Enhanced isolation of influenza viruses in qualified cells improves the probability of well-matched vaccines

Heidi Peck,Vivian Leung,Heidi Trusheim,Hilda Lau,Karen L Laurie,Ian G Barr,Sally Soppe,Steve Rockman,Chantal Baas,Cleve Rynehart

doi:10.1038/s41541-021-00415-3

Abstract

Influenza vaccines are utilised to combat seasonal and pandemic influenza. The key to influenza vaccination currently is the availability of candidate vaccine viruses (CVVs). Ideally, CVVs reflect the antigenic characteristics of the circulating virus, which may vary depending upon the isolation method. For traditional inactivated egg-based vaccines, CVVs are isolated in embryonated chicken eggs, while for cell-culture production, CVV’s are isolated in either embryonated eggs or qualified cell lines. We compared isolation rates, growth characteristics, genetic stability and antigenicity of cell and egg CVV’s derived from the same influenza-positive human clinical respiratory samples collected from 2008–2020. Influenza virus isolation rates in MDCK33016PF cells were twice that of eggs and mutations in the HA protein were common in egg CVVs but rare in cell CVVs. These results indicate that fully cell-based influenza vaccines will improve the choice, match and potentially the effectiveness, of seasonal influenza vaccines compared to egg-based vaccines.

Highlights

Influenza is a highly contagious, febrile respiratory illness that is responsible for an estimated 300,000–650,000 deaths annually[1,2].Vaccination is the most effective treatment to prevent infection
This study demonstrated that human influenza viruses were more readily isolated in the qualified mammalian cell line, MDCK33016PF, than in embryonated hen’s eggs
All subtypes and lineages were isolated at higher levels in MDCK33016PF cells and this remained consistent over the study period (2008–2020), while the isolation rate of viruses in embryonated eggs varied for each subtype and lineage

Summary

Introduction

Influenza is a highly contagious, febrile respiratory illness that is responsible for an estimated 300,000–650,000 deaths annually[1,2].Vaccination is the most effective treatment to prevent infection. For the majority of influenza vaccines that are currently produced, the supply of suitable influenza seed viruses for vaccine production depends on the isolation and propagation of influenza viruses from original clinical respiratory samples (OCS). Influenza vaccines have been produced by propagating the viruses required in embryonated chicken eggs. Clinical samples are directly inoculated into the amniotic or allantoic cavities of eggs[3]. Further manipulations on these initial virus isolates, such as by reassorting with laboratory-adapted viruses, are required to generate high yielding viruses suitable for vaccine production[4]. The isolation and propagation of influenza viruses can be performed in continuous cell culture that has been qualified for use in human vaccines[5]

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