SARS-CoV-2 spike variants exhibit differential infectivity and neutralization resistance to convalescent or post-vaccination sera

Kuzmina, Alona; Khalaila, Yara; Voloshin, Olga; Keren-Naus, Ayelet; Boehm-Cohen, Liora; Raviv, Yael; Shemer‐Avni, Yonat; Rosenberg, Elli; Taube, Ran

doi:10.1016/j.chom.2021.03.008

Cited by 187 publications

(212 citation statements)

References 59 publications

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“…While only minor differences were detectable for the UK, Mink, and LA variants, a substantial reduction in RBD-binding antibodies was observed for the South African variant. These findings were confirmed at the functional level by a VNT using patient-derived viral isolates, showing a significant decrease in the neutralizing capacity of sera from vaccinated or infected individuals for the South African variant, in accordance with other recently published studies [36][37][38][39] . This could provide a reasonable explanation for infection in vaccinated or convalescent individuals with the South African variant and suggests a potential reduction in the efficacy of the Pfizer BNT-162b2 vaccine from a B-cell perspective.…”

Section: Discussionsupporting

confidence: 91%

Immune response to SARS-CoV-2 variants of concern in vaccinated individuals

et al. 2021

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SARS-CoV-2 is evolving with mutations in the receptor binding domain (RBD) being of particular concern. It is important to know how much cross-protection is offered between strains following vaccination or infection. Here, we obtain serum and saliva samples from groups of vaccinated (Pfizer BNT-162b2), infected and uninfected individuals and characterize the antibody response to RBD mutant strains. Vaccinated individuals have a robust humoral response after the second dose and have high IgG antibody titers in the saliva. Antibody responses however show considerable differences in binding to RBD mutants of emerging variants of concern and substantial reduction in RBD binding and neutralization is observed against a patient-isolated South African variant. Taken together our data reinforce the importance of the second dose of Pfizer BNT-162b2 to acquire high levels of neutralizing antibodies and high antibody titers in saliva suggest that vaccinated individuals may have reduced transmission potential. Substantially reduced neutralization for the South African variant further highlights the importance of surveillance strategies to detect new variants and targeting these in future vaccines.

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Section: Discussionsupporting

confidence: 91%

Immune response to SARS-CoV-2 variants of concern in vaccinated individuals

et al. 2021

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“…1.1.7 variant N501Y, Δ69-70/N501, Δ69-70/N501+P681H behave as WT spike. The mutation E484K alone reduced sera neutralization capacity by over 5-fold [ratio NT50 mutant/NT50 WT of 0.190.21 (geometric mean  SD)], and inclusion of additional mutations (K417N and N501Y) further decreased the neutralization (0.080.05), emphasizing the role of synergic mutations on immune evasion and underscoring the need for evaluating single and combined mutations on variants (50). Other mutations at the NTD, RBD, FP, HR1, TM and CD did not significantly alter sera neutralization efficiency.…”

Section: Neutralization Assays On Spike-pseudotyped Viruses To Evaluate Synergetic Effects Of Mutationsmentioning

confidence: 99%

“…The alarm caused by the emergence of SARS-CoV-2 variants with the potential to escape host immunity acquired through infection or vaccination has been confirmed by a series of reports about lineages B.1.351 and P.1. 31, 32, 36, 50, 51 . These raise concerns on whether a reduction in vaccine efficacy could result in re-infections and delay the reduction in mortality caused by circulating SARS-CoV-2.…”

Section: Main Textmentioning

confidence: 99%

Amino acids 484 and 494 of SARS-CoV-2 spike are hotspots of immune evasion affecting antibody but not ACE2 binding

Alenquer

Ferreira

Lousa

et al. 2021

Preprint

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Understanding SARS-CoV-2 evolution and host immunity is critical to control COVID-19 pandemics. At the core is an arms-race between SARS-CoV-2 antibody and angiotensin-converting enzyme 2 (ACE2) recognition, a function of the viral protein spike. Mutations in spike impacting antibody and/or ACE2 binding are appearing worldwide, with the effect of mutation synergy still incompletely understood. We engineered 25 spike-pseudotyped lentiviruses containing individual and combined mutations, and confirmed that E484K evades antibody neutralization elicited by infection or vaccination, a capacity augmented when complemented by K417N and N501Y mutations. In silico analysis provided an explanation for E484K immune evasion. E484 frequently engages in interactions with antibodies but not with ACE2. Importantly, we identified a novel amino acid of concern, S494, which shares a similar pattern. Using the already circulating mutation S494P, we found that it reduces antibody neutralization of convalescent and post-immunization sera, particularly when combined with E484K and N501Y. Our analysis of synergic mutations provides a landscape for hotspots for immune evasion and for targets for therapies, vaccines and diagnostics.

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“…Yes (12)(13)(14)24) Yes (15,16) Found in VOCs: B. and to a lesser extent, B38 (15). E484K Yes (26) Yes (16)(17)(18) Found in VOCs: B.1.351, P1, VOC-202102/02, and VOI P.2 and P.3 Resistant to cluster 2 antibodies (16,17) Reduces neutralizing activity of human convalescent (2.5-4.2fold) and post-vaccination sera (14,18) VOC B.1.351, P.1 and P.2, which include this mutation, have shown resistance to vaccines (19)…”

Section: Sars-cov-2 Mutationsmentioning

confidence: 99%

A prospective diagnostic study to measure the accuracy of detection of SARS-CoV-2 Variants Of Concern (VOC) utilising a novel RT-PCR GENotyping algorithm in an In silico Evaluation (VOC-GENIE)

Borley¹,

Trevor²,

Richter

et al. 2021

Preprint

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Background SARS-CoV-2 variants of concern (VOCs) have been associated with higher rate of transmission, and evasion of immunisation and antibody therapeutics. Variant sequencing is widely utilized in the UK. However, only 0.5% (~650k) of the 133 million cumulative positive cases worldwide were sequenced (in GISAID) on 08 April 2021 with 97% from Europe and North America and only ~0.25% (~320k) were variant sequences. This may be due to the lack of availability, high cost, infrastructure and expert staff required for sequencing. Public health decisions based on a non-randomised sample of 0.5% of the population may be insufficiently powered, and subject to sampling bias and systematic error. In addition, sequencing is rarely available in situ in a clinically relevant timeframe and thus, is not currently compatible with diagnosis and treatment patient care pathways. Therefore, we investigated an alternative approach using polymerase chain reaction (PCR) genotyping to detect the key single nucleotide polymorphisms (SNPs) associated with increased transmission and immune evasion in SARS-CoV-2 variants. Methods We investigated the utility of SARS-CoV-2 SNP detection with a panel of PCR-genotyping assays in a large data set of 640,482 SARS-CoV-2 high quality, full length sequences using a prospective in silico trial design and explored the potential impact of rapid in situ variant testing on the COVID-19 diagnosis and treatment patient pathway. Results Five SNPs were selected by screening the published literature for a reported association with increased transmission and / or immune evasion. 344881 sequences contained one or more of the five SNPs. This algorithm of SNPs was found to be able to identify the four variants of concern (VOCs) and sequences containing the E484K and L452R escape mutations. Interpretation The in silico analysis suggest that the key mutations and variants of SARS-CoV-2 may be reliably detected using a focused algorithm of biologically relevant SNPs. This highlights the potential for rapid in situ PCR genotyping to compliment or replace sequencing or to be utilized instead of sequences in settings where sequencing is not feasible, accessible or affordable. Rapid detection of variants with in situ PCR genotyping may facilitate a more effective COVID-19 diagnosis and treatment patient pathway.

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SARS-CoV-2 spike variants exhibit differential infectivity and neutralization resistance to convalescent or post-vaccination sera

Cited by 187 publications

References 59 publications

Immune response to SARS-CoV-2 variants of concern in vaccinated individuals

Immune response to SARS-CoV-2 variants of concern in vaccinated individuals

Amino acids 484 and 494 of SARS-CoV-2 spike are hotspots of immune evasion affecting antibody but not ACE2 binding

A prospective diagnostic study to measure the accuracy of detection of SARS-CoV-2 Variants Of Concern (VOC) utilising a novel RT-PCR GENotyping algorithm in an In silico Evaluation (VOC-GENIE)

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