Human Nasal Epithelium Organoids for Assessing Neutralizing Antibodies to a Protective SARS-CoV-2 Virus-like Particle Vaccine
Julio Carrera Montoya,
Simon Collett,
Daniel Fernandez Ruiz,
Linda Earnest,
Melissa A. Edeling,
Ashley Huey Yiing Yap,
Chinn Yi Wong,
James P. Cooney,
Kathryn C. Davidson,
Jason Roberts,
Steven Rockman,
Bang M. Tran,
Julie L. McAuley,
Georgia Deliyannis,
Samantha L. Grimley,
Damian F. J. Purcell,
Shafagh A. Waters,
Dale I. Godfrey,
Dhiraj Hans,
Marc Pellegrini,
Jason M. Mackenzie,
Elizabeth Vincan,
William R. Heath,
Joseph Torresi
Affiliations
Julio Carrera Montoya
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Simon Collett
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Daniel Fernandez Ruiz
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Linda Earnest
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Melissa A. Edeling
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Ashley Huey Yiing Yap
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Chinn Yi Wong
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
James P. Cooney
Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia
Kathryn C. Davidson
Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia
Jason Roberts
Department of Medical Biology, University of Melbourne, Melbourne 3052, Australia
Steven Rockman
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Bang M. Tran
Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Julie L. McAuley
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Georgia Deliyannis
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Samantha L. Grimley
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Damian F. J. Purcell
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Shafagh A. Waters
School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales, Sydney 2052, Australia
Dale I. Godfrey
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Dhiraj Hans
Research, Innovation & Commercialisation, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Parkville 3052, Australia
Marc Pellegrini
Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia
Jason M. Mackenzie
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Elizabeth Vincan
Victorian Infectious Diseases Reference Laboratory, Doherty Institute for Infection and Immunity, Royal Melbourne Hospital, Melbourne 3052, Australia
William R. Heath
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Joseph Torresi
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne 3010, Australia
Existing mRNA COVID-19 vaccines have shown efficacy in reducing severe cases and fatalities. However, their effectiveness against infection caused by emerging SARS-CoV-2 variants has waned considerably, necessitating the development of variant vaccines. Ideally, next-generation vaccines will be capable of eliciting broader and more sustained immune responses to effectively counteract new variants. Additionally, in vitro assays that more closely represent virus neutralization in humans would greatly assist in the analysis of protective vaccine-induced antibody responses. Here, we present findings from a SARS-CoV-2 VLP vaccine encompassing three key structural proteins: Spike (S), Envelope (E), and Membrane (M). The VLP vaccine effectively produced neutralizing antibodies as determined by surrogate virus neutralization test, and induced virus-specific T-cell responses: predominantly CD4+, although CD8+ T cell responses were detected. T cell responses were more prominent with vaccine delivered with AddaVax compared to vaccine alone. The adjuvanted vaccine was completely protective against live virus challenge in mice. Furthermore, we utilized air–liquid-interface (ALI)-differentiated human nasal epithelium (HNE) as an in vitro system, which authentically models human SARS-CoV-2 infection and neutralization. We show that immune sera from VLP-vaccinated mice completely neutralized SARS-CoV-2 virus infection, demonstrating the potential of ALI-HNE to assess vaccine induced Nab.
