Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2
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,...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Daniel Watterson [verfasserIn] Danushka K Wijesundara [verfasserIn] Naphak Modhiran [verfasserIn] Francesca L Mordant [verfasserIn] Zheyi Li [verfasserIn] Michael S Avumegah [verfasserIn] Christopher LD McMillan [verfasserIn] Julia Lackenby [verfasserIn] Kate Guilfoyle [verfasserIn] Geert vanAmerongen [verfasserIn] Koert Stittelaar [verfasserIn] Stacey TM Cheung [verfasserIn] Summa Bibby [verfasserIn] Mallory Daleris [verfasserIn] Kym Hoger [verfasserIn] Marianne Gillard [verfasserIn] Eve Radunz [verfasserIn] Martina L Jones [verfasserIn] Karen Hughes [verfasserIn] Ben Hughes [verfasserIn] Justin Goh [verfasserIn] David Edwards [verfasserIn] Judith Scoble [verfasserIn] Lesley Pearce [verfasserIn] Lukasz Kowalczyk [verfasserIn] Tram Phan [verfasserIn] Mylinh La [verfasserIn] Louis Lu [verfasserIn] Tam Pham [verfasserIn] Qi Zhou [verfasserIn] David A Brockman [verfasserIn] Sherry J Morgan [verfasserIn] Cora Lau [verfasserIn] Mai H Tran [verfasserIn] Peter Tapley [verfasserIn] Fernando Villalón‐Letelier [verfasserIn] James Barnes [verfasserIn] Andrew Young [verfasserIn] Noushin Jaberolansar [verfasserIn] Connor AP Scott [verfasserIn] Ariel Isaacs [verfasserIn] Alberto A Amarilla [verfasserIn] Alexander A Khromykh [verfasserIn] Judith MA van denBrand [verfasserIn] Patrick C Reading [verfasserIn] Charani Ranasinghe [verfasserIn] Kanta Subbarao [verfasserIn] Trent P Munro [verfasserIn] Paul R Young [verfasserIn] Keith J Chappell [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021 |
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| Übergeordnetes Werk: |
In: Clinical & Translational Immunology - Wiley, 2015, 10(2021), 4, Seite n/a-n/a |
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| Übergeordnetes Werk: |
volume:10 ; year:2021 ; number:4 ; pages:n/a-n/a |
| Links: |
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| DOI / URN: |
10.1002/cti2.1269 |
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| Katalog-ID: |
DOAJ058708855 |
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| 245 | 1 | 0 | |a Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2 |
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| 520 | |a 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. | ||
| 650 | 4 | |a Molecular Clamp | |
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| 650 | 4 | |a rapid response | |
| 650 | 4 | |a SARS‐CoV‐2 | |
| 650 | 4 | |a subunit vaccine | |
| 653 | 0 | |a Immunologic diseases. Allergy | |
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| 700 | 0 | |a Naphak Modhiran |e verfasserin |4 aut | |
| 700 | 0 | |a Francesca L Mordant |e verfasserin |4 aut | |
| 700 | 0 | |a Zheyi Li |e verfasserin |4 aut | |
| 700 | 0 | |a Michael S Avumegah |e verfasserin |4 aut | |
| 700 | 0 | |a Christopher LD McMillan |e verfasserin |4 aut | |
| 700 | 0 | |a Julia Lackenby |e verfasserin |4 aut | |
| 700 | 0 | |a Kate Guilfoyle |e verfasserin |4 aut | |
| 700 | 0 | |a Geert vanAmerongen |e verfasserin |4 aut | |
| 700 | 0 | |a Koert Stittelaar |e verfasserin |4 aut | |
| 700 | 0 | |a Stacey TM Cheung |e verfasserin |4 aut | |
| 700 | 0 | |a Summa Bibby |e verfasserin |4 aut | |
| 700 | 0 | |a Mallory Daleris |e verfasserin |4 aut | |
| 700 | 0 | |a Kym Hoger |e verfasserin |4 aut | |
| 700 | 0 | |a Marianne Gillard |e verfasserin |4 aut | |
| 700 | 0 | |a Eve Radunz |e verfasserin |4 aut | |
| 700 | 0 | |a Martina L Jones |e verfasserin |4 aut | |
| 700 | 0 | |a Karen Hughes |e verfasserin |4 aut | |
| 700 | 0 | |a Ben Hughes |e verfasserin |4 aut | |
| 700 | 0 | |a Justin Goh |e verfasserin |4 aut | |
| 700 | 0 | |a David Edwards |e verfasserin |4 aut | |
| 700 | 0 | |a Judith Scoble |e verfasserin |4 aut | |
| 700 | 0 | |a Lesley Pearce |e verfasserin |4 aut | |
| 700 | 0 | |a Lukasz Kowalczyk |e verfasserin |4 aut | |
| 700 | 0 | |a Tram Phan |e verfasserin |4 aut | |
| 700 | 0 | |a Mylinh La |e verfasserin |4 aut | |
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| 700 | 0 | |a Cora Lau |e verfasserin |4 aut | |
| 700 | 0 | |a Mai H Tran |e verfasserin |4 aut | |
| 700 | 0 | |a Peter Tapley |e verfasserin |4 aut | |
| 700 | 0 | |a Fernando Villalón‐Letelier |e verfasserin |4 aut | |
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| 700 | 0 | |a Andrew Young |e verfasserin |4 aut | |
| 700 | 0 | |a Noushin Jaberolansar |e verfasserin |4 aut | |
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| 700 | 0 | |a Alexander A Khromykh |e verfasserin |4 aut | |
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| 700 | 0 | |a Charani Ranasinghe |e verfasserin |4 aut | |
| 700 | 0 | |a Kanta Subbarao |e verfasserin |4 aut | |
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| 700 | 0 | |a Paul R Young |e verfasserin |4 aut | |
| 700 | 0 | |a Keith J Chappell |e verfasserin |4 aut | |
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10.1002/cti2.1269 doi (DE-627)DOAJ058708855 (DE-599)DOAJ75b08e009f4c4222be30bd2650f67488 DE-627 ger DE-627 rakwb eng RC581-607 Daniel Watterson verfasserin aut Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Molecular Clamp neutralising antibodies polyfunctional T cells rapid response SARS‐CoV‐2 subunit vaccine Immunologic diseases. Allergy Danushka K Wijesundara verfasserin aut Naphak Modhiran verfasserin aut Francesca L Mordant verfasserin aut Zheyi Li verfasserin aut Michael S Avumegah verfasserin aut Christopher LD McMillan verfasserin aut Julia Lackenby verfasserin aut Kate Guilfoyle verfasserin aut Geert vanAmerongen verfasserin aut Koert Stittelaar verfasserin aut Stacey TM Cheung verfasserin aut Summa Bibby verfasserin aut Mallory Daleris verfasserin aut Kym Hoger verfasserin aut Marianne Gillard verfasserin aut Eve Radunz verfasserin aut Martina L Jones verfasserin aut Karen Hughes verfasserin aut Ben Hughes verfasserin aut Justin Goh verfasserin aut David Edwards verfasserin aut Judith Scoble verfasserin aut Lesley Pearce verfasserin aut Lukasz Kowalczyk verfasserin aut Tram Phan verfasserin aut Mylinh La verfasserin aut Louis Lu verfasserin aut Tam Pham verfasserin aut Qi Zhou verfasserin aut David A Brockman verfasserin aut Sherry J Morgan verfasserin aut Cora Lau verfasserin aut Mai H Tran verfasserin aut Peter Tapley verfasserin aut Fernando Villalón‐Letelier verfasserin aut James Barnes verfasserin aut Andrew Young verfasserin aut Noushin Jaberolansar verfasserin aut Connor AP Scott verfasserin aut Ariel Isaacs verfasserin aut Alberto A Amarilla verfasserin aut Alexander A Khromykh verfasserin aut Judith MA van denBrand verfasserin aut Patrick C Reading verfasserin aut Charani Ranasinghe verfasserin aut Kanta Subbarao verfasserin aut Trent P Munro verfasserin aut Paul R Young verfasserin aut Keith J Chappell verfasserin aut In Clinical & Translational Immunology Wiley, 2015 10(2021), 4, Seite n/a-n/a (DE-627)731890310 (DE-600)2694482-0 20500068 nnns volume:10 year:2021 number:4 pages:n/a-n/a https://doi.org/10.1002/cti2.1269 kostenfrei https://doaj.org/article/75b08e009f4c4222be30bd2650f67488 kostenfrei https://doi.org/10.1002/cti2.1269 kostenfrei https://doaj.org/toc/2050-0068 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 4 n/a-n/a |
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10.1002/cti2.1269 doi (DE-627)DOAJ058708855 (DE-599)DOAJ75b08e009f4c4222be30bd2650f67488 DE-627 ger DE-627 rakwb eng RC581-607 Daniel Watterson verfasserin aut Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Molecular Clamp neutralising antibodies polyfunctional T cells rapid response SARS‐CoV‐2 subunit vaccine Immunologic diseases. Allergy Danushka K Wijesundara verfasserin aut Naphak Modhiran verfasserin aut Francesca L Mordant verfasserin aut Zheyi Li verfasserin aut Michael S Avumegah verfasserin aut Christopher LD McMillan verfasserin aut Julia Lackenby verfasserin aut Kate Guilfoyle verfasserin aut Geert vanAmerongen verfasserin aut Koert Stittelaar verfasserin aut Stacey TM Cheung verfasserin aut Summa Bibby verfasserin aut Mallory Daleris verfasserin aut Kym Hoger verfasserin aut Marianne Gillard verfasserin aut Eve Radunz verfasserin aut Martina L Jones verfasserin aut Karen Hughes verfasserin aut Ben Hughes verfasserin aut Justin Goh verfasserin aut David Edwards verfasserin aut Judith Scoble verfasserin aut Lesley Pearce verfasserin aut Lukasz Kowalczyk verfasserin aut Tram Phan verfasserin aut Mylinh La verfasserin aut Louis Lu verfasserin aut Tam Pham verfasserin aut Qi Zhou verfasserin aut David A Brockman verfasserin aut Sherry J Morgan verfasserin aut Cora Lau verfasserin aut Mai H Tran verfasserin aut Peter Tapley verfasserin aut Fernando Villalón‐Letelier verfasserin aut James Barnes verfasserin aut Andrew Young verfasserin aut Noushin Jaberolansar verfasserin aut Connor AP Scott verfasserin aut Ariel Isaacs verfasserin aut Alberto A Amarilla verfasserin aut Alexander A Khromykh verfasserin aut Judith MA van denBrand verfasserin aut Patrick C Reading verfasserin aut Charani Ranasinghe verfasserin aut Kanta Subbarao verfasserin aut Trent P Munro verfasserin aut Paul R Young verfasserin aut Keith J Chappell verfasserin aut In Clinical & Translational Immunology Wiley, 2015 10(2021), 4, Seite n/a-n/a (DE-627)731890310 (DE-600)2694482-0 20500068 nnns volume:10 year:2021 number:4 pages:n/a-n/a https://doi.org/10.1002/cti2.1269 kostenfrei https://doaj.org/article/75b08e009f4c4222be30bd2650f67488 kostenfrei https://doi.org/10.1002/cti2.1269 kostenfrei https://doaj.org/toc/2050-0068 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 4 n/a-n/a |
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10.1002/cti2.1269 doi (DE-627)DOAJ058708855 (DE-599)DOAJ75b08e009f4c4222be30bd2650f67488 DE-627 ger DE-627 rakwb eng RC581-607 Daniel Watterson verfasserin aut Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Molecular Clamp neutralising antibodies polyfunctional T cells rapid response SARS‐CoV‐2 subunit vaccine Immunologic diseases. Allergy Danushka K Wijesundara verfasserin aut Naphak Modhiran verfasserin aut Francesca L Mordant verfasserin aut Zheyi Li verfasserin aut Michael S Avumegah verfasserin aut Christopher LD McMillan verfasserin aut Julia Lackenby verfasserin aut Kate Guilfoyle verfasserin aut Geert vanAmerongen verfasserin aut Koert Stittelaar verfasserin aut Stacey TM Cheung verfasserin aut Summa Bibby verfasserin aut Mallory Daleris verfasserin aut Kym Hoger verfasserin aut Marianne Gillard verfasserin aut Eve Radunz verfasserin aut Martina L Jones verfasserin aut Karen Hughes verfasserin aut Ben Hughes verfasserin aut Justin Goh verfasserin aut David Edwards verfasserin aut Judith Scoble verfasserin aut Lesley Pearce verfasserin aut Lukasz Kowalczyk verfasserin aut Tram Phan verfasserin aut Mylinh La verfasserin aut Louis Lu verfasserin aut Tam Pham verfasserin aut Qi Zhou verfasserin aut David A Brockman verfasserin aut Sherry J Morgan verfasserin aut Cora Lau verfasserin aut Mai H Tran verfasserin aut Peter Tapley verfasserin aut Fernando Villalón‐Letelier verfasserin aut James Barnes verfasserin aut Andrew Young verfasserin aut Noushin Jaberolansar verfasserin aut Connor AP Scott verfasserin aut Ariel Isaacs verfasserin aut Alberto A Amarilla verfasserin aut Alexander A Khromykh verfasserin aut Judith MA van denBrand verfasserin aut Patrick C Reading verfasserin aut Charani Ranasinghe verfasserin aut Kanta Subbarao verfasserin aut Trent P Munro verfasserin aut Paul R Young verfasserin aut Keith J Chappell verfasserin aut In Clinical & Translational Immunology Wiley, 2015 10(2021), 4, Seite n/a-n/a (DE-627)731890310 (DE-600)2694482-0 20500068 nnns volume:10 year:2021 number:4 pages:n/a-n/a https://doi.org/10.1002/cti2.1269 kostenfrei https://doaj.org/article/75b08e009f4c4222be30bd2650f67488 kostenfrei https://doi.org/10.1002/cti2.1269 kostenfrei https://doaj.org/toc/2050-0068 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 4 n/a-n/a |
| allfieldsGer |
10.1002/cti2.1269 doi (DE-627)DOAJ058708855 (DE-599)DOAJ75b08e009f4c4222be30bd2650f67488 DE-627 ger DE-627 rakwb eng RC581-607 Daniel Watterson verfasserin aut Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Molecular Clamp neutralising antibodies polyfunctional T cells rapid response SARS‐CoV‐2 subunit vaccine Immunologic diseases. Allergy Danushka K Wijesundara verfasserin aut Naphak Modhiran verfasserin aut Francesca L Mordant verfasserin aut Zheyi Li verfasserin aut Michael S Avumegah verfasserin aut Christopher LD McMillan verfasserin aut Julia Lackenby verfasserin aut Kate Guilfoyle verfasserin aut Geert vanAmerongen verfasserin aut Koert Stittelaar verfasserin aut Stacey TM Cheung verfasserin aut Summa Bibby verfasserin aut Mallory Daleris verfasserin aut Kym Hoger verfasserin aut Marianne Gillard verfasserin aut Eve Radunz verfasserin aut Martina L Jones verfasserin aut Karen Hughes verfasserin aut Ben Hughes verfasserin aut Justin Goh verfasserin aut David Edwards verfasserin aut Judith Scoble verfasserin aut Lesley Pearce verfasserin aut Lukasz Kowalczyk verfasserin aut Tram Phan verfasserin aut Mylinh La verfasserin aut Louis Lu verfasserin aut Tam Pham verfasserin aut Qi Zhou verfasserin aut David A Brockman verfasserin aut Sherry J Morgan verfasserin aut Cora Lau verfasserin aut Mai H Tran verfasserin aut Peter Tapley verfasserin aut Fernando Villalón‐Letelier verfasserin aut James Barnes verfasserin aut Andrew Young verfasserin aut Noushin Jaberolansar verfasserin aut Connor AP Scott verfasserin aut Ariel Isaacs verfasserin aut Alberto A Amarilla verfasserin aut Alexander A Khromykh verfasserin aut Judith MA van denBrand verfasserin aut Patrick C Reading verfasserin aut Charani Ranasinghe verfasserin aut Kanta Subbarao verfasserin aut Trent P Munro verfasserin aut Paul R Young verfasserin aut Keith J Chappell verfasserin aut In Clinical & Translational Immunology Wiley, 2015 10(2021), 4, Seite n/a-n/a (DE-627)731890310 (DE-600)2694482-0 20500068 nnns volume:10 year:2021 number:4 pages:n/a-n/a https://doi.org/10.1002/cti2.1269 kostenfrei https://doaj.org/article/75b08e009f4c4222be30bd2650f67488 kostenfrei https://doi.org/10.1002/cti2.1269 kostenfrei https://doaj.org/toc/2050-0068 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 4 n/a-n/a |
| allfieldsSound |
10.1002/cti2.1269 doi (DE-627)DOAJ058708855 (DE-599)DOAJ75b08e009f4c4222be30bd2650f67488 DE-627 ger DE-627 rakwb eng RC581-607 Daniel Watterson verfasserin aut Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Molecular Clamp neutralising antibodies polyfunctional T cells rapid response SARS‐CoV‐2 subunit vaccine Immunologic diseases. Allergy Danushka K Wijesundara verfasserin aut Naphak Modhiran verfasserin aut Francesca L Mordant verfasserin aut Zheyi Li verfasserin aut Michael S Avumegah verfasserin aut Christopher LD McMillan verfasserin aut Julia Lackenby verfasserin aut Kate Guilfoyle verfasserin aut Geert vanAmerongen verfasserin aut Koert Stittelaar verfasserin aut Stacey TM Cheung verfasserin aut Summa Bibby verfasserin aut Mallory Daleris verfasserin aut Kym Hoger verfasserin aut Marianne Gillard verfasserin aut Eve Radunz verfasserin aut Martina L Jones verfasserin aut Karen Hughes verfasserin aut Ben Hughes verfasserin aut Justin Goh verfasserin aut David Edwards verfasserin aut Judith Scoble verfasserin aut Lesley Pearce verfasserin aut Lukasz Kowalczyk verfasserin aut Tram Phan verfasserin aut Mylinh La verfasserin aut Louis Lu verfasserin aut Tam Pham verfasserin aut Qi Zhou verfasserin aut David A Brockman verfasserin aut Sherry J Morgan verfasserin aut Cora Lau verfasserin aut Mai H Tran verfasserin aut Peter Tapley verfasserin aut Fernando Villalón‐Letelier verfasserin aut James Barnes verfasserin aut Andrew Young verfasserin aut Noushin Jaberolansar verfasserin aut Connor AP Scott verfasserin aut Ariel Isaacs verfasserin aut Alberto A Amarilla verfasserin aut Alexander A Khromykh verfasserin aut Judith MA van denBrand verfasserin aut Patrick C Reading verfasserin aut Charani Ranasinghe verfasserin aut Kanta Subbarao verfasserin aut Trent P Munro verfasserin aut Paul R Young verfasserin aut Keith J Chappell verfasserin aut In Clinical & Translational Immunology Wiley, 2015 10(2021), 4, Seite n/a-n/a (DE-627)731890310 (DE-600)2694482-0 20500068 nnns volume:10 year:2021 number:4 pages:n/a-n/a https://doi.org/10.1002/cti2.1269 kostenfrei https://doaj.org/article/75b08e009f4c4222be30bd2650f67488 kostenfrei https://doi.org/10.1002/cti2.1269 kostenfrei https://doaj.org/toc/2050-0068 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 4 n/a-n/a |
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In Clinical & Translational Immunology 10(2021), 4, Seite n/a-n/a volume:10 year:2021 number:4 pages:n/a-n/a |
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Molecular Clamp neutralising antibodies polyfunctional T cells rapid response SARS‐CoV‐2 subunit vaccine Immunologic diseases. Allergy |
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Daniel Watterson @@aut@@ Danushka K Wijesundara @@aut@@ Naphak Modhiran @@aut@@ Francesca L Mordant @@aut@@ Zheyi Li @@aut@@ Michael S Avumegah @@aut@@ Christopher LD McMillan @@aut@@ Julia Lackenby @@aut@@ Kate Guilfoyle @@aut@@ Geert vanAmerongen @@aut@@ Koert Stittelaar @@aut@@ Stacey TM Cheung @@aut@@ Summa Bibby @@aut@@ Mallory Daleris @@aut@@ Kym Hoger @@aut@@ Marianne Gillard @@aut@@ Eve Radunz @@aut@@ Martina L Jones @@aut@@ Karen Hughes @@aut@@ Ben Hughes @@aut@@ Justin Goh @@aut@@ David Edwards @@aut@@ Judith Scoble @@aut@@ Lesley Pearce @@aut@@ Lukasz Kowalczyk @@aut@@ Tram Phan @@aut@@ Mylinh La @@aut@@ Louis Lu @@aut@@ Tam Pham @@aut@@ Qi Zhou @@aut@@ David A Brockman @@aut@@ Sherry J Morgan @@aut@@ Cora Lau @@aut@@ Mai H Tran @@aut@@ Peter Tapley @@aut@@ Fernando Villalón‐Letelier @@aut@@ James Barnes @@aut@@ Andrew Young @@aut@@ Noushin Jaberolansar @@aut@@ Connor AP Scott @@aut@@ Ariel Isaacs @@aut@@ Alberto A Amarilla @@aut@@ Alexander A Khromykh @@aut@@ Judith MA van denBrand @@aut@@ Patrick C Reading @@aut@@ Charani Ranasinghe @@aut@@ Kanta Subbarao @@aut@@ Trent P Munro @@aut@@ Paul R Young @@aut@@ Keith J Chappell @@aut@@ |
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englisch |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ058708855</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230308225838.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2021 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1002/cti2.1269</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ058708855</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ75b08e009f4c4222be30bd2650f67488</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Daniel Watterson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Molecular Clamp</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">neutralising antibodies</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">polyfunctional T cells</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">rapid response</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">SARS‐CoV‐2</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">subunit vaccine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. 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Daniel Watterson Danushka K Wijesundara Naphak Modhiran Francesca L Mordant Zheyi Li Michael S Avumegah Christopher LD McMillan Julia Lackenby Kate Guilfoyle Geert vanAmerongen Koert Stittelaar Stacey TM Cheung Summa Bibby Mallory Daleris Kym Hoger Marianne Gillard Eve Radunz Martina L Jones Karen Hughes Ben Hughes Justin Goh David Edwards Judith Scoble Lesley Pearce Lukasz Kowalczyk Tram Phan Mylinh La Louis Lu Tam Pham Qi Zhou David A Brockman Sherry J Morgan Cora Lau Mai H Tran Peter Tapley Fernando Villalón‐Letelier James Barnes Andrew Young Noushin Jaberolansar Connor AP Scott Ariel Isaacs Alberto A Amarilla Alexander A Khromykh Judith MA van denBrand Patrick C Reading Charani Ranasinghe Kanta Subbarao Trent P Munro Paul R Young Keith J Chappell |
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preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2 |
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Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2 |
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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. |
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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. |
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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. |
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