title: Antigenic characterization of influenza viruses produced using synthetic DNA and novel backbones.
abstract: The global system for manufacturing seasonal influenza vaccines has been developed to respond to the natural evolution of influenza viruses, but the problem of antigenic mismatch continues to be a challenge in certain years. In some years, mismatches arise naturally due to the antigenic drift of circulating viruses after vaccine strain selection has already been made. In other years, antigenic differences between the vaccine virus and circulating viruses are introduced as part of the current system, which relies on the use of egg-adapted isolates as a starting material for candidate vaccine viruses (CVVs). Improving the current process for making vaccine viruses can provide great value. We have previously established a synthetic approach for rapidly generating influenza viruses in a vaccine-approved Madin Darby canine kidney (MDCK) cell line using novel, high-growth backbones that increase virus rescue efficiency and antigen yield. This technology also has the potential to produce viruses that maintain antigenic similarity to the intended reference viruses, depending on the hemagglutinin (HA) and neuraminidase (NA) sequences used for gene synthesis. To demonstrate this utility, we generated a panel of synthetic viruses using HA and NA sequences from recent isolates and showed by hemagglutination inhibition (HI) tests that all synthetic viruses were antigenically-like their conventional egg- or cell-propagated reference strains and there was no impact of the novel backbones on antigenicity. This synthetic approach can be used for the efficient production of CVVs that may be more representative of circulating viruses and may be used for both egg- and cell-based vaccine manufacturing platforms. When combined with mammalian cell culture technology for antigen production, synthetic viruses generated using HA and NA sequences from a non-egg-adapted prototype can help to reduce the potential impact of antigenic differences between vaccine virus and circulating viruses on vaccine effectiveness.
authors.affiliation: Seqirus (previously Novartis Influenza Vaccines), 45 Sidney Street, Cambridge, MA 02139, USA. Electronic address: Pirada.Suphaphiphat@seqirus.com.
authors.forename: Pirada
authors.initials: P
authors.lastname: Suphaphiphat
authors.affiliation: Crick Worldwide Influenza Centre, The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Lynne
authors.initials: L
authors.lastname: Whittaker
authors.affiliation: Seqirus (previously Novartis Influenza Vaccines), 45 Sidney Street, Cambridge, MA 02139, USA.
authors.forename: Ivna
authors.initials: I
authors.lastname: De Souza
authors.affiliation: Crick Worldwide Influenza Centre, The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Rodney S
authors.initials: RS
authors.lastname: Daniels
authors.affiliation: Seqirus (previously Novartis Influenza Vaccines), 45 Sidney Street, Cambridge, MA 02139, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Dormitzer
authors.affiliation: Crick Worldwide Influenza Centre, The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: John W
authors.initials: JW
authors.lastname: McCauley
authors.affiliation: Seqirus (previously Novartis Influenza Vaccines), 45 Sidney Street, Cambridge, MA 02139, USA.
authors.forename: Ethan C
authors.initials: EC
authors.lastname: Settembre
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D004247:DNA / Q000276:immunology; D004285:Dogs; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D009439:Neuraminidase / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology*; D016865:Reassortant Viruses / Q000276:immunology; D059386:Reverse Genetics; D014614:Vaccines, Synthetic / Q000276:immunology; D014776:Virus Cultivation
chemical_list: D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D004247:DNA; D009439:Neuraminidase
keywords: Antigenicity; Hemagglutination inhibition; Synthetic influenza virus