A novel plant‐made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS‐CoV‐2 Omicron variant

Abstract

Summary This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan‐Hu‐1 RBD of SARS‐CoV‐2. We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human‐like, highly homogenous N‐linked glycans that has potential to impart greater potency and safety as a therapeutic. The epitope of 11D7 was mapped by competitive binding with well‐characterized mAbs, suggesting that it is a Class 4 RBD‐binding mAb that binds to the RBD outside the ACE2 binding site. Of note, 11D7 maintains recognition against the B.1.1.529 (Omicron) RBD, as well neutralizing activity. We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. Taken together, 11D7 is a unique mAb that neutralizes SARS‐CoV‐2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety‐friendly alternative platform for generating mAbs to address the evolving SARS‐CoV‐2 crisis.

Antibody-Dependent Enhancement Activity of a Plant-Made Vaccine against West Nile Virus

“…In response, we explored our plant-expression system to express wDIII, an antigen with defined neutralizing, but avoid immune-pathological epitopes in the form of VLPs, to address safety issue and vaccine production challenges since plants can produce recombinant proteins at manufacturing scale inexpensively [ 35 , 36 , 37 ] with potent efficacy [ 38 , 39 , 40 , 41 ]. We reported previously that high-yield production of HBcAg-wDIII VLPs was achieved in Nicotiana benthamiana leaves within days of introducing the target gene and the VLPs displayed the wDIII epitopes authentically on their surfaces [ 13 ].…”

A Dual-Approach Strategy to Optimize the Safety and Efficacy of Anti-Zika Virus Monoclonal Antibody Therapeutics

“…The genes for the variable regions of the heavy chain (HC) and light chain (LC) of ZV54 [ 8 ] were synthesized and cloned into vectors containing the coding sequence of the human IgG1 HC constant region and the kappa LC constant region, respectively [ 27 ]. The resulting HC and LC genes were cloned into MagnICON-based plant expression vectors and transformed into A. tumefaciens as described previously [ 28 ].…”

A genome‐edited N. benthamiana line for industrial‐scale production of recombinant glycoproteins with targeted N‐glycosylation

“…No differences in glycan profiles or protein assembly were observed (Figure S9). Previously an N. benthamiana RNAi-based XylT and FucT knockdown mutant (ΔXT/FT) [18] which is widely used by academia and industry, for example, [19][20][21][22][23] was developed. A direct comparison of the glycosylation profiles of glyco-reporters produced in NbXF-KO and ΔXT/FT revealed significant amounts of fucose (up to 25%) on some ΔXT/FT produced proteins, for example, IgA and IgM (Figure S7, Table S10).…”