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dc.contributor.author | Singh, Advaita Acarya![]() |
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dc.contributor.author | Pooe, Ofentse![]() |
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dc.contributor.author | Kwezi, Lusisizwe![]() |
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dc.contributor.author | Lotter-Stark, Therese![]() |
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dc.contributor.author | Stoychev, Stoyan H.![]() |
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dc.contributor.author | Alexandra, Kabamba![]() |
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dc.contributor.author | Gerber, Isak![]() |
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dc.contributor.author | Bhiman, Jinal N.![]() |
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dc.contributor.author | Vorster, Juan![]() |
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dc.contributor.author | Pauly, Michael![]() |
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dc.contributor.author | Zeitlin, Larry![]() |
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dc.contributor.author | Whaley, Kevin![]() |
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dc.contributor.author | Mach, Lukas![]() |
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dc.contributor.author | Steinkellner, Herta![]() |
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dc.contributor.author | Morris, Lynn![]() |
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dc.contributor.author | Tsekoa, Tsepo Lebiletsa![]() |
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dc.contributor.author | Chikwamba, Rachel![]() |
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dc.date.accessioned | 2021-04-08T12:38:59Z | |
dc.date.available | 2021-04-08T12:38:59Z | |
dc.date.issued | 2020-04-10 | |
dc.description.abstract | Broadly neutralising antibodies (bNAbs) against human immunodeficiency virus type 1 (HIV-1), such as CAP256-VRC26 are being developed for HIV prevention and treatment. These Abs carry a unique but crucial post-translational modification (PTM), namely O-sulfated tyrosine in the heavy chain complementarity determining region (CDR) H3 loop. Several studies have demonstrated that plants are suitable hosts for the generation of highly active anti-HIV-1 antibodies with the potential to engineer PTMs. Here we report the expression and characterisation of CAP256-VRC26 bNAbs with posttranslational modifications (PTM). Two variants, CAP256-VRC26 (08 and 09) were expressed in glycoengineered Nicotiana benthamiana plants. By in planta co-expression of tyrosyl protein sulfotransferase 1, we installed O-sulfated tyrosine in CDR H3 of both bNAbs. These exhibited similar structural folding to the mammalian cell produced bNAbs, but non-sulfated versions showed loss of neutralisation breadth and potency. In contrast, tyrosine sulfated versions displayed equivalent neutralising activity to mammalian produced antibodies retaining exceptional potency against some subtype C viruses. Together, the data demonstrate the enormous potential of plant-based systems for multiple posttranslational engineering and production of fully active bNAbs for application in passive immunisation or as an alternative for current HIV/AIDS antiretroviral therapy regimens. | en_ZA |
dc.description.department | Plant Production and Soil Science | en_ZA |
dc.description.department | Production Animal Studies | en_ZA |
dc.description.librarian | am2021 | en_ZA |
dc.description.sponsorship | The Department of Science and Technology (DST), South African Medical Research Council - Strategic Health Innovation Partnership (SAMRC SHIP) and Council for Scientific and Industrial Research (CSIR). | en_ZA |
dc.description.uri | http://www.nature.com/srep | en_ZA |
dc.identifier.citation | Singh, A.A., Pooe, O., Kwezi, L. et al. Plant-based production of highly potent anti-HIV antibodies with engineered posttranslational modifications. Scientific Reports 10, 6201 (2020). https://doi.org/10.1038/s41598-020-63052-1. | en_ZA |
dc.identifier.issn | 2045-2322 (online) | |
dc.identifier.other | 10.1038/s41598-020-63052-1 | |
dc.identifier.uri | http://hdl.handle.net/2263/79366 | |
dc.language.iso | en | en_ZA |
dc.publisher | Nature Publishing Group | en_ZA |
dc.rights | © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License. | en_ZA |
dc.subject | Prevention | en_ZA |
dc.subject | Treatment | en_ZA |
dc.subject | Antibody therapy | en_ZA |
dc.subject | Recombinant vaccine | en_ZA |
dc.subject | Broadly neutralising antibodies (bNAbs) | en_ZA |
dc.subject | Human immunodeficiency virus type 1 (HIV-1) | en_ZA |
dc.subject | Human immunodeficiency virus (HIV) | en_ZA |
dc.subject | Post-translational modification (PTM) | en_ZA |
dc.title | Plant-based production of highly potent anti-HIV antibodies with engineered posttranslational modifications | en_ZA |
dc.type | Article | en_ZA |