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Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2.
Watterson, Daniel; Wijesundara, Danushka K; Modhiran, Naphak; Mordant, Francesca L; Li, Zheyi; Avumegah, Michael S; McMillan, Christopher Ld; Lackenby, Julia; Guilfoyle, Kate; van Amerongen, Geert; Stittelaar, Koert; Cheung, Stacey Tm; Bibby, Summa; Daleris, Mallory; Hoger, Kym; Gillard, Marianne; Radunz, Eve; Jones, Martina L; Hughes, Karen; Hughes, Ben; Goh, Justin; Edwards, David; Scoble, Judith; Pearce, Lesley; Kowalczyk, Lukasz; Phan, Tram; La, Mylinh; Lu, Louis; Pham, Tam; Zhou, Qi; Brockman, David A; Morgan, Sherry J; Lau, Cora; Tran, Mai H; Tapley, Peter; Villalón-Letelier, Fernando; Barnes, James; Young, Andrew; Jaberolansar, Noushin; Scott, Connor Ap; Isaacs, Ariel; Amarilla, Alberto A; Khromykh, Alexander A; van den Brand, Judith Ma; Reading, Patrick C; Ranasinghe, Charani; Subbarao, Kanta; Munro, Trent P; Young, Paul R; Chappell, Keith J.
  • Watterson D; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • Wijesundara DK; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Modhiran N; Australian Infectious Disease Research Centre, Global Virus Network Centre of Excellence The University of Queensland Brisbane QLD Australia.
  • Mordant FL; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • Li Z; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Avumegah MS; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • McMillan CL; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Lackenby J; Department of Microbiology and Immunology The University of Melbourne Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Guilfoyle K; Department of Immunology and Infectious Disease The John Curtin School of Medical Research, The Australian National University Canberra ACT Australia.
  • van Amerongen G; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • Stittelaar K; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Cheung ST; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • Bibby S; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Daleris M; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • Hoger K; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Gillard M; Viroclinics Xplore Schaijk The Netherlands.
  • Radunz E; Viroclinics Xplore Schaijk The Netherlands.
  • Jones ML; Viroclinics Xplore Schaijk The Netherlands.
  • Hughes K; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • Hughes B; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • Goh J; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Edwards D; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Scoble J; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Pearce L; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Kowalczyk L; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Phan T; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • La M; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Lu L; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Pham T; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Zhou Q; CSIRO Manufacturing Parkville VIC Australia.
  • Brockman DA; CSIRO Manufacturing Parkville VIC Australia.
  • Morgan SJ; CSIRO Manufacturing Parkville VIC Australia.
  • Lau C; CSIRO Manufacturing Parkville VIC Australia.
  • Tran MH; CSIRO Manufacturing Parkville VIC Australia.
  • Tapley P; CSIRO Manufacturing Parkville VIC Australia.
  • Villalón-Letelier F; CSIRO Manufacturing Parkville VIC Australia.
  • Barnes J; CSIRO Manufacturing Parkville VIC Australia.
  • Young A; TetraQ The University of Queensland St Lucia QLD Australia.
  • Jaberolansar N; StageBio Mason OH USA.
  • Scott CA; University of Queensland Biological Resources The University of Queensland St Lucia QLD Australia.
  • Isaacs A; TetraQ The University of Queensland St Lucia QLD Australia.
  • Amarilla AA; TetraQ The University of Queensland St Lucia QLD Australia.
  • Khromykh AA; Department of Microbiology and Immunology The University of Melbourne Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • van den Brand JM; WHO Collaborating Centre for Reference and Research on Influenza Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
  • Reading PC; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • Ranasinghe C; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Subbarao K; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • Munro TP; The Australian Institute for Bioengineering and Nanotechnology The University of Queensland St Lucia QLD Australia.
  • Young PR; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
  • Chappell KJ; School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.
Clin Transl Immunology ; 10(4): e1269, 2021.
Article in English | MEDLINE | ID: covidwho-1162553
ABSTRACT

OBJECTIVES:

Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia).

METHODS:

A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat.

RESULTS:

In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level.

CONCLUSION:

The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2-8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal: Clin Transl Immunology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal: Clin Transl Immunology Year: 2021 Document Type: Article