Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates
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 protecti...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-06-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1065609/full |
| _version_ | 1797809876388282368 |
|---|---|
| author | Simon Collett Linda Earnest Julio Carrera Montoya Melissa A. Edeling Ashley Yap Chinn Yi Wong Dale Christiansen Jason Roberts Jason Roberts Jamie Mumford Valerie Lecouturier Vincent Pavot Sergio Marco Joon Keit Loi Cameron Simmons Shivali A. Gulab Shivali A. Gulab Jason M. Mackenzie Aaron Elbourne Paul A. Ramsland Paul A. Ramsland Paul A. Ramsland Garth Cameron Dhiraj Hans Dale I. Godfrey Joseph Torresi |
| author_facet | Simon Collett Linda Earnest Julio Carrera Montoya Melissa A. Edeling Ashley Yap Chinn Yi Wong Dale Christiansen Jason Roberts Jason Roberts Jamie Mumford Valerie Lecouturier Vincent Pavot Sergio Marco Joon Keit Loi Cameron Simmons Shivali A. Gulab Shivali A. Gulab Jason M. Mackenzie Aaron Elbourne Paul A. Ramsland Paul A. Ramsland Paul A. Ramsland Garth Cameron Dhiraj Hans Dale I. Godfrey Joseph Torresi |
| author_sort | Simon Collett |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T06:59:30Z |
| format | Article |
| id | doaj.art-db5da8de105e44ddb37fe0edcbcb6989 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-13T06:59:30Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-db5da8de105e44ddb37fe0edcbcb69892023-06-07T04:44:43ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-06-011410.3389/fmicb.2023.10656091065609Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidatesSimon Collett0Linda Earnest1Julio Carrera Montoya2Melissa A. Edeling3Ashley Yap4Chinn Yi Wong5Dale Christiansen6Jason Roberts7Jason Roberts8Jamie Mumford9Valerie Lecouturier10Vincent Pavot11Sergio Marco12Joon Keit Loi13Cameron Simmons14Shivali A. Gulab15Shivali A. Gulab16Jason M. Mackenzie17Aaron Elbourne18Paul A. Ramsland19Paul A. Ramsland20Paul A. Ramsland21Garth Cameron22Dhiraj Hans23Dale I. Godfrey24Joseph Torresi25School of Science, College of Science, Engineering and Health, RMIT University, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaVictorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaDepartment of Infectious Diseases, The University of Melbourne at the Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaVictorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaSanofi-Pasteur, Lyon, FranceSanofi-Pasteur, Lyon, FranceSanofi-Pasteur, Lyon, FranceDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaInstitute of Vector-Borne Disease, Monash University, Clayton, VIC, AustraliaAvalia Immunotherapies Limited, Wellington, New ZealandVaccine Alliance Aotearoa New Zealand, Wellington, New ZealandDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaSchool of Science, College of Science, Engineering and Health, RMIT University, Melbourne, VIC, AustraliaSchool of Science, College of Science, Engineering and Health, RMIT University, Melbourne, VIC, AustraliaDepartment of Surgery Austin Health, University of Melbourne, Heidelberg, VIC, Australia0Department of Immunology, Central Clinical School, Monash University, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, Australia1Research, Innovation and Commercialisation, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, AustraliaThe 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.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1065609/fullflavivirusarbovirusadjuvantVLPimmunologySARS-CoV-2 |
| spellingShingle | Simon Collett Linda Earnest Julio Carrera Montoya Melissa A. Edeling Ashley Yap Chinn Yi Wong Dale Christiansen Jason Roberts Jason Roberts Jamie Mumford Valerie Lecouturier Vincent Pavot Sergio Marco Joon Keit Loi Cameron Simmons Shivali A. Gulab Shivali A. Gulab Jason M. Mackenzie Aaron Elbourne Paul A. Ramsland Paul A. Ramsland Paul A. Ramsland Garth Cameron Dhiraj Hans Dale I. Godfrey Joseph Torresi Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates Frontiers in Microbiology flavivirus arbovirus adjuvant VLP immunology SARS-CoV-2 |
| title | Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates |
| title_full | Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates |
| title_fullStr | Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates |
| title_full_unstemmed | Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates |
| title_short | Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates |
| title_sort | development of virus like particles with inbuilt immunostimulatory properties as vaccine candidates |
| topic | flavivirus arbovirus adjuvant VLP immunology SARS-CoV-2 |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1065609/full |
| work_keys_str_mv | AT simoncollett developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT lindaearnest developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT juliocarreramontoya developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT melissaaedeling developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT ashleyyap developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT chinnyiwong developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT dalechristiansen developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT jasonroberts developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT jasonroberts developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT jamiemumford developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT valerielecouturier developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT vincentpavot developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT sergiomarco developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT joonkeitloi developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT cameronsimmons developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT shivaliagulab developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT shivaliagulab developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT jasonmmackenzie developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT aaronelbourne developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT paularamsland developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT paularamsland developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT paularamsland developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT garthcameron developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT dhirajhans developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT daleigodfrey developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates AT josephtorresi developmentofviruslikeparticleswithinbuiltimmunostimulatorypropertiesasvaccinecandidates |