Antibody escape and global spread of SARS-CoV-2 lineage A.27

Tamara Kaleta,Guy Baele,Martin Schwemmle,Chantal Akoua‐Koffi ,Magdalena Huber,Svenja Ulferts,Robert Rutayisire,Lisa Kern ,Julius Beer,Martin Hölzer ,Georg Kochs,Mounérou Salou ,Nnaemeka Ndodo ,Lena Jaki,Etienne Simon‐Lorière ,Abdoul–Salam Ouédraogo ,Abdou Padane,Vincent Enouf,Samuel L Hong ,Gytis Dudas,Adamou Lagaré ,Sebastian Weigang,Alice Wittig,Nena Bollen,Sébastien Calvignac‐Spencer ,John Kofi Odoom,Egon A Ozer ,Alia Benkahla,Daniel Schnepf,Stefan Kröger ,Philipp Kolb,Marcus Panning,Jonas Fuchs

doi:10.1038/s41467-022-28766-y

Abstract

In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrate an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail fail to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations.

Highlights

1234567890():,; In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany
Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G
The majority of A.27 sequences deposited in GISAID between January and April 2021 originated from France (n = 263) indicating a rapid spread in France compared to Germany (Fig. 1d)

Summary

Introduction

1234567890():,; In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. As the pandemic progressed the genomic diversity of SARS-CoV-2 increased significantly and several variants of concern (VOCs) and variants of interest (VOIs) emerged These variants may be associated with higher transmissibility, can lead to more severe disease and/or significantly escape from antibody-mediated immunity, thereby reducing the effectiveness of available vaccines and treatments with mAbs[11–13]. Prominent examples are the B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants that dominated global infections in late 2020 and 2021 These variants are characterized by specific patterns of concerning S mutations: apart from the D614G substitution, lineage B.1.1.7 has the N501Y amino acid substitution associated with increased affinity to ACE214,15 and two deletions in the NTD, among other changes. This mutation was shown to enhance infectivity in vitro and decrease neutralization by sera of COVID-19 patients and vaccinees[17,18]

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