Plant-based production of highly potent anti-HIV antibodies with engineered posttranslational modifications
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Date
Authors
Singh, Advaita Acarya
Pooe, Ofentse
Kwezi, Lusisizwe
Lotter-Stark, Therese
Stoychev, Stoyan H.
Alexandra, Kabamba
Gerber, Isak
Bhiman, Jinal N.
Vorster, Juan
Pauly, Michael
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group
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.
Description
Keywords
Prevention, Treatment, Antibody therapy, Recombinant vaccine, Broadly neutralising antibodies (bNAbs), Human immunodeficiency virus type 1 (HIV-1), Human immunodeficiency virus (HIV), Post-translational modification (PTM)
Sustainable Development Goals
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.