Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates

Simon Collett; Linda Earnest; Julio Carrera Montoya; Melissa A Edeling; Ashley Yap; Chinn Yi Wong; Dale Christiansen; Jason Roberts; Jamie Mumford; Valerie Lecouturier; Vincent Pavot; Sergio Marco; Joon Keit Loi; Cameron Simmons; Shivali A Gulab; Jason M Mackenzie; Aaron Elbourne; Paul A Ramsland; Garth Cameron; Dhiraj Hans; Dale I Godfrey; Joseph Torresi

doi:10.3389/fmicb.2023.1065609

Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates

Front Microbiol. 2023 Jun 7:14:1065609. doi: 10.3389/fmicb.2023.1065609. eCollection 2023.

Authors

Simon Collett¹, Linda Earnest², Julio Carrera Montoya², Melissa A Edeling², Ashley Yap², Chinn Yi Wong², Dale Christiansen², Jason Roberts^{3

4}, Jamie Mumford³, Valerie Lecouturier⁵, Vincent Pavot⁵, Sergio Marco⁵, Joon Keit Loi², Cameron Simmons⁶, Shivali A Gulab^{7

8}, Jason M Mackenzie², Aaron Elbourne¹, Paul A Ramsland^{1

9

10}, Garth Cameron², Dhiraj Hans¹¹, Dale I Godfrey², Joseph Torresi²

Affiliations

¹ School of Science, College of Science, Engineering and Health, RMIT University, Melbourne, VIC, Australia.
² Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, Australia.
³ Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁴ Department of Infectious Diseases, The University of Melbourne at the Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁵ Sanofi-Pasteur, Lyon, France.
⁶ Institute of Vector-Borne Disease, Monash University, Clayton, VIC, Australia.
⁷ Avalia Immunotherapies Limited, Wellington, New Zealand.
⁸ Vaccine Alliance Aotearoa New Zealand, Wellington, New Zealand.
⁹ Department of Surgery Austin Health, University of Melbourne, Heidelberg, VIC, Australia.
¹⁰ Department of Immunology, Central Clinical School, Monash University, Melbourne, VIC, Australia.
¹¹ Research, Innovation and Commercialisation, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia.

Abstract

The development of virus-like particle (VLP) based vaccines for human papillomavirus, hepatitis B and hepatitis E viruses represented a breakthrough in vaccine development. However, for dengue and COVID-19, technical complications, such as an incomplete understanding of the requirements for protective immunity, but also limitations in processes to manufacture VLP vaccines for enveloped viruses to large scale, have hampered VLP vaccine development. Selecting the right adjuvant is also an important consideration to ensure that a VLP vaccine induces protective antibody and T cell responses. For diseases like COVID-19 and dengue fever caused by RNA viruses that exist as families of viral variants with the potential to escape vaccine-induced immunity, the development of more efficacious vaccines is also necessary. Here, we describe the development and characterisation of novel VLP vaccine candidates using SARS-CoV-2 and dengue virus (DENV), containing the major viral structural proteins, as protypes for a novel approach to produce VLP vaccines. The VLPs were characterised by Western immunoblot, enzyme immunoassay, electron and atomic force microscopy, and in vitro and in vivo immunogenicity studies. Microscopy techniques showed proteins self-assemble to form VLPs authentic to native viruses. The inclusion of the glycolipid adjuvant, α-galactosylceramide (α-GalCer) in the vaccine formulation led to high levels of natural killer T (NKT) cell stimulation in vitro, and strong antibody and memory CD8⁺ T cell responses in vivo, demonstrated with SARS-CoV-2, hepatitis C virus (HCV) and DEN VLPs. This study shows our unique vaccine formulation presents a promising, and much needed, new vaccine platform in the fight against infections caused by enveloped RNA viruses.

Keywords: SARS-CoV-2; VLP; adjuvant; arbovirus; flavivirus; hepatitis; immunology; vaccine platform.

Copyright © 2023 Collett, Earnest, Carrera Montoya, Edeling, Yap, Wong, Christiansen, Roberts, Mumford, Lecouturier, Pavot, Marco, Loi, Simmons, Gulab, Mackenzie, Elbourne, Ramsland, Cameron, Hans, Godfrey and Torresi.