SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination

Hoffmann, Markus; Hofmann-Winkler, Heike; Krueger, Nadine; Kempf, Amy; Nehlmeier, Inga; Graichen, Luise; Sidarovich, Anzhalika; Moldenhauer, Anna-Sophie; Winkler, Martin Sebastian; Schulz, Sebastian; Jaeck, Hans-Martin; Stankov, Metodi V.; Behrens, Georg M. N.; Poehlmann, Stefan

doi:10.1101/2021.05.04.442663

Cited by 96 publications

(82 citation statements)

References 60 publications

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“…India is facing a large surge in COVID-19 cases since early 2021. Many cases are caused by a new lineage, termed B.1.617 [1][2][3][4][5][6] . The epidemiology data are scarce, but B.1.617 has become the predominant strain in the state of Maharashtra and probably in other Indian regions 4 .…”

Section: Introductionmentioning

confidence: 99%

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Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

Planas

Veyer

Baidaliuk

et al. 2021

Preprint

277

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The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India. It has since then become dominant in some indian regions and further spread to many countries. The lineage includes three main subtypes (B1.617.1, B.1617.2 and B.1.617.3), which harbour diverse Spike mutations in the N-terminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2 is believed to spread faster than the other versions. Here, we isolated infectious B.1.617.2 from a traveller returning from India. We examined its sensitivity to monoclonal antibodies (mAbs) and to antibodies present in sera from COVID-19 convalescent individuals or vaccine recipients, in comparison to other viral lineages. B.1.617.2 was resistant to neutralization by some anti-NTD and anti-RBD mAbs, including Bamlanivimab, which were impaired in binding to the B.1.617.2 Spike. Sera from convalescent patients collected up to 12 months post symptoms and from Pfizer Comirnaty vaccine recipients were 3 to 6 fold less potent against B.1.617.2, relative to B.1.1.7. Sera from individuals having received one dose of AstraZeneca Vaxzevria barely inhibited B.1.617.2. Thus, B.1.617.2 spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes.

show abstract

Section: Introductionmentioning

confidence: 99%

“…

The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India [1][2][3][4][5][6] . It has since then become dominant in some indian regions and further spread to many countries.

…”

mentioning

confidence: 99%

Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

Planas

Veyer

Baidaliuk

et al. 2021

Preprint

277

View full text Add to dashboard Cite

show abstract

“…We also identified seven patients with COVID-19 caused by B.1.617.1 or B.1.617.2, variants reported to be causing widespread disease and extensive public health concern in India. [43][44][45][46][47][48] In the aggregate, our genome data show that VOC and VOI now account for the great majority of all new COVID-19 cases in our region.…”

Section: [Introduction]mentioning

confidence: 63%

Trajectory of Growth of SARS-CoV-2 Variants in Houston, Texas, January through May 2021 Based on 12,476 Genome Sequences

Olsen

Christensen

Long

et al. 2021

Preprint

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Genetic variants of the SARS-CoV-2 virus are of substantial concern because they can detrimentally alter the trajectory of the ongoing pandemic, and disease course in individual patients. Here we report genome sequences from 11,568 COVID-19 patients in the Houston Methodist healthcare system dispersed throughout the metroplex that were diagnosed from January 1, 2021 through April 30, 2021. This sample represents 94% of Houston Methodist cases and 4.6% of all reported cases in the metropolitan area during this period. The SARS-CoV-2 variant designated UK B.1.1.7 increased very rapidly, and now causes 75%-90% of all new cases in the Houston area. Five of the 2,543 B.1.1.7 genomes had an E484K change in spike protein. Compared with non-B.1.1.7 patients, individuals infected with B.1.1.7 had a significantly lower cycle threshold value (considered to be a proxy for higher virus load) and higher rate of hospitalization. Other variants (e.g., B.1.429, B.1.427, P.1, P.2, and R.1) also increased rapidly in frequency, although the magnitude was less than for B.1.1.7. We also identified 42 patients with a recently described R.1 variant that has an E484K amino acid replacement, and seven patients with the B.1.617 "India" variants. In the aggregate, our study shows the occurrence of a diverse array of concerning SARS-CoV-2 variants circulating in a major metropolitan area, documents B.1.1.7 as the major cause of new cases in Houston and heralds the arrival and spread of B.1.617 variants in the metroplex.

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“…Actually, in their preprint work Hoffmann et al analyzed whether the SARS-CoV-2 VOC B.1.617 is more adept in entering cells and/or evade Ab responses. 85 They found that B.1617 entered two out of 8 cell lines tested (specifically, the human lung-and intestine-derived Calu-3 and Caco-2 cell lines, respectively) with slightly increased efficiency, and was blocked by an entry inhibitor. However, in stark contrast, B.1.167 was found to be fully resistant to LY-CoV555 and partially resistant against neutralization by Abs elicited upon infection or vaccination with the Comirnaty/Pfizer-BioNTech vaccine.…”

Section: δδGmentioning

confidence: 99%

In Silico Molecular-Based Rationale for SARS-CoV-2 Spike Circulating Mutations Able to Escape Bamlanivimab and Etesevimab Monoclonal Antibodies

Laurini

Aulić

Fermeglia

et al. 2021

Preprint

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The purpose of this work was to provide an in silico molecular rationale of the role eventually played by currently circulating S-RBDCoV‑2 mutations in evading the immune surveillance effects elicited by the two Eli Lilly LY-CoV555/bamlanivimab and LY-CoV016/etesevimab monoclonal antibodies. The main findings from this study and shows that, compared to the wild-type SARS-CoV-2 spike protein, mutations E484A/G/K/Q/R/V, Q493K/L/R, S494A/P/R, L452R and F490S are predicted to be markedly resistant to neutralization by LY-CoV555, while mutations K417E/N/T, D420A/G/N, N460I/K/S/T, T415P, and Y489C/S are predicted to confer LY-CoV016 escaping advantage to the viral protein. A challenge of our global in silico results against the relevant experimental data resulted in an overall 90% agreement. This achievement not only constitutes a further, robust validation of our computer-based approach but also yields a molecular-based rationale for all relative experimental findings, and leads us to conclude that the current circulating SARS-CoV-2 and all possible emergent variants carrying these mutations in the spike protein can present new challenges for mAb-based therapies and ultimately threaten the fully-protective efficacy of currently available vaccines.

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SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination

Cited by 96 publications

References 60 publications

Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

Trajectory of Growth of SARS-CoV-2 Variants in Houston, Texas, January through May 2021 Based on 12,476 Genome Sequences

In Silico Molecular-Based Rationale for SARS-CoV-2 Spike Circulating Mutations Able to Escape Bamlanivimab and Etesevimab Monoclonal Antibodies

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