Plant-based production of highly potent anti-HIV antibodies with engineered posttranslational modifications

Show simple item record Singh, Advaita Acarya Pooe, Ofentse Kwezi, Lusisizwe Lotter-Stark, Therese Stoychev, Stoyan H. Alexandra, Kabamba Gerber, Isak Bhiman, Jinal N. Vorster, Juan Pauly, Michael Zeitlin, Larry Whaley, Kevin Mach, Lukas Steinkellner, Herta Morris, Lynn Tsekoa, Tsepo Lebiletsa Chikwamba, Rachel 2021-04-08T12:38:59Z 2021-04-08T12:38:59Z 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 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). en_ZA
dc.identifier.issn 2045-2322 (online)
dc.identifier.other 10.1038/s41598-020-63052-1
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

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