Nidhi Kaushik, Vaccine Infectious Disease Organization

Nidhi Kaushik1 , Natalia Pessoa1 , Yohannes Berhane2 , Yan Zhou1,3 , Bryce Warner1,4 1Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Saskatchewan, Canada 2National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB, Canada 3Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada 4Biochemistry, Microbiology & Immunology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Expressing & Multiplying

Highly pathogenic avian influenza (HPAI) H5 viruses emerged in China in 1996 and have caused over 900 human infections with a case fatality rate exceeding 50%. The Clade 2.3.4.4b H5N1 viruses entered North America in late 2021, leading to extensive outbreaks that killed millions of domestic poultry in Canada and severely impacted wild birds and mammals. Some of these viruses have mutations enhancing their ability to infect mammals, increasing the risk of human infections. Since 2024, multiple dairy cattle herds in the U.S. have been affected, impacting over 1000 herds across 14 states, with 41 human cases linked to dairy cattle. Notably, one H5N1 case in Missouri had no direct link to livestock, suggesting the potential for household transmission. Our work aims to identify genetic determinants that contribute to the increased virulence and transmissibility of contemporary H5Nx HPAI isolates. We are using primary human airway cells in air-liquid interface (ALI) cultures to assess the replicative ability of H5Nx viruses. Replication is assessed by TCID50 and RT-qPCR comparing mammalian and avian H5Nx isolates to human seasonal H1N1. We are also studying the virulence and transmission of a subset of these isolates in the ferret model, a standard model of human influenza infection. Ferret experiments include both virulence assessments and airborne droplet transmission assessment using cages separated by a permeable barrier. Our in vitro studies using human airway cells in ALI cultures indicate that certain H5Nx viruses show efficient early viral replication, similar to H1N1, though with lower peak titers.