Preclinical development of a cross-protective β-SARS-CoV-2 virus-like particle vaccine adjuvanted with MF59

preclinical-development-of-a-cross-protective-β-sars-cov-2-virus-like-particle-vaccine-adjuvanted-with-mf59
Preclinical development of a cross-protective β-SARS-CoV-2 virus-like particle vaccine adjuvanted with MF59

Data availability

The data that support the findings of this study are not openly available due to reasons of commercial sensitivity but are available from the corresponding author upon request. Data are located in controlled-access LabArchives data storage at the University of Melbourne.

References

  1. Wang, P. et al. Increased resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to antibody neutralization. https://doi.org/10.1101/2021.1101.1125.428137 (2021).

  2. Davies, N. G. et al. Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature 593, 270–274 (2021).

    Google Scholar 

  3. Qu, P. et al. Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant. Cell Host Microbe 30, 1518–1526 e1514 (2022).

    Google Scholar 

  4. Takashita, E. et al. In vitro efficacy of antiviral agents against omicron subvariant BA.4.6. N. Engl. J. Med. 387, 2094–2097 (2022).

    Google Scholar 

  5. Arora, P. et al. Omicron sublineage BQ.1.1 resistance to monoclonal antibodies. Lancet Infect. Dis. 23, 22–23 (2023).

    Google Scholar 

  6. Voysey, M. et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. https://doi.org/10.1016/S0140-6736(21)00432-3 (2021).

  7. Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).

    Google Scholar 

  8. Uraki, R. et al. Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB. Lancet Infect. Dis. 23, 30–32 (2023).

    Google Scholar 

  9. Kurhade, C. et al. Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1, and XBB.1 by parental mRNA vaccine or a BA.5-bivalent booster. Nat. Med. https://doi.org/10.1038/s41591-022-02162-x (2022).

  10. Planas, D. et al. Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1lineages combining increased fitness and antibody evasion. Nat. Commun. 15, 2254 (2024).

    Google Scholar 

  11. Yang, S. et al. Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure. Lancet Infect. Dis. 24, e70–e72 (2024).

    Google Scholar 

  12. Zou, J. et al. Neutralization of BA.4-BA.5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1with Bivalent Vaccine. N Engl. J. Med. 388, 854–857 (2023).

    Google Scholar 

  13. Chalkias, S. et al. Three-month antibody persistence of a bivalent omicron-containing booster vaccine against COVID-19. Res. Sq. https://doi.org/10.21203/rs.3.rs-2239682/v1 (2022).

  14. Wang, Q. et al. Antibody response to omicron BA.4-BA.5 bivalent booster. N. Engl. J. Med. https://doi.org/10.1056/NEJMc2213907 (2023).

  15. Collier, A. Y. et al. Immunogenicity of BA.5 Bivalent mRNA vaccine boosters. N. Engl. J. Med. https://doi.org/10.1056/NEJMc2213948 (2023).

  16. Fabiani, M. et al. Protection against severe COVID-19 after second booster dose of adapted bivalent (original/Omicron BA.4-5) mRNA vaccine in persons >/=60 years, by time since infection, Italy, 12 September to 11 December 2022. Euro Surveill. 28. https://doi.org/10.2807/1560-7917.ES.2023.28.8.2300105 (2023).

  17. Liu, J. et al. Virological and antigenic characteristics of SARS-CoV-2 variants LF.7.2.1, NP.1, and LP.8.1. Lancet Infect. Dis. 25, e128–e130 (2025).

    Google Scholar 

  18. Guo, C. et al. Antigenic and virological characteristics of SARS-CoV-2 variants BA.3.2, XFG, and NB.1.8.1. Lancet Infect. Dis. 25, e374–e377 (2025).

    Google Scholar 

  19. Addo, I. Y., Dadzie, F. A., Okeke, S. R., Boadi, C. & Boadu, E. F. Duration of immunity following full vaccination against SARS-CoV-2: a systematic review. Arch. Public Health 80, 200 (2022).

    Google Scholar 

  20. Tu, W. et al. SARS-CoV-2 infection, hospitalization, and death in vaccinated and infected individuals by age groups in Indiana, 2021‒2022. Am. J. Public Health 113, 96–104 (2023).

    Google Scholar 

  21. Mesle, M. M. I. et al. Estimated number of lives directly saved by COVID-19 vaccination programmes in the WHO European Region from December, 2020, to March, 2023: a retrospective surveillance study. Lancet Respir. Med. 12, 714–727 (2024).

    Google Scholar 

  22. Link-Gelles, R. et al. Interim estimates of 2024-2025 COVID-19 vaccine effectiveness among adults aged >/=18 Years—VISION and IVY networks, September 2024–January 2025. Morb. Mortal. Wkly Rep. 74, 73–82 (2025).

    Google Scholar 

  23. Suryawanshi, R. K. et al. Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination. Nature 607, 351–355 (2022).

    Google Scholar 

  24. Collett, S. et al. Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates. Front. Microbiol. 14, 1065609 (2023).

    Google Scholar 

  25. Sekine, T. et al. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell 183, 158–168 e114 (2020).

    Google Scholar 

  26. Grifoni, A. et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 181, 1489–1501 e1415 (2020).

    Google Scholar 

  27. Sette, A. & Crotty, S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell 184, 861–880 (2021).

    Google Scholar 

  28. Tarke, A. et al. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. Cell 185, 847–859 e811 (2022).

    Google Scholar 

  29. Augusto, D. G. et al. A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection. Nature 620, 128–136 (2023).

    Google Scholar 

  30. Chalkias, S. et al. A bivalent omicron-containing booster vaccine against Covid-19. N. Engl. J. Med. 387, 1279–1291 (2022).

    Google Scholar 

  31. Li, Q. et al. Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses. Signal Transduct. Target. Ther. 7, 256 (2022).

    Google Scholar 

  32. Moyo-Gwete, T. et al. Shared N417-dependent epitope on the SARS-CoV-2 Omicron, Beta, and Delta Plus variants. J. Virol. 96, e0055822 (2022).

    Google Scholar 

  33. Launay, O. et al. Immunogenicity and safety of beta-adjuvanted recombinant booster vaccine. N. Engl. J. Med 387, 374–376 (2022).

    Google Scholar 

  34. Choi, A. et al. Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters inhealthy adults: an interim analysis. Nat. Med. 27, 2025–2531 (2021).

    Google Scholar 

  35. Klinakis, A., Cournia, Z. & Rampias, T. N-terminal domain mutations of the spike protein are structurally implicated in epitope recognition in emerging SARS-CoV-2 strains. Comput. Struct. Biotechnol. J. 19, 5556–5567 (2021).

    Google Scholar 

  36. Dacon, C. et al. Broadly neutralizing antibodies target the coronavirus fusion peptide. Science 377, 728–735 (2022).

    Google Scholar 

  37. Edeling, M. A. et al. Development of methods to produce SARS-CoV-2 virus-like particles at scale. Biotechnol. Bioeng. https://doi.org/10.1002/bit.28937 (2025).

  38. Hsieh, C. L. et al. Structure-based design of prefusion-stabilized SARS-CoV-2 spikes. Science 369, 1501–1505 (2020).

    Google Scholar 

  39. Carrera Montoya, J. et al. Human nasal epithelium organoids for assessing neutralizing antibodies to a protective SARS-CoV-2 virus-like particle vaccine. Organoids 3, 0–13 (2024).

    Google Scholar 

  40. Melbourne, T. U. o. Stabilised virus-like particles and uses there of. Australian Provisional Patent Application No. 2024903881 (2024).

  41. Townsend, J. A. et al. Differences in oligomerization of the SARS-CoV-2 envelope protein, poliovirus VP4, and HIV Vpu. Biochemistry 63, 241–250 (2024).

    Google Scholar 

  42. Mandala, V. S. et al. Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers. Nat. Struct. Mol. Biol. 27, 1202–1208 (2020).

    Google Scholar 

  43. Zhang, R. et al. Dimeric transmembrane structure of the SARS-CoV-2 E protein. Commun. Biol. 6, 1109 (2023).

    Google Scholar 

  44. Tan, C. W. et al. A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Nat. Biotechnol. 38, 1073–1078 (2020).

    Google Scholar 

  45. Tan, C. W. et al. Pan-sarbecovirus neutralizing antibodies in BNT162b2-immunized SARS-CoV-1 survivors. N. Engl. J. Med. 385, 1401–1406 (2021).

    Google Scholar 

  46. Zhuang, Z. et al. Mapping and role of T cell response in SARS-CoV-2-infected mice. J. Exp. Med. 218. https://doi.org/10.1084/jem.20202187 (2021).

  47. Hassert, M. et al. mRNA-induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2. PLoS Pathog. 16, e1009163 (2020).

    Google Scholar 

  48. van Bergen, J. et al. Multiantigen pan-sarbecovirus DNA vaccines generate protective T cell immune responses. JCI Insight 8. https://doi.org/10.1172/jci.insight.172488 (2023).

  49. Kingstad-Bakke, B. et al. Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants. Proc. Natl. Acad. Sci. USA 119, e2118312119 (2022).

    Google Scholar 

  50. Tarres-Freixas, F. et al. Heterogeneous infectivity and pathogenesis of SARS-CoV-2 variants Beta, Delta and Omicron in transgenic K18-hACE2 and wildtype mice. Front. Microbiol. 13, 840757 (2022).

    Google Scholar 

  51. Gary, E. N. et al. A novel mouse AAV6 hACE2 transduction model of wild-type SARS-CoV-2 infection studied using synDNA immunogens. iScience 24, 102699 (2021).

    Google Scholar 

  52. Rathnasinghe, R. et al. Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection. Emerg. Microbes Infect. 9, 2433–2445 (2020).

    Google Scholar 

  53. Tailor, N. et al. Generation and characterization of a SARS-CoV-2-susceptible mouse model using adeno-associated virus (AAV6.2FF)-mediated respiratory delivery of the human ACE2 gene. Viruses 15. https://doi.org/10.3390/v15010085 (2022).

  54. Glazkova, D. V. et al. Generation of SARS-CoV-2 mouse model by transient expression of the human ACE2 gene mediated by intranasal administration of AAV-hACE2. Mol. Biol. 56, 705–712 (2022).

    Google Scholar 

  55. Tran, B. M. et al. Air-liquid-interface differentiated human nose epithelium: a robust primary tissue culture model of SARS-CoV-2 infection. Int. J. Mol. Sci. 23, https://doi.org/10.3390/ijms23020835 (2022).

  56. Chen, Y. et al. Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses. Nat. Rev. Immunol. 23, 189–199 (2023).

    Google Scholar 

  57. Wu, W. L. et al. Monoclonal antibody targeting the conserved region of the SARS-CoV-2 spike protein to overcome viral variants. JCI Insight 7. https://doi.org/10.1172/jci.insight.157597 (2022).

  58. Wang, Z. et al. Analysis of memory B cells identifies conserved neutralizing epitopes on the N-terminal domain of variant SARS-CoV-2 spike proteins. Immunity 55, 998–1012 e1018 (2022).

    Google Scholar 

  59. Ng, K. W. et al. SARS-CoV-2 S2-targeted vaccination elicits broadly neutralizing antibodies. Sci. Transl. Med. 14, eabn3715 (2022).

    Google Scholar 

  60. Pinto, D. et al. Broad betacoronavirus neutralization by a stem helix-specific human antibody. Science 373, 1109–1116 (2021).

    Google Scholar 

  61. Dacon, C. et al. Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses. Cell Host Microbe 31, 97–111 e112 (2023).

    Google Scholar 

  62. Richardson, S. I. et al. SARS-CoV-2 Beta and Delta variants trigger FC effector function with increased cross-reactivity. Cell Rep. Med. 3, 100510 (2022).

    Google Scholar 

  63. Madhi, S. A. et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med 384, 1885–98 (2021).

    Google Scholar 

  64. Kustin, T. et al. Evidence for increased breakthrough rates of SARS-CoV-2 variants ofconcern in BNT162b2-mRNA-vaccinated individuals. Nat. Med. 27, 1379–1384 (2021).

    Google Scholar 

  65. Li, Q. et al. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell. https://doi.org/10.1016/j.cell.2020.07.012 (2020).

  66. Nguyen, T. H. O., et al. CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naïve precursor frequency and T cell receptor promiscuity. Immunity. https://doi.org/10.1016/j.immuni.2021.04.009 (2021).

  67. Wagner, K. I. et al. Recruitment of highly cytotoxic CD8(+) T cell receptors in mild SARS-CoV-2 infection. Cell Rep. 38, 110214 (2022).

    Google Scholar 

  68. Bertoletti, A., Le Bert, N. & Tan, A. T. SARS-CoV-2-specific T cells in the changing landscape of the COVID-19 pandemic. Immunity 55, 1764–1778 (2022).

    Google Scholar 

  69. Guo, L. et al. SARS-CoV-2-specific antibody and T-cell responses 1 year after infection in people recovered from COVID-19: a longitudinal cohort study. Lancet Microbe 3, e348–e356 (2022).

    Google Scholar 

  70. Rydyznski Moderbacher, C. et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell 183, 996–1012 e1019 (2020).

    Google Scholar 

  71. Schulz, A. R. et al. SARS-CoV-2 specific plasma cells acquire long-lived phenotypes in human bone marrow. EBioMedicine 95, 104735 (2023).

    Google Scholar 

  72. Nguyen, D. C. et al. COVID-19 and plasma cells: is there long-lived protection? Immunol. Rev. 309, 40–63 (2022).

    Google Scholar 

  73. Giannotta, G. & Giannotta, N. mRNA COVID-19 vaccines and long-lived plasma cells: a complicated relationship. Vaccines 9. https://doi.org/10.3390/vaccines9121503 (2021).

  74. Halliley, J. L. et al. Long-lived plasma cells are contained within the CD19(-)CD38(hi)CD138(+) subset in human bone marrow. Immunity 43, 132–145 (2015).

    Google Scholar 

  75. Turner, J. S. et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature 596, 109–113 (2021).

    Google Scholar 

  76. Kato, Y. et al. Multifaceted effects of antigen valency on B cell response composition and differentiation in vivo. Immunity 53, 548–563 e548 (2020).

    Google Scholar 

  77. Bhattacharya, D. Instructing durable humoral immunity for COVID-19 and other vaccinable diseases. Immunity 55, 945–964 (2022).

    Google Scholar 

  78. Cyster, J. G. & Allen, C. D. C. B Cell responses: cell interaction dynamics and decisions. Cell 177, 524–540 (2019).

    Google Scholar 

  79. Bennett, N. R., Zwick, D. B., Courtney, A. H. & Kiessling, L. L. Multivalent antigens for promoting B and T cell activation. ACS Chem. Biol. 10, 1817–1824 (2015).

    Google Scholar 

  80. Brooks, J. F. et al. Molecular basis for potent B cell responses to antigen displayed on particles of viral size. Nat. Immunol. 24, 1762–1777 (2023).

    Google Scholar 

  81. Ferapontov, A. et al. Antigen footprint governs activation of the B cell receptor. Nat. Commun. 14, 976 (2023).

    Google Scholar 

  82. Yao, H. et al. Molecular architecture of the SARS-CoV-2 virus. Cell 183, 730–738 e713 (2020).

    Google Scholar 

  83. Christiansen, D. et al. Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery. Sci. Rep. 9, 9251 (2019).

    Google Scholar 

  84. Cai, J. P. et al. Intranasal boosting with spike Fc-RBD of Wild-Type SARS-CoV-2 induces neutralizing antibodies against omicron subvariants and reduces viral load in the nasal turbinate of mice. Viruses 15. https://doi.org/10.3390/v15030687 (2023).

  85. Tabynov, K. et al. An intranasal vaccine comprising SARS-CoV-2 spike receptor-binding domain protein entrapped in mannose-conjugated chitosan nanoparticle provides protection in hamsters. Sci. Rep. 13, 12115 (2023).

    Google Scholar 

  86. Xing, M. et al. An intranasal combination vaccine induces systemic and mucosal immunity against COVID-19 and influenza. NPJ Vaccines 9, 64 (2024).

    Google Scholar 

  87. Earnest-Silveira, L. et al. Characterization of a hepatitis C virus-like particle vaccine produced in a human hepatocyte-derived cell line. J. Gen. Virol. 97, 1865–1876 (2016).

    Google Scholar 

  88. Deliyannis, G. et al. Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine. EBioMedicine 92, 104574 (2023).

    Google Scholar 

  89. Hierholzer, J. C. & Killington, R. A. Virus isolation and quantitation. Virology Methods Manual, 25–46 (Elsevier, 1996).

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Acknowledgements

This work was supported by grants from the National Health and Medical Research Council (NHMRC) Medical Research Future Fund (MRFF) (APP2013957), Avalia Immunotherapies Limited, Wellington, New Zealand, Vaccine Alliance Aotearoa New Zealand, Wellington, New Zealand; JT and DG acknowledge support from the Jack Ma Foundation for parts of the SARS-CoV-2 VLP work in this manuscript. SG is supported by an NHMRC Senior Research Fellowship (1159272). DIG was supported by an NHMRC Senior Research Fellowship (1117766) and subsequently by an NHMRC Investigator Grant (2008913). The salary for EV was supported by an NHMRC Ideas grant awarded to EV and JT (APP1181580). For W.R.H. by NHMRC 1154457, and for L.E.H. by NHMRC 2012701. LFW and CWT at Duke-NUS, supported by grants from Singapore National Medical Research Council (STPRG-FY19-001, COVID19RF-003 and OFLCG19-May-0034). D.F.J.P is supported by the MRFF mRNA Clinical Trial Enabling Infrastructure Grant MRFCTI000025 through the Department of Industry, Science Energy and Resources (DISER) “RNA Powered Antiviral Antibodies”. The authors would like to thank Rebecca Plavcak and Charley Mackenzie-Kludas for technical support for during the murine studies conducted at the Doherty Institute. We also thank Yaseelan Palarasah, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark, for providing anti-RBD monoclonal antibody, clone 20-14-5, for immunoprecipitation studies.

Author information

Author notes

  1. These authors contributed equally: Linda Earnest, Daniel Fernandez Ruiz, Melissa A. Edeling.

Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Parkville, Melbourne, VIC, Australia

    Linda Earnest, Daniel Fernandez Ruiz, Melissa A. Edeling, Julio Carrera Montoya, Ashley Huey Yiing Yap, Chinn Yi Wong, Lauren E. Holz, Simon Collett, Samantha L. Grimley, Damian F. J. Purcell, Dale I. Godfrey, Danielle E. Anderson, Kanta Subbarao, Jason M. Mackenzie, Steven Rockman, William R. Heath & Joseph Torresi

  2. School of Biomedical Sciences, Faculty of Medicine & Health and the UNSW RNA Institute, The University of New South Wales, Kensington, NSW, Australia

    Daniel Fernandez Ruiz

  3. Infection and Immunity Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, VIC, Australia

    Stephanie Gras

  4. Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, Australia

    Stephanie Gras

  5. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia

    Stephanie Gras

  6. Department of Paediatrics, University of Melbourne Parkville, Melbourne, VIC, Australia

    Simon Collett

  7. School of Science, College of Science, Engineering and Health, RMIT University, Melbourne, VIC, Australia

    Simon Collett

  8. Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia

    James P. Cooney, Kathryn C. Davidson & Marc Pellegrini

  9. Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia

    James P. Cooney, Kathryn C. Davidson & Marc Pellegrini

  10. Victorian Infectious Diseases Reference Laboratory, Doherty Institute for Infection and Immunity, Royal Melbourne Hospital, Melbourne, VIC, Australia

    Jason Roberts, Jamie Mumford, Elizabeth Vincan & Danielle E. Anderson

  11. Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore

    Chee Wah Tan & Lin-Fa Wang

  12. Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Chee Wah Tan & Lin-Fa Wang

  13. Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA

    Matthew Frieman

  14. Research, Innovation & Commercialisation, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Parkville, Victoria, Australia

    Dhiraj Hans

  15. Curtin Medical School, Curtin University, Perth, WA, Australia

    Elizabeth Vincan

  16. WHO Collaborating Centre for Reference and Research on Influenza, VIDRL at the Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia

    Kanta Subbarao

  17. Centenary Institute, The University of Sydney, Camperdown, NSW, Australia

    Marc Pellegrini

  18. Vaccine Innovation Unit, Seqirus/CSL, Parkville, VIC, Australia

    Steven Rockman

Authors

  1. Linda Earnest
  2. Daniel Fernandez Ruiz
  3. Melissa A. Edeling
  4. Julio Carrera Montoya
  5. Ashley Huey Yiing Yap
  6. Chinn Yi Wong
  7. Lauren E. Holz
  8. Stephanie Gras
  9. Simon Collett
  10. James P. Cooney
  11. Kathryn C. Davidson
  12. Samantha L. Grimley
  13. Damian F. J. Purcell
  14. Jason Roberts
  15. Jamie Mumford
  16. Chee Wah Tan
  17. Lin-Fa Wang
  18. Dale I. Godfrey
  19. Matthew Frieman
  20. Dhiraj Hans
  21. Elizabeth Vincan
  22. Danielle E. Anderson
  23. Kanta Subbarao
  24. Marc Pellegrini
  25. Jason M. Mackenzie
  26. Steven Rockman
  27. William R. Heath
  28. Joseph Torresi

Contributions

Investigation and formal data analysis: M.A.E., D.F.Z., L.E., J.C.M., A.H.Y.Y., C.Y.W., L.E.H., S.C., J.P.C., K.C.D., S.L.G., D.F.J.P., M.F., D.I.G., J.R., J.M., C.W.T., L.F.W., D.E.A., K.S., M.P., W.R.H., J.T. Resources: D.F.R., L.E,H., S.G., J.P.C., K.C.D., S.L.G., J.R., J.M., C.W.T., L.F.W., D.E.A., J.T. Project administration: C.Y.W., D.H., J.M.M., E.V., S.R., W.R.H., J.T. Conceptualisation: M.A.E., L.E., J.M.M., D.I.G., E.V., S.R., W.R.H., J.T. Supervision: M.A.E., L.E., K.S., M.P., J.M.M., E.V., S.R., W.R.H., J.T. Writing—original draft: M.A.E, D.F.R, J.T. Writing—reviewing and editing: All authors. Verification of data: M.A.E., D.F.R., L.E., J.C.M., K.C.D., J.R., C.W.T., L.F.W., M.F., D.E.A., J.T. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Joseph Torresi.

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Competing interests

Two patents (PCT/AU2022/050844 and PCT/AU2022/050843) covering the SARS-CoV-2 VLP vaccines and the underlying technology described in this study have been submitted through The University of Melbourne, with D.I.G. and J.T. as co-inventors. C.W.T. and L.-F.W. are co-inventors of a patent on the surrogate virus neutralization test (sVNT) platform. S.R. is an employee of CSL Seqirus. The authors declare no competing interests.

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Earnest, L., Ruiz, D.F., Edeling, M.A. et al. Preclinical development of a cross-protective β-SARS-CoV-2 virus-like particle vaccine adjuvanted with MF59. npj Vaccines (2026). https://doi.org/10.1038/s41541-025-01355-y

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