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

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

doi:10.3390/v15071409

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

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

Research output: Contribution to journal › Article › peer-review

Abstract

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/10⁶ splenocytes) and neutralizing antibodies (ID₅₀ = 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 ID₅₀ = 2905; Delta ID₅₀ = 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.

Original language	English
Article number	1409
Journal	Viruses
Volume	15
Issue number	7
DOIs	https://doi.org/10.3390/v15071409
State	Published - Jul 2023
Externally published	Yes

Keywords

COVID-19
LSDV
SARS-CoV-2
challenge
lumpy skin disease virus
nucleocapsid
poxvirus
spike
vaccine

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10.3390/v15071409

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@article{f0eab5e78c9549058bba6af31765f7fe,

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

abstract = "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/106 splenocytes) and neutralizing antibodies (ID50 = 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 ID50 = 2905; Delta ID50 = 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.",

keywords = "COVID-19, LSDV, SARS-CoV-2, challenge, lumpy skin disease virus, nucleocapsid, poxvirus, spike, vaccine",

author = "{de Moor}, {Warren R.J.} and Williamson, {Anna Lise} and Georgia Sch{\"a}fer and Nicola Douglass and Sophette Gers and Sutherland, {Andrew D.} and Blumenthal, {Melissa J.} and Emmanuel Margolin and Shaw, {Megan L.} and Wolfgang Preiser and Rosamund Chapman",

note = "Funding Information: The hamster challenge experiments were funded by the UCT Innovation Builder Fund (Project #IB20-14). Further supplementary funding was provided by the South African Research Chairs Initiative of the Department of Science and Technology and the National Research Foundation (grant number: 64815). G.S. is supported by the EDCTP2 program (Training and Mobility Action TMA2018SF-2446) and receives funding from the NRF, the MRC, and the PRF. SARS-CoV-2 isolation and propagation were partially supported by the South African Medical Research Council with funds received from the Department of Science and Innovation (M.L.S. and W.P.) and by the Poliomyelitis Research Foundation (WP, grant 21/81). A.D.S. was supported by a bursary from the Poliomyelitis Research Foundation (grant 21/45). M.J.B. holds an ACSR Young Investigator Pilot Award and has received funding from the NRF and the Oppenheimer Memorial Trust. Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = jul,

doi = "10.3390/v15071409",

language = "English",

volume = "15",

journal = "Viruses",

issn = "1999-4915",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "7",

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T1 - LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters

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

N1 - Funding Information: The hamster challenge experiments were funded by the UCT Innovation Builder Fund (Project #IB20-14). Further supplementary funding was provided by the South African Research Chairs Initiative of the Department of Science and Technology and the National Research Foundation (grant number: 64815). G.S. is supported by the EDCTP2 program (Training and Mobility Action TMA2018SF-2446) and receives funding from the NRF, the MRC, and the PRF. SARS-CoV-2 isolation and propagation were partially supported by the South African Medical Research Council with funds received from the Department of Science and Innovation (M.L.S. and W.P.) and by the Poliomyelitis Research Foundation (WP, grant 21/81). A.D.S. was supported by a bursary from the Poliomyelitis Research Foundation (grant 21/45). M.J.B. holds an ACSR Young Investigator Pilot Award and has received funding from the NRF and the Oppenheimer Memorial Trust. Publisher Copyright: © 2023 by the authors.

PY - 2023/7

Y1 - 2023/7

N2 - 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/106 splenocytes) and neutralizing antibodies (ID50 = 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 ID50 = 2905; Delta ID50 = 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.

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-γ ELISpot responses (spike: 2808 SFU/106 splenocytes) and neutralizing antibodies (ID50 = 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 ID50 = 2905; Delta ID50 = 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.

KW - COVID-19

KW - LSDV

KW - SARS-CoV-2

KW - challenge

KW - lumpy skin disease virus

KW - nucleocapsid

KW - poxvirus

KW - spike

KW - vaccine

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SN - 1999-4915

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JO - Viruses

JF - Viruses

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M1 - 1409

ER -

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

Abstract

Keywords

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