SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma

Wibmer, Constantinos Kurt; Ayres, Frances; Hermanus, Tandile; Madzivhandila, Mashudu; Kgagudi, Prudence; Oosthuysen, Brent; Lambson, Bronwen E.; Oliveira, Túlio de; Vermeulen, Marion; Berg, K. van der; Rossouw, Theresa M.; Boswell, Michael T; Ueckermann, Veronica; Meiring, Susan; Gottberg, Anne von; Cohen, Cheryl; Morris, Lynn; Bhiman, Jinal N.; Moore, Penny L.

doi:10.1101/2021.01.18.427166

Cited by 403 publications

(350 citation statements)

References 53 publications

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“…Although our assays are limited to pseudotyped viruses there is an excellent correlation between pseudotyped and authentic SARS-CoV-2 neutralization assays 10 . In addition, similar results have been reported by others using vaccinee and convalescent plasmas and a variety of different pseudotype and authentic virus assays 15,31,[45][46][47][48][49] .…”

Section: Discussionsupporting

confidence: 87%

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Wang

Schmidt

Weisblum

et al. 2021

Preprint

279

313

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To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease 2019 (COVID-19) including two novel mRNA-based vaccines1,2. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known3–6. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers3,5,6. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection7,8. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

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Section: Discussionsupporting

confidence: 87%

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Wang

Schmidt

Weisblum

et al. 2021

Preprint

279

313

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“…In particular, a lot of attention has been focused on RBD mutation E484K, which has emerged in multiple independently SARS-CoV-2 lineages 63, 64 and can alter the antigenicity of the spike protein [65][66][67] . Another naturally occurring RBD mutation, K417N, which has emerged in South Africa and Brazil (B.1.351 lineage and B.1.1.28, respectively) 63, 64,68 , has recently been shown to also alter antigenicity of the spike protein 66,[69][70][71] . Consistently, we found that K417N dramatically decreased the binding of COV107-23 (clonotype 1) and COVD21-C8 (clonotype 2)…”

Section: Discussionmentioning

confidence: 99%

Sequence signatures of two IGHV3-53/3-66 public clonotypes to SARS-CoV-2 receptor binding domain

Tan

Yuan

Kuzelka

et al. 2021

Preprint

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Since the COVID-19 pandemic onset, the antibody response to SARS-CoV-2 has been extensively characterized. Antibodies to the receptor binding domain (RBD) on the spike protein are frequently encoded by IGHV3-53/3-66 with a short CDR H3. Germline-encoded sequence motifs in CDRs H1 and H2 play a major role, but whether any common motifs are present in CDR H3, which is often critical for binding specificity, have not been elucidated. Here, we identify two public clonotypes of IGHV3-53/3-66 RBD antibodies with a 9-residue CDR H3 that pair with different light chains. Distinct sequence motifs on CDR H3 are present in the two public clonotypes that appear to be related to differential light chain pairing. Additionally, we show that Y58F is a common somatic hypermutation that results in increased binding affinity of IGHV3-53/3-66 RBD antibodies with a short CDR H3. Overall, our results advance fundamental understanding of the antibody response to SARS-CoV-2.

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“…B.1.351 strains are less effectively neutralized by convalescent plasma from patients with coronavirus disease 2019 (COVID-19) and by sera from those vaccinated with several vaccines in development. [10][11][12] The decrement in neutralization can be more than 10-fold with convalescent plasma and averages 5-to 6-fold less with sera from vaccinated individuals. Fortunately, neutralization titers induced by vaccination are high, and even with a 6-fold decrease, serum can still effectively neutralize the virus.…”

mentioning

confidence: 99%

SARS-CoV-2 Viral Variants—Tackling a Moving Target

Mascola

Graham

Fauci

2021

JAMA

181

162

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In this issue of JAMA, Zhang and colleagues 1 report the emergence of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant in Southern California that accounted for 44% (37 of 85) of samples collected and studied in January 2021. The terminology of viral variation can be confusing because the media and even scientific communications often use the terms variant, strain, and lineage interchangeably. The terminology reflects the basic replication biology of RNA viruses that results in the introduction of mutations throughout the viral genome. When specific mutations, or sets of mutations, are selected through numerous rounds of viral replication, a new variant can emerge. If the sequence variation produces a virus with distinctly different phenotypic characteristics, the variant is co-termed a strain. When through genetic sequencing and phylogenetic analysis a new variant is detected as a distinct branch on a phylogenetic tree, a new lineage is born. New variants become predominant through a process of evolutionary selection that is not well understood. Once identified, several questions arise regarding the potential clinical consequences of a new variant: Is it more readily transmitted; is it more virulent or pathogenic; and can it evade immunity induced by vaccination or prior infection? For these reasons, new viral variants are studied, leading to the terms variant under investigation or variant of concern. To communicate effectively about new SARS-CoV-2 variants, a common nomenclature is needed, which like the virus, is evolving. Fortunately, the World Health Organization (WHO) is working on a systematic nomenclature that does not require a geographic reference, since viral variants can spread rapidly and globally. Currently, the terminology is overlapping, as reflected in the report by Zhang et al. 1 This new variant (CAL.20C) is termed lineage 20C/S:452R in Nextstrain nomenclature, 2 referring to the parent clade 20C and spike alteration 452R. Similarly, using a distinct PANGO nomenclature, 3 this variant derives from lineage B (B.1.429 and B.1.427). While alterations in any viral genes can have implications for pathogenesis, those arising in the spike protein that mediates viral entry into host cells and is a key target of vaccines and monoclonal antibodies are of particular interest. The new variant, identified in California and termed 20C/S:452R, has 3 amino acid changes in the spike protein, represented using the single-letter amino acid nomenclature: S13I, W152C, and L452R. To interpret this new set of alterations, it is useful to review what is known about recent variants that have become predominant in other regions of the world.

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SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma

Cited by 403 publications

References 53 publications

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Sequence signatures of two IGHV3-53/3-66 public clonotypes to SARS-CoV-2 receptor binding domain

SARS-CoV-2 Viral Variants—Tackling a Moving Target

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