dc.contributor.author |
Singh, Advaita Acarya
|
|
dc.contributor.author |
Pooe, Ofentse
|
|
dc.contributor.author |
Kwezi, Lusisizwe
|
|
dc.contributor.author |
Lotter-Stark, Therese
|
|
dc.contributor.author |
Stoychev, Stoyan H.
|
|
dc.contributor.author |
Alexandra, Kabamba
|
|
dc.contributor.author |
Gerber, Isak
|
|
dc.contributor.author |
Bhiman, Jinal N.
|
|
dc.contributor.author |
Vorster, Juan
|
|
dc.contributor.author |
Pauly, Michael
|
|
dc.contributor.author |
Zeitlin, Larry
|
|
dc.contributor.author |
Whaley, Kevin
|
|
dc.contributor.author |
Mach, Lukas
|
|
dc.contributor.author |
Steinkellner, Herta
|
|
dc.contributor.author |
Morris, Lynn
|
|
dc.contributor.author |
Tsekoa, Tsepo Lebiletsa
|
|
dc.contributor.author |
Chikwamba, Rachel
|
|
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 |