Soumya Shraddhya Paul, Amity University Noida
For a very long time, monoclonal antibodies have been used in various fields (cancer studies) but currently, they are being used to counteract the effects of SARS-CoV-2 and its variant by being an active compound in the vaccine as well as therapeutic drugs. Hence, to understand B cell genomics behind its response towards SARS-CoV-2 scientists combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures. The main function of the B cells is to produce antibodies, for SARS-CoV-2 B cells have distinct antibodies also known as neutralizing antibodies (nAbs). Research has shown one of the mAbs, BG10-19 has the potential to neutralize SARS-CoV-2 and its mutant B.1.1.7 as well as B.1.351.
Brief about the Study
When SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus) happened, a few neutralizing monoclonal antibodies were isolated. This was done using phage display technique and Epstein Barr virus-transformed B cells. To learn more about antiviral antibodies and B cells subpopulation we integrated single-cell RNA sequencing of B cells with functional testing and structural characterization of selected mAbs this gave us detail about transcriptional pathways.
To create therapeutic advances in mAbs showed how SARS-CoV-2 spike binds to its angiotensin-converting enzyme 2 (ACE2) receptor, this also showed the polyclonal antibodies responses in COVID-19.
Therefore to understand more about B cell genomics and their response researchers used scRNA-seq to investigate SARS-CoV-2 spike-specific B cell responses, in 14 of the recently recovered COVID-19 subjects. Here they matched the functional studies of 92 mAbs with VDJ sequencing and transcriptional profile of the subjects this gave them two transcriptional structures from where a majority of the neutralizing antibodies (nAb) are taken. Out of this, it was seen that 6 of the most potent nAbs from B cells including BG10-19 was seen to have reached between the adjacent RBDs in spike trimer locking it in such a manner that it cannot bind ACE2. This neutralizes the effects of SARS-CoV-2 and its variant B.1.1.7 and B.1.351.
Results
Here we see 14 subjects who had COVID-19 and showed serum neutralization activity, they were used to under the effect of B cells on SARS-CoV-2. It’s important to note here that none of these 14 subjects required hospitalization.
To understand the neutralization effects they used pseudotyped virus with SARS-CoV-2 spike (S) protein and 11 of the 14 subjects showed serum neutralization. After this total of 6,113 B cells were isolated from all the subjects who specifically bind with RBDs and S protein. After this, they performed the rest of the exams such as whether the B cells underwent any somatic variations or the presence of Ig genes VH3-53 and VH3-66 with short CDRH3 regions.
From this 4 out of the 14 subjects were chosen who showed the highest serum neutralization titers as donors, from them a total of 92 mAbs were isolated. Out of these 56 showed strong binding towards RBDs, S and SARS-COV-2 or both, 42 out of the 56 showed strong bonding towards RBDs, S and SARS-CoV-2, 9 of them showed strong bound towards SARS-CoV-2, S and lastly 5 showed only to RBDs all of these was checked through ELISA.
It was seen that mAbs isolated from RBD-binding B cells were typically non-polyreactive i.e., they don’t attach to non-specific antigens, neutralizing antibodies mostly arise from IgG+B cells and target RBDs, IgA dimerization also helps in neutralization, BG10-19 is seen to be effective towards both SARS-CoV-2 and SARS-CoV it was also seen that selected mAbs were also potent towards the new circular variants.
Conclusion
Through this study, scientists have tried to show that immunogenic correlates protection against SARS-CoV-2 through vaccination or prior exposure is not yet defined but it is important to note here that various studies conducted on other respiratory viruses have shown that serum neutralization can help us fight against SARS-CoV-2.
There is also a limitation to this study as not all the TCs were functionally evaluated. Due to limited membership. And the affinity of various antibodies used in this study can be improved in various in vivo conditions.
Also read: Etheno Adducts of Nucleic Acids and their Carcinogenic Aspects
References:
- Scheid, J. F., Barnes, C. O., Eraslan, B., Hudak, A., Keeffe, J. R., Cosimi, L. A., Brown, E. M., Muecksch, F., Weisblum, Y., Zhang, S., Delorey, T., Woolley, A. E., Ghantous, F., Park, S.-M., Phillips, D., Tusi, B., Huey-Tubman, K. E., Cohen, A. A., Gnanapragasam, P. N. P., … Xavier, R. J. (2021). B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV. Cell, 184(12), 3205-3221.e24. https://doi.org/10.1016/j.cell.2021.04.032
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About author:
Soumya Shraddhya Paul is an undergrad biotechnology student who worked in building 3D prosthetics in Base Hospital Delhi Cantt, and holds a key interest in neutraceuticals and enzymology. She is inclined towards scientific writing and takes keen interest in writing quality articles. Her previous publication at BioXone is:
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