A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV)
dc.contributor.author | Shen, Yen-Ju | en_ZA |
dc.contributor.author | Shephard, Enid | en_ZA |
dc.contributor.author | Douglass, Nicola | en_ZA |
dc.contributor.author | Johnston, Nicolette | en_ZA |
dc.contributor.author | Adams, Craig | en_ZA |
dc.contributor.author | Williamson, Carolyn | en_ZA |
dc.contributor.author | Williamson, Anna-Lise | en_ZA |
dc.date.accessioned | 2015-11-18T03:58:52Z | |
dc.date.available | 2015-11-18T03:58:52Z | |
dc.date.issued | 2011 | en_ZA |
dc.description.abstract | BACKGROUND: The Capripoxvirus, Lumpy skin disease virus (LSDV) has a restricted host-range and is being investigated as a novel HIV-1 vaccine vector. LSDV does not complete its replication cycle in non-ruminant hosts. METHODS: The safety of LSDV was tested at doses of 104 and 106 plaque forming units in two strains of immunocompromised mice, namely RAG mice and CD4 T cell knockout mice. LSDV expressing HIV-1 subtype C Gag, reverse transcriptase (RT), Tat and Nef as a polyprotein (Grttn), (rLSDV-grttn), was constructed. The immunogenicity of rLSDV-grttn was tested in homologous prime-boost regimens as well as heterologous prime-boost regimes in combination with a DNA vaccine (pVRC-grttn) or modified vaccinia Ankara vaccine (rMVA-grttn) both expressing Grttn. RESULTS: Safety was demonstrated in two strains of immunocompromised mice.In the immunogenicity experiments mice developed high magnitudes of HIV-specific cells producing IFN-gamma and IL-2. A comparison of rLSDV-grttn and rMVA-grttn to boost a DNA vaccine (pVRC-grttn) indicated a DNA prime and rLSDV-grttn boost induced a 2 fold (p < 0.01) lower cumulative frequency of Gag- and RT-specific IFN-gamma CD8 and CD4 cells than a boost with rMVA-grttn. However, the HIV-specific cells induced by the DNA vaccine prime rLSDV-grttn boost produced greater than 3 fold (p < 0.01) more IFN- gamma than the HIV-specific cells induced by the DNA vaccine prime rMVA-grttn boost. A boost of HIV-specific CD4 cells producing IL-2 was only achieved with the DNA vaccine prime and rLSDV-grttn boost. Heterologous prime-boost combinations of rLSDV-grttn and rMVA-grttn induced similar cumulative frequencies of IFN- gamma producing Gag- and RT-specific CD8 and CD4 cells. A significant difference (p < 0.01) between the regimens was the higher capacity (2.1 fold) of Gag-and RT-specific CD4 cells to produce IFN-gamma with a rMVA-grttn prime - rLSDV-grttn boost. This regimen also induced a 1.5 fold higher (p < 0.05) frequency of Gag- and RT-specific CD4 cells producing IL-2. CONCLUSIONS: LSDV was demonstrated to be non-pathogenic in immunocompromised mice. The rLSDV-grttn vaccine was immunogenic in mice particularly in prime-boost regimens. The data suggests that this novel vaccine may be useful for enhancing, in particular, HIV-specific CD4 IFN- gamma and IL-2 responses induced by a priming vaccine. | en_ZA |
dc.identifier.apacitation | Shen, Y., Shephard, E., Douglass, N., Johnston, N., Adams, C., Williamson, C., & Williamson, A. (2011). A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV). <i>Virology Journal</i>, http://hdl.handle.net/11427/15087 | en_ZA |
dc.identifier.chicagocitation | Shen, Yen-Ju, Enid Shephard, Nicola Douglass, Nicolette Johnston, Craig Adams, Carolyn Williamson, and Anna-Lise Williamson "A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV)." <i>Virology Journal</i> (2011) http://hdl.handle.net/11427/15087 | en_ZA |
dc.identifier.citation | Shen, Y. J., Shephard, E., Douglass, N., Johnston, N., Adams, C., Williamson, C., & Williamson, A. L. (2011). A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV). Virol J, 8, 265. | en_ZA |
dc.identifier.ris | TY - Journal Article AU - Shen, Yen-Ju AU - Shephard, Enid AU - Douglass, Nicola AU - Johnston, Nicolette AU - Adams, Craig AU - Williamson, Carolyn AU - Williamson, Anna-Lise AB - BACKGROUND: The Capripoxvirus, Lumpy skin disease virus (LSDV) has a restricted host-range and is being investigated as a novel HIV-1 vaccine vector. LSDV does not complete its replication cycle in non-ruminant hosts. METHODS: The safety of LSDV was tested at doses of 104 and 106 plaque forming units in two strains of immunocompromised mice, namely RAG mice and CD4 T cell knockout mice. LSDV expressing HIV-1 subtype C Gag, reverse transcriptase (RT), Tat and Nef as a polyprotein (Grttn), (rLSDV-grttn), was constructed. The immunogenicity of rLSDV-grttn was tested in homologous prime-boost regimens as well as heterologous prime-boost regimes in combination with a DNA vaccine (pVRC-grttn) or modified vaccinia Ankara vaccine (rMVA-grttn) both expressing Grttn. RESULTS: Safety was demonstrated in two strains of immunocompromised mice.In the immunogenicity experiments mice developed high magnitudes of HIV-specific cells producing IFN-gamma and IL-2. A comparison of rLSDV-grttn and rMVA-grttn to boost a DNA vaccine (pVRC-grttn) indicated a DNA prime and rLSDV-grttn boost induced a 2 fold (p < 0.01) lower cumulative frequency of Gag- and RT-specific IFN-gamma CD8 and CD4 cells than a boost with rMVA-grttn. However, the HIV-specific cells induced by the DNA vaccine prime rLSDV-grttn boost produced greater than 3 fold (p < 0.01) more IFN- gamma than the HIV-specific cells induced by the DNA vaccine prime rMVA-grttn boost. A boost of HIV-specific CD4 cells producing IL-2 was only achieved with the DNA vaccine prime and rLSDV-grttn boost. Heterologous prime-boost combinations of rLSDV-grttn and rMVA-grttn induced similar cumulative frequencies of IFN- gamma producing Gag- and RT-specific CD8 and CD4 cells. A significant difference (p < 0.01) between the regimens was the higher capacity (2.1 fold) of Gag-and RT-specific CD4 cells to produce IFN-gamma with a rMVA-grttn prime - rLSDV-grttn boost. This regimen also induced a 1.5 fold higher (p < 0.05) frequency of Gag- and RT-specific CD4 cells producing IL-2. CONCLUSIONS: LSDV was demonstrated to be non-pathogenic in immunocompromised mice. The rLSDV-grttn vaccine was immunogenic in mice particularly in prime-boost regimens. The data suggests that this novel vaccine may be useful for enhancing, in particular, HIV-specific CD4 IFN- gamma and IL-2 responses induced by a priming vaccine. DA - 2011 DB - OpenUCT DO - 10.1186/1743-422X-8-265 DP - University of Cape Town J1 - Virology Journal LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV) TI - A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV) UR - http://hdl.handle.net/11427/15087 ER - | en_ZA |
dc.identifier.uri | http://hdl.handle.net/11427/15087 | |
dc.identifier.uri | http://dx.doi.org/10.1186/1743-422X-8-265 | |
dc.identifier.vancouvercitation | Shen Y, Shephard E, Douglass N, Johnston N, Adams C, Williamson C, et al. A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV). Virology Journal. 2011; http://hdl.handle.net/11427/15087. | en_ZA |
dc.language.iso | eng | en_ZA |
dc.publisher | BioMed Central Ltd | en_ZA |
dc.publisher.department | Institute of Infectious Disease and Molecular Medicine | en_ZA |
dc.publisher.faculty | Faculty of Health Sciences | en_ZA |
dc.publisher.institution | University of Cape Town | |
dc.rights | This is an Open Access article distributed under the terms of the Creative Commons Attribution License | en_ZA |
dc.rights.holder | 2011 Shen et al; licensee BioMed Central Ltd. | en_ZA |
dc.rights.uri | http://creativecommons.org/licenses/by/2.0 | en_ZA |
dc.source | Virology Journal | en_ZA |
dc.source.uri | http://www.virologyj.com/ | en_ZA |
dc.subject.other | Capripoxvirus | en_ZA |
dc.subject.other | Lumpy skin disease virus (LSDV) | en_ZA |
dc.subject.other | HIV/AIDS | en_ZA |
dc.title | A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV) | en_ZA |
dc.type | Journal Article | en_ZA |
uct.type.filetype | Text | |
uct.type.filetype | Image | |
uct.type.publication | Research | en_ZA |
uct.type.resource | Article | en_ZA |
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