Characterisation of a highly potent and near pan-neutralising anti-HIV monoclonal antibody expressed in tobacco plants

Moore, Catherine M., Grandits, Melanie, Grünwald-Gruber, Clemens, Altmann, Friedrich, Kotouckova, Maria, Teh, Audrey Y-H and Ma, Julian K-C 2021. Characterisation of a highly potent and near pan-neutralising anti-HIV monoclonal antibody expressed in tobacco plants. Retrovirology. 18 17. https://doi.org/10.1186/s12977-021-00560-6

TitleCharacterisation of a highly potent and near pan-neutralising anti-HIV monoclonal antibody expressed in tobacco plants
TypeJournal article
AuthorsMoore, Catherine M., Grandits, Melanie, Grünwald-Gruber, Clemens, Altmann, Friedrich, Kotouckova, Maria, Teh, Audrey Y-H and Ma, Julian K-C
Abstract

Background
HIV remains one of the most important health issues worldwide, with almost 40 million people living with HIV. Although patients develop antibodies against the virus, its high mutation rate allows evasion of immune responses. Some patients, however, produce antibodies that are able to bind to, and neutralise different strains of HIV. One such ‘broadly neutralising’ antibody is ‘N6’. Identified in 2016, N6 can neutralise 98% of HIV-1 isolates with a median IC50 of 0.066 µg/mL. This neutralisation breadth makes N6 a very promising therapeutic candidate.

Results
N6 was expressed in a glycoengineered line of N. benthamiana plants (pN6) and compared to the mammalian cell-expressed equivalent (mN6). Expression at 49 mg/kg (fresh leaf tissue) was achieved in plants, although extraction and purification are more challenging than for most plant-expressed antibodies. N-glycoanalysis demonstrated the absence of xylosylation and a reduction in α(1,3)-fucosylation that are typically found in plant glycoproteins. The N6 light chain contains a potential N-glycosylation site, which was modified and displayed more α(1,3)-fucose than the heavy chain. The binding kinetics of pN6 and mN6, measured by surface plasmon resonance, were similar for HIV gp120. pN6 had a tenfold higher affinity for FcγRIIIa, which was reflected in an antibody-dependent cellular cytotoxicity assay, where pN6 induced a more potent response from effector cells than that of mN6. pN6 demonstrated the same potency and breadth of neutralisation as mN6, against a panel of HIV strains.

Conclusions
The successful expression of N6 in tobacco supports the prospect of developing a low-cost, low-tech production platform for a monoclonal antibody cocktail to control HIV in low-to middle income countries.

Article number17
JournalRetrovirology
Journal citation18
ISSN1742-4690
Year2021
PublisherSpringer
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1186/s12977-021-00560-6
Web address (URL)https://europepmc.org/articles/PMC8240387
Publication dates
Published28 Jun 2021

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