[Source: MedRxIV, full page: (LINK). Abstract, edited.]
Bamlanivimab does not neutralize two SARS-CoV-2 variants carrying E484K in vitro
Marek Widera, Alexander Wilhelm, Sebastian Hoehl, Christiane Pallas, Niko Kohmer, Timo Wolf, Holger F Rabenau, Victor M Corman, Christian Drosten, Maria JGT Vehreschild, Udo Goetsch, Rene Gottschalk, Sandra Ciesek
doi: https://doi.org/10.1101/2021.02.24.21252372 | This article is a preprint and has not been certified by peer review. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
The IgG1 monoclonal antibody (mAb) bamlanivimab (LY-CoV555) prevents viral attachment and entry into human cells by blocking attachment to the ACE2 receptor. However, whether bamlanivimab is equally effective against SARS-CoV-2 emerging variants of concern (VOC) is not fully known. Hence, the aim of this study was to determine whether bamlanivimab is equally effective against SARS-CoV-2 emerging VOC. The ability of bamlanivimab to neutralize five SARS-CoV-2 variants including B.1.1.7 (mutations include N501Y and del69/70), B.1.351 (mutations include E484K and N501Y) and P.2 (mutations include E484K in the absence of a N501Y mutation) was analyzed in infectious cell culture using CaCo2 cells. Additionally, we analyzed vaccine-elicited sera after immunization with BNT162b2, and convalescent sera for its ability to neutralize SARS-CoV-2 variants. We found that the variant B.1.1.7, as well as two isolates from early 2020 (FFM1 and FFM7) could be efficiently neutralized by bamlanivimab (titer 1/1280, respectively), however, no neutralization effect could be detected against either B.1.135 or P.2, both harboring the E484K substitution. Vaccine-elicited sera showed slightly decreased neutralizing activity against B1.1.7, B.1.135 and P.2 Our in vitro findings indicate that, in contrast to vaccine-elicited sera, bamlanivimab may not provide efficacy against SARS-CoV-2 variants harboring the E484K substitution. Confirmation of the SARS-CoV-2 variant, including screening for E484K, may be needed before initiating mAb treatment with bamlanivimab to ensure both efficacious and efficient use of the antibody product. Hence, variant-specific mAb agents may be required to treat emerging VOC.
Competing Interest Statement: The authors have declared no competing interest.
Funding Statement: No external funding was received
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Ethik-Kommission des Fachbereiches Medizin der Goethe Universitaet Frankfurt (250719)
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Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv
Copyright – The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Keywords: SARS-CoV-2; COVID-19; Monoclonal antibodies; E484K; Immune escape.
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