LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters

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dc.contributor.authorde Moor, Warren R. J.
dc.contributor.authorWilliamson, Anna-Lise
dc.contributor.authorSchäfer, Georgia
dc.contributor.authorDouglass, Nicola
dc.contributor.authorGers, Sophette
dc.contributor.authorSutherland, Andrew D.
dc.contributor.authorBlumenthal, Melissa J.
dc.contributor.authorMargolin, Emmanuel
dc.contributor.authorShaw, Megan L.
dc.contributor.authorPreiser, Wolfgang
dc.contributor.authorChapman, Rosamund
dc.date.accessioned2023-08-11T06:50:34Z
dc.date.available2023-08-11T06:50:34Z
dc.date.issued2023-06-21
dc.date.updated2023-07-28T12:21:36Z
dc.description.abstractThe 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-&gamma; 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.en_US
dc.identifierdoi: 10.3390/v15071409
dc.identifier.apacitationde Moor, Warren R. J., Williamson, A., Schäfer, G., Douglass, N., Gers, S., Sutherland, Andrew D., ... Chapman, R. (2023). LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters. <i>Viruses</i>, 15(7), 1409. http://hdl.handle.net/11427/38222en_ZA
dc.identifier.chicagocitationde Moor, Warren R. J., Anna-Lise Williamson, Georgia Schäfer, Nicola Douglass, Sophette Gers, Andrew D. Sutherland, Melissa J. Blumenthal, et al "LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters." <i>Viruses</i> 15, 7. (2023): 1409. http://hdl.handle.net/11427/38222en_ZA
dc.identifier.citationde Moor, Warren R. J., Williamson, A., Schäfer, G., Douglass, N., Gers, S., Sutherland, Andrew D., Blumenthal, Melissa J. & Margolin, E. et al. 2023. LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters. <i>Viruses.</i> 15(7):1409. http://hdl.handle.net/11427/38222en_ZA
dc.identifier.risTY - Journal Article AU - de Moor, Warren R. J. AU - Williamson, Anna-Lise AU - Schäfer, Georgia AU - Douglass, Nicola AU - Gers, Sophette AU - Sutherland, Andrew D. AU - Blumenthal, Melissa J. AU - Margolin, Emmanuel AU - Shaw, Megan L. AU - Preiser, Wolfgang AU - Chapman, Rosamund AB - 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-&gamma; 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. DA - 2023-06-21 DB - OpenUCT DP - University of Cape Town IS - 7 J1 - Viruses KW - SARS-CoV-2 KW - LSDV KW - COVID-19 KW - vaccine KW - challenge KW - nucleocapsid KW - spike KW - lumpy skin KW - disease virus KW - poxvirus LK - https://open.uct.ac.za PY - 2023 T1 - LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters TI - LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters UR - http://hdl.handle.net/11427/38222 ER -en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/38222
dc.identifier.vancouvercitationde Moor Warren R J, Williamson A, Schäfer G, Douglass N, Gers S, Sutherland Andrew D, et al. LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters. Viruses. 2023;15(7):1409. http://hdl.handle.net/11427/38222.en_ZA
dc.publisher.departmentDepartment of Pathologyen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceVirusesen_US
dc.source.journalissue7en_US
dc.source.journalvolume15en_US
dc.source.pagination1409en_US
dc.source.urihttps://www.mdpi.com/journal/viruses
dc.subjectSARS-CoV-2en_US
dc.subjectLSDVen_US
dc.subjectCOVID-19
dc.subjectvaccine
dc.subjectchallenge
dc.subjectnucleocapsid
dc.subjectspike
dc.subjectlumpy skin
dc.subjectdisease virus
dc.subjectpoxvirus
dc.titleLSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamstersen_US
dc.typeJournal Articleen_US
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