Rose Chan, Public Health Agency of Canada

Rose Chan (Presenter)1, Joanne Marie M. Del Rosario2, Sneha Vishwanath3, Simon Frost2,4,5, Sneha B. Sujit2, Sruthika K. Ashokan2, Robert Vendramelli1, Matteo Ferrari2, George W. Carnell2,3, Thang Truong1, Paul Tonks3, Ana Liza Ortiz6, Chloe Huang3, Sebastian Einhauser7, Michael Schachtner7, Benedikt Asbach7, Nigel J. Temperton8, Ron Moss2, Matthew Davies2, David Moss2, Rebecca Kinsley2, Ralf Wagner2, 7,9, Darwyn Kobasa1,10, and Jonathan L. Heeney2,3 Affiliations: 1Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB,Canada 2DIOSynVax, Madingley Road, Cambridge, United Kingdom 3Lab of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom 4London School of Hygiene and Tropical Medicine, London, United Kingdom 5Microsoft Health Futures, Redmond, WA, USA 6Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom 7Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany 8Viral Pseudotype Unit, Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Chatham, United Kingdom 9Institute of Clinical Microbiology & Hygiene, University Hospital, University of Regensburg, Regensburg, Germany 10Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada

Fighting & Responding

The emergence of zoonotic Highly Pathogenic Avian Influenza (HPAI) poses a threat to global agriculture industry and public health due to its wide host range, impact on the poultry industry, and human spillover cases. The H5Nx subtypes, specifically, becomes one of the most concerning strains due to its genetic diversity and rapid evolution, which makes vaccine design a challenging task. To address this, a mRNA-based vaccine, DVX-pan-H5Nx, was designed using the Digitally Optimized Synthetic Vaccine (DIOSynVax) platform based on the HPAI viral hemagglutinin, neuraminidase, and M2 Ion channel sequences that were submitted to GISAID. The DVX-pan-H5Nx vaccine consisted of two computationally designed synthetic mRNA expression strings, which encoded both conserved and unique epitopes that aimed to provide cross-clade, panH5Nx protection. The efficacy of the DVX-pan-H5Nx vaccine was evaluated alongside industry standard Whole Inactivated Vaccines (WIV) using BALB/c mice model. The DVX-pan-H5Nx immunized mice showed equivalent or better survival rates and protection against clinical signs of disease following lethal virus challenge with three different A/H5N1 clades (clade 1, 2.3.4.4b, and 2.3.2.1c) when compared to H5N1 WIVs and WHO WIV candidate. The DVX-pan-H5Nx vaccine candidate could address the gap in pandemic preparedness against the constantly evolving H5Nx pathogens.