Setting up a platform for plant-based influenza virus vaccine production in South Africa

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dc.contributor.authorMortimer, Elizabethen_ZA
dc.contributor.authorMaclean, Jamesen_ZA
dc.contributor.authorMbewana, Sandiswaen_ZA
dc.contributor.authorBuys, Ameliaen_ZA
dc.contributor.authorWilliamson, Anna-Liseen_ZA
dc.contributor.authorHitzeroth, Ingaen_ZA
dc.contributor.authorRybicki, Edwarden_ZA
dc.date.accessioned2015-10-30T09:32:08Z
dc.date.available2015-10-30T09:32:08Z
dc.date.issued2012en_ZA
dc.description.abstractBACKGROUND:During a global influenza pandemic, the vaccine requirements of developing countries can surpass their supply capabilities, if these exist at all, compelling them to rely on developed countries for stocks that may not be available in time. There is thus a need for developing countries in general to produce their own pandemic and possibly seasonal influenza vaccines. Here we describe the development of a plant-based platform for producing influenza vaccines locally, in South Africa. Plant-produced influenza vaccine candidates are quicker to develop and potentially cheaper than egg-produced influenza vaccines, and their production can be rapidly upscaled. In this study, we investigated the feasibility of producing a vaccine to the highly pathogenic avian influenza A subtype H5N1 virus, the most generally virulent influenza virus identified to date. Two variants of the haemagglutinin (HA) surface glycoprotein gene were synthesised for optimum expression in plants: these were the full-length HA gene (H5) and a truncated form lacking the transmembrane domain (H5tr). The genes were cloned into a panel of Agrobacterium tumefaciens binary plant expression vectors in order to test HA accumulation in different cell compartments. The constructs were transiently expressed in tobacco by means of agroinfiltration. Stable transgenic tobacco plants were also generated to provide seed for stable storage of the material as a pre-pandemic strategy. RESULTS: For both transient and transgenic expression systems the highest accumulation of full-length H5 protein occurred in the apoplastic spaces, while the highest accumulation of H5tr was in the endoplasmic reticulum. The H5 proteins were produced at relatively high concentrations in both systems. Following partial purification, haemagglutination and haemagglutination inhibition tests indicated that the conformation of the plant-produced HA variants was correct and the proteins were functional. The immunisation of chickens and mice with the candidate vaccines elicited HA-specific antibody responses. CONCLUSIONS: We managed, after synthesis of two versions of a single gene, to produce by transient and transgenic expression in plants, two variants of a highly pathogenic avian influenza virus HA protein which could have vaccine potential. This is a proof of principle of the potential of plant-produced influenza vaccines as a feasible pandemic response strategy for South Africa and other developing countries.en_ZA
dc.identifier.apacitationMortimer, E., Maclean, J., Mbewana, S., Buys, A., Williamson, A., Hitzeroth, I., & Rybicki, E. (2012). Setting up a platform for plant-based influenza virus vaccine production in South Africa. <i>BMC Biotechnology</i>, http://hdl.handle.net/11427/14519en_ZA
dc.identifier.chicagocitationMortimer, Elizabeth, James Maclean, Sandiswa Mbewana, Amelia Buys, Anna-Lise Williamson, Inga Hitzeroth, and Edward Rybicki "Setting up a platform for plant-based influenza virus vaccine production in South Africa." <i>BMC Biotechnology</i> (2012) http://hdl.handle.net/11427/14519en_ZA
dc.identifier.citationMortimer, E., Maclean, J. M., Mbewana, S., Buys, A., Williamson, A. L., Hitzeroth, I. I., & Rybicki, E. P. (2012). Setting up a platform for plant-based influenza virus vaccine production in South Africa. BMC biotechnology, 12(1), 14.en_ZA
dc.identifier.ris TY - Journal Article AU - Mortimer, Elizabeth AU - Maclean, James AU - Mbewana, Sandiswa AU - Buys, Amelia AU - Williamson, Anna-Lise AU - Hitzeroth, Inga AU - Rybicki, Edward AB - BACKGROUND:During a global influenza pandemic, the vaccine requirements of developing countries can surpass their supply capabilities, if these exist at all, compelling them to rely on developed countries for stocks that may not be available in time. There is thus a need for developing countries in general to produce their own pandemic and possibly seasonal influenza vaccines. Here we describe the development of a plant-based platform for producing influenza vaccines locally, in South Africa. Plant-produced influenza vaccine candidates are quicker to develop and potentially cheaper than egg-produced influenza vaccines, and their production can be rapidly upscaled. In this study, we investigated the feasibility of producing a vaccine to the highly pathogenic avian influenza A subtype H5N1 virus, the most generally virulent influenza virus identified to date. Two variants of the haemagglutinin (HA) surface glycoprotein gene were synthesised for optimum expression in plants: these were the full-length HA gene (H5) and a truncated form lacking the transmembrane domain (H5tr). The genes were cloned into a panel of Agrobacterium tumefaciens binary plant expression vectors in order to test HA accumulation in different cell compartments. The constructs were transiently expressed in tobacco by means of agroinfiltration. Stable transgenic tobacco plants were also generated to provide seed for stable storage of the material as a pre-pandemic strategy. RESULTS: For both transient and transgenic expression systems the highest accumulation of full-length H5 protein occurred in the apoplastic spaces, while the highest accumulation of H5tr was in the endoplasmic reticulum. The H5 proteins were produced at relatively high concentrations in both systems. Following partial purification, haemagglutination and haemagglutination inhibition tests indicated that the conformation of the plant-produced HA variants was correct and the proteins were functional. The immunisation of chickens and mice with the candidate vaccines elicited HA-specific antibody responses. CONCLUSIONS: We managed, after synthesis of two versions of a single gene, to produce by transient and transgenic expression in plants, two variants of a highly pathogenic avian influenza virus HA protein which could have vaccine potential. This is a proof of principle of the potential of plant-produced influenza vaccines as a feasible pandemic response strategy for South Africa and other developing countries. DA - 2012 DB - OpenUCT DO - 10.1186/1472-6750-12-14 DP - University of Cape Town J1 - BMC Biotechnology LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Setting up a platform for plant-based influenza virus vaccine production in South Africa TI - Setting up a platform for plant-based influenza virus vaccine production in South Africa UR - http://hdl.handle.net/11427/14519 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14519
dc.identifier.urihttp://dx.doi.org/10.1186/1472-6750-12-14
dc.identifier.vancouvercitationMortimer E, Maclean J, Mbewana S, Buys A, Williamson A, Hitzeroth I, et al. Setting up a platform for plant-based influenza virus vaccine production in South Africa. BMC Biotechnology. 2012; http://hdl.handle.net/11427/14519.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDepartment of Molecular and Cell Biologyen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2012 Mortimer et al.; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Biotechnologyen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcbiotechnol/en_ZA
dc.subject.otherAntibodies, Viralen_ZA
dc.subject.otherInfluenza Vaccinesen_ZA
dc.titleSetting up a platform for plant-based influenza virus vaccine production in South Africaen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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