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Characterization of VRC01, a potent and broadly neutralizing anti‐HIV mAb, produced in transiently and stably transformed tobacco

The proposed clinical trial in Africa of VRC01, a potent broadly neutralizing antibody (bNAb) capable of neutralizing 91% of known HIV‐1 isolates, raises concerns about testing a treatment which will be too expensive to be accessible by the most important target population, the poor in under‐develop...

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Detalles Bibliográficos
Autores principales: Teh, Audrey Y‐H., Maresch, Daniel, Klein, Katja, Ma, Julian K‐C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Pub 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112721/
https://www.ncbi.nlm.nih.gov/pubmed/24256218
http://dx.doi.org/10.1111/pbi.12137
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author Teh, Audrey Y‐H.
Maresch, Daniel
Klein, Katja
Ma, Julian K‐C.
author_facet Teh, Audrey Y‐H.
Maresch, Daniel
Klein, Katja
Ma, Julian K‐C.
author_sort Teh, Audrey Y‐H.
collection PubMed
description The proposed clinical trial in Africa of VRC01, a potent broadly neutralizing antibody (bNAb) capable of neutralizing 91% of known HIV‐1 isolates, raises concerns about testing a treatment which will be too expensive to be accessible by the most important target population, the poor in under‐developed regions such as sub‐Saharan Africa. Here, we report the expression of VRC01 in plants as an economic alternative to conventional mammalian‐cell‐based production platforms. The heavy and light chain genes of VRC01 were cloned onto a single vector, pTRAk.2, which was transformed into Nicotiana benthamiana or Nicotiana tabacum using transient and stable expression production systems respectively. VRC01 has been successfully expressed transiently in plants with expression level of approximately 80 mg antibody/kg; stable transgenic lines expressing up to 100 mg antibody/kg were also obtained. Plant‐produced VRC01 from both systems showed a largely homogeneous N‐glycosylation profile with a single dominant glycoform. The binding kinetics to gp120 IIIB (approximately 1 nm), neutralization of HIV‐1 BaL or a panel of 10 VRC01‐sensitive HIV‐1 Env pseudoviruses of VRC01 produced in transient and stable plants were also consistent with VRC01 from HEK cells.
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spelling pubmed-41127212014-08-27 Characterization of VRC01, a potent and broadly neutralizing anti‐HIV mAb, produced in transiently and stably transformed tobacco Teh, Audrey Y‐H. Maresch, Daniel Klein, Katja Ma, Julian K‐C. Plant Biotechnol J Research Articles The proposed clinical trial in Africa of VRC01, a potent broadly neutralizing antibody (bNAb) capable of neutralizing 91% of known HIV‐1 isolates, raises concerns about testing a treatment which will be too expensive to be accessible by the most important target population, the poor in under‐developed regions such as sub‐Saharan Africa. Here, we report the expression of VRC01 in plants as an economic alternative to conventional mammalian‐cell‐based production platforms. The heavy and light chain genes of VRC01 were cloned onto a single vector, pTRAk.2, which was transformed into Nicotiana benthamiana or Nicotiana tabacum using transient and stable expression production systems respectively. VRC01 has been successfully expressed transiently in plants with expression level of approximately 80 mg antibody/kg; stable transgenic lines expressing up to 100 mg antibody/kg were also obtained. Plant‐produced VRC01 from both systems showed a largely homogeneous N‐glycosylation profile with a single dominant glycoform. The binding kinetics to gp120 IIIB (approximately 1 nm), neutralization of HIV‐1 BaL or a panel of 10 VRC01‐sensitive HIV‐1 Env pseudoviruses of VRC01 produced in transient and stable plants were also consistent with VRC01 from HEK cells. Blackwell Pub 2013-11-21 2014-03-20 /pmc/articles/PMC4112721/ /pubmed/24256218 http://dx.doi.org/10.1111/pbi.12137 Text en © 2013 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology, The Association of Applied Biologists and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/3.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Teh, Audrey Y‐H.
Maresch, Daniel
Klein, Katja
Ma, Julian K‐C.
Characterization of VRC01, a potent and broadly neutralizing anti‐HIV mAb, produced in transiently and stably transformed tobacco
title Characterization of VRC01, a potent and broadly neutralizing anti‐HIV mAb, produced in transiently and stably transformed tobacco
title_full Characterization of VRC01, a potent and broadly neutralizing anti‐HIV mAb, produced in transiently and stably transformed tobacco
title_fullStr Characterization of VRC01, a potent and broadly neutralizing anti‐HIV mAb, produced in transiently and stably transformed tobacco
title_full_unstemmed Characterization of VRC01, a potent and broadly neutralizing anti‐HIV mAb, produced in transiently and stably transformed tobacco
title_short Characterization of VRC01, a potent and broadly neutralizing anti‐HIV mAb, produced in transiently and stably transformed tobacco
title_sort characterization of vrc01, a potent and broadly neutralizing anti‐hiv mab, produced in transiently and stably transformed tobacco
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112721/
https://www.ncbi.nlm.nih.gov/pubmed/24256218
http://dx.doi.org/10.1111/pbi.12137
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