SARS-CoV-2 variants B.1.351 and B.1.1.248: Escape from therapeutic antibodies and antibodies induced by infection and vaccination

Hoffmann, Markus; Arora, Prerna; Gross, Ruediger; Seidel, Alina; Hoernich, Bojan; Hahn, Alexander S.; Krueger, Nadine; Graichen, Luise; Hofmann-Winkler, Heike; Kempf, Amy; Winkler, Martin Sebastian; Schulz, Sebastian; Jaeck, Hans-Martin; Jahrsdoerfer, Bernd; Schrezenmeier, Hubert; Mueller, Martin; Kleger, Alexander; Muench, Jan; Poehlmann, Stefan

doi:10.1101/2021.02.11.430787

Cited by 62 publications

(52 citation statements)

References 44 publications

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“…Prior to this, while many distinct spike mutations had been observed, all circulating SARS-CoV-2 lineages were defined by small numbers of mutations. All of the 501Y lineages also have significantly altered phenotypes: increased human ACE2 receptor affinity (V1, V2 and V3) [9][10][11] , increased transmissibility (V1 and V2) [12][13][14] , increased capacity to overcome prior infection and/or vaccination-induced immunity (V2 and V3) [15][16][17][18][19] and associations with increased virulence (V1) 20 . Why did the heavily mutated 501Y lineages all arise on different continents at almost the same time?…”

Section: Introductionmentioning

confidence: 99%

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

Martin

Weaver

Tegally

et al. 2021

Preprint

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The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition.

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Section: Introductionmentioning

confidence: 99%

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

Martin

Weaver

Tegally

et al. 2021

Preprint

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“…CoV-X2 is expected to be more resistant to viral escape compared to monoclonals. Indeed, we have shown that CoV-X2 binds and neutralizes mutants not recognized by its parental mAbs as well as variants of concern that recently emerged in United Kingdom 13 , South Africa 14 and Brazil 26 .…”

mentioning

confidence: 99%

Bispecific antibody neutralizes circulating SARS-CoV-2 variants, prevents escape and protects mice from disease

Gasparo¹,

Pedotti²,

Simonelli³

et al. 2021

Preprint

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SummaryNeutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19)1,2. We developed a bispecific, IgG1-like molecule based on two antibodies derived from COVID-19 convalescent donors, C121 and C1353. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, completely prevents S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 recognizes a broad panel of RBD variants and neutralizes SARS-CoV-2 and the escape mutants generated by the single monoclonals at sub-nanomolar concentrations. In a novel model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails.

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“…During the second wave of the pandemic (end of 2020/early 2021), new SARS-CoV-2 variants emerged, subsequently replacing old variants [291]. Some of these second-wave Spike mutations seem to confer partial neutralization resistance, as measured in in vitro assays with convalescent or vaccine sera [292][293][294][295][296][297]. Available potent vaccines at optimal dosing can induce multiple times higher nAb titers than convalescent sera [293,[298][299][300] and might thus have a broader window to compensate for partial Ab escape.…”

Section: Sars-cov-2 Mutates On a Low But Constant Level Yielding Mutant Variants Over Timementioning

confidence: 99%

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

Duerr¹,

Jimenez²,

Dittmann³

2021

Preprint

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SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped, positive-stranded RNA viruses with envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics delineating their distinct strategies for efficient spread.

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SARS-CoV-2 variants B.1.351 and B.1.1.248: Escape from therapeutic antibodies and antibodies induced by infection and vaccination

Cited by 62 publications

References 44 publications

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

Bispecific antibody neutralizes circulating SARS-CoV-2 variants, prevents escape and protects mice from disease

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

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