key: cord-0888471-lhx0it2z
authors: Hoffmann, Markus; Hofmann-Winkler, Heike; Krüger, Nadine; Kempf, Amy; Nehlmeier, Inga; Graichen, Luise; Sidarovich, Anzhalika; Moldenhauer, Anna-Sophie; Winkler, Martin S.; Schulz, Sebastian; Jäck, Hans-Martin; Stankov, Metodi V.; Behrens, Georg M. N.; Pöhlmann, Stefan
title: SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination
date: 2021-05-05
journal: bioRxiv
DOI: 10.1101/2021.05.04.442663
sha: 60b301f22b21428f6c03974de692d9e9b0fbce6e
doc_id: 888471
cord_uid: lhx0it2z

The emergence of SARS-CoV-2 variants threatens efforts to contain the COVID-19 pandemic. The number of COVID-19 cases and deaths in India has risen steeply in recent weeks and a novel SARS-CoV-2 variant, B.1.617, is believed to be responsible for many of these cases. The spike protein of B.1.617 harbors two mutations in the receptor binding domain, which interacts with the ACE2 receptor and constitutes the main target of neutralizing antibodies. Therefore, we analyzed whether B.1.617 is more adept in entering cells and/or evades antibody responses. B.1.617 entered two out of eight cell lines tested with slightly increased efficiency and was blocked by entry inhibitors. In contrast, B.1.617 was resistant against Bamlanivimab, an antibody used for COVID-19 treatment. Finally, B.1.617 evaded antibodies induced by infection or vaccination, although with moderate efficiency. Collectively, our study reveals that antibody evasion of B.1.617 may contribute to the rapid spread of this variant.

expression rendered these cells susceptible to S protein-driven entry and entry efficiency was 193 and it is believed that these antibody responses are important for protection from re-infection 194 (Rodda et al., 2021; Wajnberg et al., 2020) . Therefore, we determined whether variant B.1.617 195 evades inhibition by antibodies, which might contribute to its increasing transmission dynamics.

For this, we analyzed antibody-mediated neutralization using plasma samples obtained from 15 197 COVID-19 patients at the intensive care unit of Göttingen University Hospital (Table S1 ). These Therefore, we analyzed whether cell entry driven by the S protein of variant B.1.617 can be 215 efficiently inhibited by plasma from Comirnaty/BNT162b2 vaccinated individuals (Table S2) . To 216 address this question, we analyzed neutralization by 15 plasma samples obtained from vaccinees 217 two to three weeks after they had received the second vaccine dose. All sera efficiently inhibited 218 entry driven by WT S protein ( Figure 5B and Figure S3B ). Inhibition of entry driven by B.1.351 219 S protein was more than 11-fold reduced as compared to WT ( Figure 5B ), in keeping with Color code: light blue, S1 subunit with RBD in dark blue; gray, S2 subunit; orange, S1/S2 and 694 S2' cleavage sites; red, mutated amino acid residues. Figure S1 . Transduction data normalized against the assay background (related to Figure 2 ).

The experiment was performed as described in the legend of Figure 1A . Presented are the average 769 (mean) data from the same three biological replicates (each conducted with technical 770 quadruplicates) as presented in Figure 1A with the difference that this time transduction was to calculated the plasma/serum dilution that leads to 50% reduction in S protein-driven cell entry 796 (neutralizing titer, NT50, shown in Figure 5 ). 797 Table S1 798 

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