Human Nasal Epithelium Organoids for Assessing Neutralizing Antibodies to a Protective SARS-CoV-2 Virus-like Particle Vaccine

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Organoids, Vol 3, Iss 1, Pp 18-31 (2024)
Druh dokumentu: article
ISSN: 2674-1172
DOI: 10.3390/organoids3010002
Popis: 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.
Databáze: Directory of Open Access Journals
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