Efficacy test of monoclonal antibody prepared by PBJ plants against the BA.5 variant of the new crown

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists globally, along with the emergence of immunoevasive variants, and most monoclonal antibodies (mAbs), which are used as therapies for SARS-CoV-2 infection, have thus lost their utility
against the variant and its subvariants 。 On December 15, 2022, Plant Biotechnology Journal published a research paper online: "The potency and synergy of plant-made monoclonal antibodies against the BA.
5 variant of SARS-CoV-2".
ACE2-based therapeutics have developed monoclonal antibodies containing two new versions of mAbs, tixagevimab and cilgavimab, plant-derived mAbs that effectively neutralize multiple subforms of SARS-CoV-2 and are more potent
against variants including BA.
5 and BA.
4.
6.

The authors fused variable region genes of tixagevimab and cilgavimab onto a human IgG1 backbone and then transiently transiently these mAbs in transgenic ΔXFT Benthamiana in which the glycosyltransferase used to synthesize plant-specific xylose and core fucose has been stably knocked out (RNAi).

。 The expression of cilgavimab (pCilgavimab) in plants peaked at about 726 μg/g fresh leaf weight (FLW) 6 days after Agrobacterium infiltration, and the expression of tixagevimab (pTixagevimab) peaked one day earlier, at about 403 μg mAb/g FLW
。 Carbohydrate analysis of conservative Fc glycosomes showed that both mAbs contained highly homogeneous N-linked sugars, and both mAbs specifically identified RBD for SARS-CoV-2 and neutralized variants (B.
1.
1.
529) in lesion formation assays, with IC50s of 2.
23 μg/ml and 19.
68 μg/ml
, respectively 。 To analyze the neutralizing synergistic effect of pCilgavimab and pTixagevimab as dual mAb mixed antibodies on Omicron SARS-CoV-2, the authors mixed mAbs and performed single mAb replication at their respective IC20, IC25, and IC50 concentrations, using four models from the SynergyFinder.
org website to analyze the percent neutralization values
of individual mAbs.
It was found that pCilgavimab and pTixagevimab showed synergy at all three test concentrations
.

The authors further tested two plant-expressed mAbs against the BA.
4/5 Omicron subvariant with a pseudovirus-based neutralization experiment, and found that both pCilgavimab and pTixagevimab neutralized BA.
4/5, consistent with previous findings, with increased efficacy of cilgavimab against BA.
4/5 pseudoviruses and decreased efficacy of tixagevimab against BA.
4/5
。 In addition, the neutralizing synergy observed by the two mAbs against the B.
1.
1.
529 variant carried over to the BA.
4/5 variant, albeit with reduced potency, against the latest dominant variant BA.
4.
6 (Table S1), which has been shown to be resistant to all other mAbs developed to date
.

This is the first report to produce the two mAbs that make up Evusheld in plants, and the first collaborative analysis
of the Omicron variant by mixed antibodies.
Both mAbs neutralize multiple SARS-CoV-2 variants, with pCilgavimab being more
potent than pTixagevimab in neutralizing B.
1.
1.
529 and BA.
4/5 variants.
As a combination, these mAbs showed a synergistic effect of neutralization against the parental Omicron variant and remained effective
against the BA.
4/5 and BA.
4.
6 variants.
The authors speculate that mAbs expressed in these plants may be more effective than mAbs expressed in mammals, laying a solid foundation
for the development of stable and effective mAbs based on plants as therapeutic agents for SARS-CoV-2.

https://onlinelibrary.
wiley.
com/doi/epdf/10.
1111/pbi.
13980

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