Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 May 29;12(6):895.
doi: 10.3390/jpm12060895.

VH3-53/66-Class RBD-Specific Human Monoclonal Antibody iB20 Displays Cross-Neutralizing Activity against Emerging SARS-CoV-2 Lineages

Sergey V Kulemzin  1 , Maria V Sergeeva  2 , Konstantin O Baranov  1 , Andrey A Gorchakov  1 , Sergey V Guselnikov  1 , Tatyana N Belovezhets  1 , Olga Yu Volkova  1 , Alexander M Najakshin  1 , Nikolai A Chikaev  1 , Daria M Danilenko  2 , Alexander V Taranin  1
Affiliations

VH3-53/66-Class RBD-Specific Human Monoclonal Antibody iB20 Displays Cross-Neutralizing Activity against Emerging SARS-CoV-2 Lineages

Sergey V Kulemzin et al. J Pers Med. .

Abstract

Immune evasion of SARS-CoV-2 undermines current strategies tocounteract the pandemic, with the efficacy of therapeutic virus-neutralizing monoclonal antibodies (nAbs) being affected the most. In this work, we asked whether two previously identified human cross-neutralizing nAbs, iB14 (class VH1-58) and iB20 (class VH3-53/66), are capable of neutralizing the recently emerged Omicron (BA.1) variant. Both nAbs were found to bind the Omicron RBD with a nanomolar affinity, yet they displayed contrasting functional features. When tested against Omicron, the neutralizing activity of iB14 was reduced 50-fold, whereas iB20 displayed a surprising increase in activity. Thus, iB20 is a unique representative of the VH3-53/66-class of nAbs in terms of breadth of neutralization, which establishes it as a candidate for COVID-19 therapy and prophylactics.

Keywords: COVID-19; Omicron; SARS-CoV-2; VH1-58; VH3-53/66; iB14; iB20; mutational escape; neutralizing monoclonal antibodies; variants of concern.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
BLI analysis of the interaction between nAbs iB14 and iB20 (9–36 nM) with the indicated RBDs of SARS-CoV-2 and SARS-CoV.
Figure 2
Figure 2
Activity of iB14 and iB20 in pseudovirus (A) and authentic SARS-CoV-2 (B) virus-neutralization assays. Early pandemic (Wuhan-1 or B.1) and Omicron variants were used.
Figure 3
Figure 3
Competition BLI assay for iB20 and CV30 binding to SARS-CoV-2 RBD.
See this image and copyright information in PMC

References

    1. Raybould M.I.J., Kovaltsuk A., Marks C., Deane C.M. CoV-AbDab: The coronavirus antibody database. Bioinformatics. 2021;37:734–735. doi: 10.1093/bioinformatics/btaa739. - DOI - PMC - PubMed
    1. Wibmer C.K., Ayres F., Hermanus T., Madzivhandila M., Kgagudi P., Oosthuysen B., Lambson B.E., De Oliveira T., Vermeulen M., Van Der Berg K., et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat. Med. 2021;27:622–625. doi: 10.1038/s41591-021-01285-x. - DOI - PubMed
    1. Abdool Karim S.S., De Oliveira T. New SARS-CoV-2 Variants—Clinical, Public Health, and Vaccine Implications. N. Engl. J. Med. 2021;384:1866–1868. doi: 10.1056/NEJMc2100362. - DOI - PMC - PubMed
    1. Dejnirattisai W., Zhou D., Supasa P., Liu C., Mentzer A.J., Ginn H.M., Zhao Y., Duyvesteyn H.M.E., Tuekprakhon A., Nutalai R., et al. Antibody evasion by the P.1 strain of SARS-CoV-2. Cell. 2021;184:2939–2954. doi: 10.1016/j.cell.2021.03.055. - DOI - PMC - PubMed
    1. Wang P., Nair M.S., Liu L., Iketani S., Luo Y., Guo Y., Wang M., Yu J., Zhang B., Kwong P.D., et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature. 2021;593:130–135. doi: 10.1038/s41586-021-03398-2. - DOI - PubMed

LinkOut - more resources