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

Scientific reports 2020 Apr 10

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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.

Citation

Advaita Acarya Singh, Ofentse Pooe, Lusisizwe Kwezi, Therese Lotter-Stark, Stoyan H Stoychev, Kabamba Alexandra, Isak Gerber, Jinal N Bhiman, Juan Vorster, Michael Pauly, Larry Zeitlin, Kevin Whaley, Lukas Mach, Herta Steinkellner, Lynn Morris, Tsepo Lebiletsa Tsekoa, Rachel Chikwamba. Plant-based production of highly potent anti-HIV antibodies with engineered posttranslational modifications. Scientific reports. 2020 Apr 10;10(1):6201