Characterization of VRC 01, a potent and broadly neutralizing anti‐ HIV m A b, produced in transiently and stably transformed tobacco

Summary The proposed clinical trial in A frica of VRC 01, a potent broadly neutralizing antibody (b NA b) 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...

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Published in:Plant biotechnology journal 2014-04, Vol.12 (3), p.300-311
Main Authors: Teh, Audrey Y‐H., Maresch, Daniel, Klein, Katja, Ma, Julian K‐C.
Format: Article
Language:English
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Summary:Summary The proposed clinical trial in A frica of VRC 01, a potent broadly neutralizing antibody (b NA b) 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‐ S aharan A frica. Here, we report the expression of VRC 01 in plants as an economic alternative to conventional mammalian‐cell‐based production platforms. The heavy and light chain genes of VRC 01 were cloned onto a single vector, p TRA k.2, which was transformed into N icotiana benthamiana or N icotiana tabacum using transient and stable expression production systems respectively. VRC 01 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 VRC 01 from both systems showed a largely homogeneous N ‐glycosylation profile with a single dominant glycoform. The binding kinetics to gp120 IIIB (approximately 1 n m ), neutralization of HIV ‐1 B a L or a panel of 10 VRC 01‐sensitive HIV ‐1 E nv pseudoviruses of VRC 01 produced in transient and stable plants were also consistent with VRC 01 from HEK cells.
ISSN:1467-7644
1467-7652
DOI:10.1111/pbi.12137