LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters
The SARS-CoV-2 pandemic demonstrated the need for potent and broad-spectrum vaccines. This study reports the development and testing of a lumpy skin disease virus (LSDV)-vectored vaccine against SARS-CoV-2, utilizing stabilized spike and conserved nucleocapsid proteins as antigens to develop robust...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/7/1409 |
| _version_ | 1797587229958209536 |
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| author | Warren R. J. de Moor Anna-Lise Williamson Georgia Schäfer Nicola Douglass Sophette Gers Andrew D. Sutherland Melissa J. Blumenthal Emmanuel Margolin Megan L. Shaw Wolfgang Preiser Rosamund Chapman |
| author_facet | Warren R. J. de Moor Anna-Lise Williamson Georgia Schäfer Nicola Douglass Sophette Gers Andrew D. Sutherland Melissa J. Blumenthal Emmanuel Margolin Megan L. Shaw Wolfgang Preiser Rosamund Chapman |
| author_sort | Warren R. J. de Moor |
| collection | DOAJ |
| description | The SARS-CoV-2 pandemic demonstrated the need for potent and broad-spectrum vaccines. This study reports the development and testing of a lumpy skin disease virus (LSDV)-vectored vaccine against SARS-CoV-2, utilizing stabilized spike and conserved nucleocapsid proteins as antigens to develop robust immunogenicity. Construction of the vaccine (LSDV-SARS2-S,N) was confirmed by polymerase chain reaction (PCR) amplification and sequencing. In vitro characterization confirmed that cells infected with LSDV-SARS2-S,N expressed SARS-CoV-2 spike and nucleocapsid protein. In BALB/c mice, the vaccine elicited high magnitude IFN-γ ELISpot responses (spike: 2808 SFU/10<sup>6</sup> splenocytes) and neutralizing antibodies (ID<sub>50</sub> = 6552). Testing in hamsters, which emulate human COVID-19 disease progression, showed the development of high titers of neutralizing antibodies against the Wuhan and Delta SARS-CoV-2 variants (Wuhan ID<sub>50</sub> = 2905; Delta ID<sub>50</sub> = 4648). Additionally, hamsters vaccinated with LSDV-SARS2-S,N displayed significantly less weight loss, lung damage, and reduced viral RNA copies following SARS-CoV-2 infection with the Delta variant as compared to controls, demonstrating protection against disease. These data demonstrate that LSDV-vectored vaccines display promise as an effective SARS-CoV-2 vaccine and as a potential vaccine platform for communicable diseases in humans and animals. Further efficacy testing and immune response analysis, particularly in non-human primates, are warranted. |
| first_indexed | 2024-03-11T00:34:09Z |
| format | Article |
| id | doaj.art-5e56cadf6d3f431fb18147f734cb9ea9 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T00:34:09Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-5e56cadf6d3f431fb18147f734cb9ea92023-11-18T21:43:17ZengMDPI AGViruses1999-49152023-06-01157140910.3390/v15071409LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in HamstersWarren R. J. de Moor0Anna-Lise Williamson1Georgia Schäfer2Nicola Douglass3Sophette Gers4Andrew D. Sutherland5Melissa J. Blumenthal6Emmanuel Margolin7Megan L. Shaw8Wolfgang Preiser9Rosamund Chapman10Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South AfricaDivision of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South AfricaDivision of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South AfricaPathcare VetLab, Cape Town 7463, South AfricaDivision of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University Tygerberg Campus, Cape Town 7505, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South AfricaDivision of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University Tygerberg Campus, Cape Town 7505, South AfricaDivision of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University Tygerberg Campus, Cape Town 7505, South AfricaDivision of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South AfricaThe SARS-CoV-2 pandemic demonstrated the need for potent and broad-spectrum vaccines. This study reports the development and testing of a lumpy skin disease virus (LSDV)-vectored vaccine against SARS-CoV-2, utilizing stabilized spike and conserved nucleocapsid proteins as antigens to develop robust immunogenicity. Construction of the vaccine (LSDV-SARS2-S,N) was confirmed by polymerase chain reaction (PCR) amplification and sequencing. In vitro characterization confirmed that cells infected with LSDV-SARS2-S,N expressed SARS-CoV-2 spike and nucleocapsid protein. In BALB/c mice, the vaccine elicited high magnitude IFN-γ ELISpot responses (spike: 2808 SFU/10<sup>6</sup> splenocytes) and neutralizing antibodies (ID<sub>50</sub> = 6552). Testing in hamsters, which emulate human COVID-19 disease progression, showed the development of high titers of neutralizing antibodies against the Wuhan and Delta SARS-CoV-2 variants (Wuhan ID<sub>50</sub> = 2905; Delta ID<sub>50</sub> = 4648). Additionally, hamsters vaccinated with LSDV-SARS2-S,N displayed significantly less weight loss, lung damage, and reduced viral RNA copies following SARS-CoV-2 infection with the Delta variant as compared to controls, demonstrating protection against disease. These data demonstrate that LSDV-vectored vaccines display promise as an effective SARS-CoV-2 vaccine and as a potential vaccine platform for communicable diseases in humans and animals. Further efficacy testing and immune response analysis, particularly in non-human primates, are warranted.https://www.mdpi.com/1999-4915/15/7/1409SARS-CoV-2LSDVCOVID-19vaccinechallengenucleocapsid |
| spellingShingle | Warren R. J. de Moor Anna-Lise Williamson Georgia Schäfer Nicola Douglass Sophette Gers Andrew D. Sutherland Melissa J. Blumenthal Emmanuel Margolin Megan L. Shaw Wolfgang Preiser Rosamund Chapman LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters Viruses SARS-CoV-2 LSDV COVID-19 vaccine challenge nucleocapsid |
| title | LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters |
| title_full | LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters |
| title_fullStr | LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters |
| title_full_unstemmed | LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters |
| title_short | LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters |
| title_sort | lsdv vectored sars cov 2 s and n vaccine protects against severe clinical disease in hamsters |
| topic | SARS-CoV-2 LSDV COVID-19 vaccine challenge nucleocapsid |
| url | https://www.mdpi.com/1999-4915/15/7/1409 |
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