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

被引:4
作者
de Moor, Warren R. J. [1 ,2 ]
Williamson, Anna-Lise [1 ,2 ]
Schafer, Georgia [2 ,3 ,4 ]
Douglass, Nicola [1 ,2 ]
Gers, Sophette [5 ]
Sutherland, Andrew D. [6 ]
Blumenthal, Melissa J. [2 ,3 ]
Margolin, Emmanuel [2 ,4 ,7 ]
Shaw, Megan L. [6 ,8 ]
Preiser, Wolfgang [6 ]
Chapman, Rosamund [1 ,2 ]
机构
[1] Univ Cape Town, Fac Hlth Sci, Dept Pathol, Div Med Virol, ZA-7925 Cape Town, South Africa
[2] Univ Cape Town, Inst Infect Dis & Mol Med, Fac Hlth Sci, ZA-7925 Cape Town, South Africa
[3] Int Ctr Genet Engn & Biotechnol, ZA-7925 Cape Town, South Africa
[4] Univ Cape Town, Wellcome Trust Ctr Infect Dis Res Africa, ZA-7925 Cape Town, South Africa
[5] Pathcare VetLab, ZA-7463 Cape Town, South Africa
[6] Stellenbosch Univ, Fac Med & Hlth Sci, Div Med Virol, Tygerberg Campus, ZA-7505 Cape Town, South Africa
[7] Univ Cape Town, Dept Mol & Cell Biol, Biopharming Res Unit, ZA-7701 Cape Town, South Africa
[8] Univ Western Cape, Fac Nat Sci, Dept Med Biosci, ZA-7535 Cape Town, South Africa
来源
VIRUSES-BASEL | 2023年 / 15卷 / 07期
关键词
SARS-CoV-2; LSDV; COVID-19; vaccine; challenge; nucleocapsid; spike; lumpy skin disease virus; poxvirus; CAPRIPOXVIRUS; VIRUS;
D O I
10.3390/v15071409
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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/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.
引用
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页数:17
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