tetano
Editor, Senior Moderator
Clin Transl Immunology
. 2021 Apr 5;10(4):e1269.
doi: 10.1002/cti2.1269. eCollection 2021.
Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2
Daniel Watterson[SUP] 1 2 3 [/SUP], Danushka K Wijesundara[SUP] 1 2 [/SUP], Naphak Modhiran[SUP] 1 2 [/SUP], Francesca L Mordant[SUP] 4 [/SUP], Zheyi Li[SUP] 5 [/SUP], Michael S Avumegah[SUP] 1 2 [/SUP], Christopher Ld McMillan[SUP] 1 2 [/SUP], Julia Lackenby[SUP] 1 2 [/SUP], Kate Guilfoyle[SUP] 6 [/SUP], Geert van Amerongen[SUP] 6 [/SUP], Koert Stittelaar[SUP] 6 [/SUP], Stacey Tm Cheung[SUP] 1 [/SUP], Summa Bibby[SUP] 1 [/SUP], Mallory Daleris[SUP] 2 [/SUP], Kym Hoger[SUP] 2 [/SUP], Marianne Gillard[SUP] 2 [/SUP], Eve Radunz[SUP] 2 [/SUP], Martina L Jones[SUP] 2 [/SUP], Karen Hughes[SUP] 2 [/SUP], Ben Hughes[SUP] 2 [/SUP], Justin Goh[SUP] 2 [/SUP], David Edwards[SUP] 2 [/SUP], Judith Scoble[SUP] 7 [/SUP], Lesley Pearce[SUP] 7 [/SUP], Lukasz Kowalczyk[SUP] 7 [/SUP], Tram Phan[SUP] 7 [/SUP], Mylinh La[SUP] 7 [/SUP], Louis Lu[SUP] 7 [/SUP], Tam Pham[SUP] 7 [/SUP], Qi Zhou[SUP] 7 [/SUP], David A Brockman[SUP] 8 [/SUP], Sherry J Morgan[SUP] 9 [/SUP], Cora Lau[SUP] 10 [/SUP], Mai H Tran[SUP] 8 [/SUP], Peter Tapley[SUP] 8 [/SUP], Fernando Villal?n-Letelier[SUP] 4 [/SUP], James Barnes[SUP] 11 [/SUP], Andrew Young[SUP] 1 2 [/SUP], Noushin Jaberolansar[SUP] 1 2 [/SUP], Connor Ap Scott[SUP] 1 [/SUP], Ariel Isaacs[SUP] 1 [/SUP], Alberto A Amarilla[SUP] 1 [/SUP], Alexander A Khromykh[SUP] 1 3 [/SUP], Judith Ma van den Brand[SUP] 12 [/SUP], Patrick C Reading[SUP] 4 11 [/SUP], Charani Ranasinghe[SUP] 5 [/SUP], Kanta Subbarao[SUP] 4 11 [/SUP], Trent P Munro[SUP] 1 2 [/SUP], Paul R Young[SUP] 1 2 3 [/SUP], Keith J Chappell[SUP] 1 2 3 [/SUP]
Affiliations
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[SUP]+[/SUP] and cytotoxic CD8[SUP]+[/SUP] 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: Molecular Clamp; SARS?CoV?2; neutralising antibodies; polyfunctional T cells; rapid response; subunit vaccine.
. 2021 Apr 5;10(4):e1269.
doi: 10.1002/cti2.1269. eCollection 2021.
Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2
Daniel Watterson[SUP] 1 2 3 [/SUP], Danushka K Wijesundara[SUP] 1 2 [/SUP], Naphak Modhiran[SUP] 1 2 [/SUP], Francesca L Mordant[SUP] 4 [/SUP], Zheyi Li[SUP] 5 [/SUP], Michael S Avumegah[SUP] 1 2 [/SUP], Christopher Ld McMillan[SUP] 1 2 [/SUP], Julia Lackenby[SUP] 1 2 [/SUP], Kate Guilfoyle[SUP] 6 [/SUP], Geert van Amerongen[SUP] 6 [/SUP], Koert Stittelaar[SUP] 6 [/SUP], Stacey Tm Cheung[SUP] 1 [/SUP], Summa Bibby[SUP] 1 [/SUP], Mallory Daleris[SUP] 2 [/SUP], Kym Hoger[SUP] 2 [/SUP], Marianne Gillard[SUP] 2 [/SUP], Eve Radunz[SUP] 2 [/SUP], Martina L Jones[SUP] 2 [/SUP], Karen Hughes[SUP] 2 [/SUP], Ben Hughes[SUP] 2 [/SUP], Justin Goh[SUP] 2 [/SUP], David Edwards[SUP] 2 [/SUP], Judith Scoble[SUP] 7 [/SUP], Lesley Pearce[SUP] 7 [/SUP], Lukasz Kowalczyk[SUP] 7 [/SUP], Tram Phan[SUP] 7 [/SUP], Mylinh La[SUP] 7 [/SUP], Louis Lu[SUP] 7 [/SUP], Tam Pham[SUP] 7 [/SUP], Qi Zhou[SUP] 7 [/SUP], David A Brockman[SUP] 8 [/SUP], Sherry J Morgan[SUP] 9 [/SUP], Cora Lau[SUP] 10 [/SUP], Mai H Tran[SUP] 8 [/SUP], Peter Tapley[SUP] 8 [/SUP], Fernando Villal?n-Letelier[SUP] 4 [/SUP], James Barnes[SUP] 11 [/SUP], Andrew Young[SUP] 1 2 [/SUP], Noushin Jaberolansar[SUP] 1 2 [/SUP], Connor Ap Scott[SUP] 1 [/SUP], Ariel Isaacs[SUP] 1 [/SUP], Alberto A Amarilla[SUP] 1 [/SUP], Alexander A Khromykh[SUP] 1 3 [/SUP], Judith Ma van den Brand[SUP] 12 [/SUP], Patrick C Reading[SUP] 4 11 [/SUP], Charani Ranasinghe[SUP] 5 [/SUP], Kanta Subbarao[SUP] 4 11 [/SUP], Trent P Munro[SUP] 1 2 [/SUP], Paul R Young[SUP] 1 2 3 [/SUP], Keith J Chappell[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 33841880
- PMCID: PMC8021130
- DOI: 10.1002/cti2.1269
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[SUP]+[/SUP] and cytotoxic CD8[SUP]+[/SUP] 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: Molecular Clamp; SARS?CoV?2; neutralising antibodies; polyfunctional T cells; rapid response; subunit vaccine.