A plant-based monoclonal antibody increases the potency of an antibody cocktail against the SARS-CoV-2 Omicron variant


The rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the novel coronavirus 2019 (COVID-19) pandemic.

Since the beginning of the pandemic, many SARS-CoV-2 variants have emerged as a result of genetic mutations. Many of these variants have been classified as variants of interest (VOI) and variants of concern (VOC) based on their virulence, transmissibility, and ability to evade immunity induced by natural infection and vaccination against COVID-19.

Study: A plant-based monoclonal antibody enhances the synergistic activity of an antibody cocktail against the Omicron SARS-CoV-2 variant.  Image credit: ustas7777777 / Shutterstock.com

Stady: The novel plant monoclonal antibody enhances the synergistic potency of the antibody cocktail against the Omicron SARS-CoV-2 variant. Image credit: ustas7777777 / Shutterstock.com

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Preventive and therapeutic monoclonal antibodies (mAbs) play an important role in protecting vulnerable populations from infection with COVID-19. For example, vaccination does not effectively protect immunocompromised individuals from SARS-CoV-2 infection, because they may not develop significant and lasting immunity after vaccination.

Where effectiveness COVID-19 vaccines against volatile organic compounds have been reduced, and more effective treatments are needed to protect the global population from existing and emerging SARS-CoV-2 strains.

Usually, mAbs can prevent viral infection by neutralizing the virus. Based on the epitope, which recognizes the receptor-binding domain (RBD) of SARS-CoV-2 Spike proteinmAbs were classified into four groups ranging from classes 1–4.

Among the classes, class 1 and 2 mAbs, which interact with the angiotensin-converting enzyme 2 (ACE2)-binding site of RBD, have the greatest neutralizing ability. It is important to characterize mAbs in these categories, as it aids in the development of effective mAb cocktails that reduce immune evasion.

Over the past two years, several SARS-CoV-2-specific mAbs have received emergency authorization (EUA) from the US Food and Drug Administration (FDA) to combat SARS-CoV-2 infection. However, some of these fatty acids were subsequently modified or abolished, as they lost therapeutic efficacy against newly emerged SARS-CoV-2 variants, in particular the B.1.1.529 variant (Omicron) and its sub-variants.

Thus, there remains an urgent need to develop new mAb cocktails that are effective against the currently circulating Omicron variant, along with other SARS-CoV-2 variants.

Plants are promising systems for the production of recombinant proteins. One previous clinical study showed that a newly synthesized COVID-19 vaccine was safe and highly effective in preventing infection. Since then, this vaccine has been approved for human use in Canada.

about studying

In contrast to conventional methods, using plants to develop mAbs does not require sterile facilities and expensive protocols. newly Journal of Plant Biotechnology The study discusses the development of a novel mAb against SARS-CoV-2 RBD through hybridoma technology, followed by imaging and expression in plants.

In this study, an enzyme-linked immunosorbent assay (ELISA) was used for primary screening of mAbs, which were synthesized by hybridomas generated from mice vaccinated with RBD. After the screening process, the 11D7 mAb was selected for its recombinant expression in plants. This mAb was chosen based on its ability to efficiently neutralize the SARS-CoV-2 progenitor strain in the foci formation assay (FFA).

Results

Chimeric 11D7 expression in ΔXFT Nicotiana bentameana It peaked within 1 week of agrofiltration to about 131 μg of p11D7 per gram of fresh leaf weight (FLW). Although the level of 11D7 mAb produced in the plant system was promising, it was lower than mAbs produced in other retroviral vectors.

11D7 was produced in N. Bentamiana Plants can be improved through the use of improved forms of expression vectors and/or through co-expression with chaperones. The improvement will enable the commercialization of the product to combat COVID-19.

Western blot analysis indicated that the recombinant plant-derived 11D7 (p11D7) perfectly assembled into immunoglobulin G (IgG) without any degradation or prominent truncation of the heterologous protein. The dissociation constant estimated using ELISA was 0.15 nM, which strongly indicated that the new mAb had high affinity for SARS-CoV-2 RBD.

This value was comparable to other neutralizing mAbs against SARS-CoV-2, such as CA1 and CB6 that are produced in plants. However, the 50% inhibitory concentration (IC50) of p11D7 to neutralize the SARS-CoV-2 progenitor strain was significantly higher than other plant mAbs at 25.37 μg/ml.

The authors speculated that p11D7 could neutralize viral particles by a mechanism other than interfering with ACE2 binding. One of the most important findings of this study was the ability of p11D7 to bind to and thus neutralize Omicron RBD. This novel mAb also retained its neutralizing ability against the delta variant.

Experimental results indicated that p11D7, which overlaps with class 4 mAbs, could be a promising candidate for complementing other classes of mAbs in a cocktail formulation. This is an important observation, as mAb cocktails can provide synergistic potency against multiple variants.

To this end, the authors used binary and triple combinations of p11D7 with other plant-made mAbs, such as cilgavimab and tixagevimab, and studied its efficacy against the Omicron variant. The triple mAb combination showed maximum neutralizing activity compared to all dual combinations.

conclusions

A major advantage of developing effective plant-based mAbs is their lower cost of production compared to conventional procedures that require mammalian systems and sophisticated facilities. The present study showed that mAb p11D7 extracted from the new plant was safe and highly effective against the SARS-CoV-2 variant Omicron.

Journal reference:

  • Jugler, C., Sun, H., Nguyen, K., et al. (2022). The novel plant monoclonal antibody enhances the synergistic potency of the antibody cocktail against the Omicron SARS-CoV-2 variant. Journal of Plant Biotechnology. doi: 10.1111/pbi.13970



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