Oral Presentation 12th Australasian Virology Society Meeting 2024

Air–Liquid-Interface Human Nasal Epithelium (ALI-HNE) Organoids For Assessing Neutralizing Antibodies To A SARS-Cov-2 Virus-Like Particle Vaccine Candidate (#105)

Julio Carrera Montoya 1 , Simon Collett 1 , Daniel Fernandez Ruiz 1 , Linda Earnest 1 , Melissa A. Edeling 1 , Ashley Huey Yiing Yap 1 , Chinn Yi Wong 1 , James P. Cooney 2 , Kathryn C. Davidson 2 , Jason Roberts 3 , Steven Rockman 4 , Bang M. Tran 5 , Julie L. McAuley 1 , Georgia Deliyannis 1 , Samantha L. Grimley 1 , Damian F. J. Purcell 1 , Shafagh A. Waters 6 , Dale I. Godfrey 1 , Dhiraj Hans 7 , Marc Pellegrini 2 , Jason M. Mackenzie 1 , Elizabeth Vincan 3 , William R. Heath 1 , Joseph Torresi 1
  1. Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
  2. Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, VIC, Australia
  3. Victorian Infectious Diseases Reference Laboratory, Doherty Institute for Infection and Immunity, Royal Melbourne Hospital, Melbourne, VIC, Australia
  4. Vaccine Innovation Unit, Seqirus, Parkville 3052, Australia, Seqirus, Parkville, VIC, Australia
  5. Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  6. School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
  7. Research, Innovation & Commercialisation, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Parkville, VIC, Australia

Existing mRNA COVID-19 vaccines have demonstrated efficacy in reducing severe cases and fatalities. However, their effectiveness against infections caused by emerging SARS-CoV-2 variants has diminished, highlighting the need for the development of alternative vaccines approaches. Next-generation vaccines should ideally elicit broader and more sustained immune responses to effectively counteract new variants. Moreover, the development of in vitro assays that more accurately represent virus neutralization in humans would greatly enhance the analysis of protective vaccine-induced antibody responses. 

In this study, we present findings from a SARS-CoV-2 VLP vaccine that includes three key structural proteins: Spike (S), Envelope (E), and Membrane (M). The VLP vaccine effectively produced neutralising antibodies, as determined by a surrogate virus neutralization test, and induced virus-specific T-cell responses. These responses were predominantly CD4+, although CD8+ T cell responses were also detected. The adjuvanted vaccine provided complete protection against live virus challenge in mice. 

Furthermore, we utilized air–liquid-interface (ALI)-differentiated human nasal epithelium (HNE) as an in vitro system to more authentically model human SARS-CoV-2 infection and neutralisation. Our results show that immune sera from VLP-vaccinated mice completely neutralized SARS-CoV-2 infection, demonstrating the potential of the ALI-HNE system to assess vaccine-induced neutralizing antibodies. These findings underscore the promise of VLP-based vaccines and advanced in-vitro systems in the development of effective next-generation COVID-19 vaccines and other respiratory viruses.