the market. The 2020 pandemic, caused by a new coronavirus (SARS-CoV-2) that was first reported in late 2019, has seen unprecedented rapid activity to generate a vaccine, which belies the traditional vaccine development cycle. Critically, much of this progress has been leveraged off existing technologies, many of which had their beginnings in influenza vaccine development. This commentary outlines the most promising of the next generation of non-egg-based influenza vaccines including new manufacturing platforms, structure-based antigen design/computational biology, protein-based vaccines including recombinant technologies, nanoparticles, gene- and vector-based technologies, as well as an update on activities around a universal influenza vaccine.

To ensure that vaccination offers the best protection against an infectious disease, sequence identity between the vaccine and the circulating strain is paramount. During replication of nucleic acid, random mutations occur due to the level of polymerase fidelity. In traditional influenza vaccine manufacture, vaccine viruses are propagated in fertilized chicken eggs, which can result in egg-adaptive mutations in the antigen-encoding genes. Whilst this improves infection and replication in eggs, mutations may reduce the effectiveness of egg-based influenza vaccines against circulating human viruses. In contrast, egg-adaptive mutations are avoided when vaccine viruses are propagated in Madin-Darby canine kidney (MDCK) cell lines during manufacture of cell-based inactivated influenza vaccines. The first mammalian cell-only strain was included in Flucelvax ® Quadrivalent in 2017. A sequence analysis of the viruses selected for inclusion in this vaccine ( n = 15 vaccine strains, containing both hemagglutinin and neuraminidase) demonstrated that no mutations occur in the antigenic sites of either hemagglutinin or neuraminidase, indicating that cell adaptation does not occur during production of this cell-based vaccine. The development of this now entirely mammalian-based vaccine system, which incorporates both hemagglutinin and neuraminidase, ensures that the significant protective antigens are equivalent to the strains recommended by the World Health Organization (WHO) in both amino acid sequence and glycosylation pattern. The inclusion of both proteins in a vaccine may provide an advantage over recombinant vaccines containing hemagglutinin alone. Findings from real world effectiveness studies support the use of cell-based influenza vaccines.

Vaccine development has been hampered by the long lead times and the high cost required to reach the market. The 2020 pandemic, caused by a new coronavirus (SARS-CoV-2) that was first reported in late 2019, has seen unprecedented rapid activity to generate a vaccine, which belies the traditional vaccine development cycle. Critically, much of this progress has been leveraged off existing technologies, many of which had their beginnings in influenza vaccine development. This commentary outlines the most promising of the next generation of non-egg-based influenza vaccines including new manufacturing platforms, structure-based antigen design/computational biology, protein-based vaccines including recombinant technologies, nanoparticles, gene- and vector-based technologies, as well as an update on activities around a universal influenza vaccine. [ABSTRACT FROM AUTHOR]