Pandemic Risk Assessment for a Swine Influenza A Virus in Comparative Human Substrates

Swine influenza A viruses pose a public health concern as novel and circulating strains occasionally spill over into human hosts, with the potential to cause disease. Crucial to preempting these events is the use of a threat assessment framework for human populations. However, established guidelines do not specify what animal models or in vitro substrates should be used. We completed an assessment of a contemporary swine influenza isolate, A/swine/GA/A27480/2019, using animal models and human cell substrates. Infection studies in vivo revealed high replicative ability and a pathogenic phenotype in the swine host with replication corresponding to a complementary study performed in swine primary respiratory epithelial cells. However, replication was limited in human primary cell substrates. This contrasted with our findings in the Calu-3 cell line, which demonstrated a replication profile on par with the 2009 pandemic H1N1 virus. These data suggest selection of models is important for meaningful risk assessment. Article Summary LineA novel swine influenza A virus was rigorously assessed for pandemic potential in animal models and human surrogate culture models, illustrating a wide range in potential public health risk dependent on the model utilized.