Kanikah Mehndiratta, MSc, University of Glasgow
The SARS-CoV2 virus has been nothing less than devastating to the global population within the last 1 year. The associated COVID-19 (coronavirus disease-2019) is being the center of attention for scientists and doctors worldwide. It helps them understand the underlying pathophysiology so that they can work towards devising appropriate therapeutics. The research behind how the body’s immune system is responding to different variants of the SARS-CoV2 virus is crucial to predict the efficacy of vaccines against continuously evolving viral strains.
The memory B cells play an important role in the antibody response against recurrent COVID-19 infection. Recent research by the Harvard Medical School, MIT along with collaborators that will soon be published in the Cell, has generated a global repertoire. The atlas of the memory B cells against the specific S spike proteins would help in understanding robust responses to the different viral strains.
Antibodies against SARS-CoV2 viral strains:
In the last couple of months, many viral strains of the same SARS-CoV2 virus have evolved globally from B.1.1.7 and the B.1.351 to the latest Delta strain (B.1.617.2). Vaccine development has been remarkable, but research needs to be done against the efficacy of such vaccines against different strains. This requires a better understanding of how the viral strains are recognized by the memory B cells. This could help devise strategies regarding broad specific immunity. Antibodies or immunoglobulins are produced by the immune system for defending against specific pathogens. They are both soluble effector molecules and part of the memory B cells antigen receptor complex.
The complex tries to promote effective binding of antigens from the pathogen by somatic hypermutations in the immunoglobulin gene and their selection in the germinal centers of lymphoid tissues. This results in an antibody affinity maturation and the release of plasma cells that are secreting those antibodies. Then, there are the memory B cells that would remember how to respond to future infection by a similar antigen. A lot of recent data is showing the high efficacy of different vaccines against new SARS-CoV2 viral strains, but the study focuses on the antibody response in the same scenario.
The most effective booster vaccine could be developed only by analyzing how the repertoire of different antibodies recognize the mutated S glycoprotein of the viral strains. Antibodies target these via both complementary and competitive recognition. There is substantial research into the specific antibodies’ identification and characterization. However, the recognition reach of the memory cells induced by one of the strains towards newer strains across major epitopes doesn’t hold much clarity.
Research Strategy and Findings:
A global assessment of cooperative and competitive recognition clusters encompassing different antibodies and their robustness against the different viral strains has been the center of the study. 152 monoclonal antibodies from 19 convalescent COVID-19 patients expressing mild symptoms have been examined for their binding affinities to different S glycoprotein models, such as Alpha, Beta, and Gamma.
7 major footprints of the perfusion stabilized trimeric S ectodomain were identified using Flow cytometry, ELISA, and other competitive analysis strategies. Amongst these, 3 with epitopes on the receptor-binding domain, 2 competition groups with epitopes on the N-terminal domain, and 2 others were identified for the S2 epitopes. The first 2 domains were considered potent neutralizers while the S2 domain had the highest recognition breadth across the different viral strains. The Beta variant escapes binding by the potent neutralizers. But conclusively the redundant nature of the memory B cells for a specific epitope region can provide high recognition breadth for other mutating variants too.
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References:
- Tong, P., Gautam, A., Windsor, I. W., Travers, M., Chen, Y., Garcia, N., Whiteman, N. B., McKay, L. G. A., Storm, N., Malsick, L. E., Honko, A. N., Lelis, F. J. N., Habibi, S., Jenni, S., Cai, Y., Rennick, L. J., Duprex, W. P., McCarthy, K. R., Lavine, C. L., … Wesemann, D. R. (2021). Memory b cell repertoire for recognition of evolving SARS-Cov-2 spike. Cell, S0092867421008849. https://doi.org/10.1016/j.cell.2021.07.025
- Kumar, R., Nagpal, S., Kaushik, S., & Mendiratta, S. (2020). COVID-19 diagnostic approaches: Different roads to the same destination. VirusDisease, 31(2), 97–105. https://doi.org/10.1007/s13337-020-00599-7
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Author info:
Kanikah Mehndiratta is an avid researcher in the field of Genetics with a background in Biotechnology. She is a postgraduate from the University of Glasgow in their Medical Genetics and Genomics program. Currently, based in Chandigarh as a scientific writer, she involves herself mainly in projects related to neurological disorders. Outside of academics, she likes to read novels, travel and is involved in volunteer work mostly.
LinkedIn profile- https://www.linkedin.com/in/kanikah-mehndiratta-301830171
Other articles-
2. https://bioxone.in/news/worldnews/iga-virus-immune-complex-neutrophils-trap-for-sars-cov-2/
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