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

Kaleta et al., Research Square, doi:10.21203/
Nov 2021  
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20th treatment shown to reduce risk in May 2021
*, now known with p = 0.00029 from 20 studies, recognized in 4 countries. Efficacy is variant dependent.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments.
Anaysis of antibody escape showing variant A.27 completely escaped neutralization with LY-COV555 and partially with REGN10987. B.1.617.2 escaped these antibodies in a similar manner, suggesting that L452R facilitates the escape. Authors note that B.1.351 and P.1 escaped LY-COV555 and REGN10933, likely facilitated by the E484K mutation, suggesting that L452R and E484K lead to escape from LY-COV555 and to partial resistance to either REGN10987 or REGN10933, respectively.
Efficacy is highly variant dependent. In Vitro research suggests a lack of efficacy for omicron Haars, Liu, Pochtovyi, Sheward, VanBlargan.
Study covers bamlanivimab/etesevimab and casirivimab/imdevimab.
Kaleta et al., 2 Nov 2021, preprint, 33 authors.
This PaperBamlaniv../e..All
Antibody escape and global spread of SARS-CoV-2 lineage A.27
Tamara Kaleta, Lisa Kern, Samuel Leandro Hong, Martin Hölzer, Georg Kochs, Julius Beer, Daniel Schnepf, Martin Schwemmle, Nena Bollen, Philipp Kolb, Magdalena Huber, Svenja Ulferts, Sebastian Weigang, Gytis Dudas, Alice Wittig, Lena Jaki, Abdou Padane, Adamou Lagare, Mounerou Salou, Egon Ozer, Ndodo Nnaemeka, John Kofi Odoom, Robert Rutayisire, Alia Benkahla, Chantal Akoua-Koffi, Abdoul-Salam Ouedraogo, Etienne Simon-Loriere, Vincent Enouf, Stefan Kröger, Sébastien Calvignac-Spencer, Guy Baele, Marcus Panning, Jonas Fuchs
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 demonstrated 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 failed 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.
Author contributions JF, MH, MP, LK and TK designed the study and contributed to experiment design and data interpretation. MH, JF, SLH, NB, SC, SK and GB collected sequence and associated metadata. SLH, NB and GB performed phylogeographic analyses. JF, LK, MH, SK, SC and AW performed statistical analyses of patient metadata or analysed next-generation sequencing data. AP, AL, MS, NN, JKO, RR, AB, CAK, AO, ESL, VE and EAO provided sequencing data of SARS-CoV-2. TK, LK, JB, DS, SU, SW, GK, PK, MHU and LJ performed experiments and analysed the data. JF, LK, TK, PK, SLH and NB wrote the manuscript. JF, GD and SLH visualized the data. MP, MS and GK were involved in funding acquisition. Competing interests All authors declare to have no financial or other associations that might pose a potential or actual conflict of interest. Each of these phylogeographic analysis replicates ran for a total of 560 million iterations, respectively, with the Markov chains being sampled every 50,000th iteration, in order to reach an effective sample size (ESS) for all relevant parameters of at least 200, as determined by Tracer 1.7 68 . We used TreeAnnotator to construct maximum clade credibility (MCC) trees for each replicate. The profiles were matched with the R package dplyr, mutations with a frequency below 1% were excluded and the resulting matrix visualized with the R pheatmap package. Analysis of To identify the lineage-defining mutations, we extracted mutations that were present in 75..
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