Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

Supasa, Piyada; Zhou, Daming; Dejnirattisai, Wanwisa; Liu, C; Mentzer, Alexander J.; Ginn, H.; Zhao, Yuguang; Hme., Duyvesteyn; Nutalai, Rungtiwa; Tuekprakhon, Aekkachai; Wang, Beibei; Paesen, Guido C.; Slon-Campos, J; López-Camacho, César; Hallis, Bassam; Coombes, Naomi; Bewley, Kevin R.; Charlton, Sue; Walter, T S; Barnes, Eleanor; Dunachie, Susanna; Skelly, Donal; Lumley, Sheila F; Baker, Natalie; Shaik, Imam H.; Humphries, Holly E.; Godwin, Kerry; Gent, Nick; Sienkiewicz, Alex; Dold, Christina; Levin, Robert H.; Dong, Tao; Pollard, Andrew J.; Knight, Julian C.; Klenerman, Paul; Crook, Derrick W.; Lambe, Teresa; Clutterbuck, Elizabeth A.; Bibi, Sagida; Flaxman, Amy; Bittaye, Mustapha; Belij‐Rammerstorfer, Sandra; Gilbert, Sarah C.; Hall, '; Williams, Mark A.; Paterson, Neil G.; James, William; Carroll, Miles W.; Fry, Elizabeth E.; Mongkolsapaya, Juthathip; Ren, Jingshan; Stuart, D.I.; Screaton, Gavin

doi:10.1016/j.cell.2021.02.033

Cited by 481 publications

(602 citation statements)

References 51 publications

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“…26 Sera from recipients of the Moderna mRNA-1273 vaccine showed similar neutralising activity against VSV and lentivirus pseudoviruses expressing full-length spike protein from either B.1.1.7 or a Wuhan lineage, 42 and this finding was also seen in a live neutralisation assay. 43 However, a further live coronavirus neutralisation assay showed that sera from BNT162b2 and ChAdOx1 nCoV-19 vaccinees had a 2•0-3•3 times reduction in neutralisation activity against B.1.1.7 compared with the Victoria lineage, 44 in keeping with our findings. In the absence of a standardised method, these apparently different results with neutralising antibody assays using pseudoviruses and live virus highlight the need for caution in interpretation of viral neutralisation data.…”

Section: Discussionsupporting

confidence: 83%

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial

Emary¹,

Golubchik²,

Aley³

et al. 2021

The Lancet

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596

509

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Background A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant. Methods Volunteers (aged ≥18 years) who were enrolled in phase 2/3 vaccine efficacy studies in the UK, and who were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 or a meningococcal conjugate control (MenACWY) vaccine, provided upper airway swabs on a weekly basis and also if they developed symptoms of COVID-19 disease (a cough, a fever of 37·8°C or higher, shortness of breath, anosmia, or ageusia). Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2 and positive samples were sequenced through the COVID-19 Genomics UK consortium. Neutralising antibody responses were measured using a live-virus microneutralisation assay against the B.1.1.7 lineage and a canonical non-B.1.1.7 lineage (Victoria). The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to vaccine received. Vaccine efficacy was calculated as 1 − relative risk (ChAdOx1 nCoV-19 vs MenACWY groups) derived from a robust Poisson regression model. This study is continuing and is registered with ClinicalTrials.gov , NCT04400838 , and ISRCTN, 15281137. Findings Participants in efficacy cohorts were recruited between May 31 and Nov 13, 2020, and received booster doses between Aug 3 and Dec 30, 2020. Of 8534 participants in the primary efficacy cohort, 6636 (78%) were aged 18–55 years and 5065 (59%) were female. Between Oct 1, 2020, and Jan 14, 2021, 520 participants developed SARS-CoV-2 infection. 1466 NAAT positive nose and throat swabs were collected from these participants during the trial. Of these, 401 swabs from 311 participants were successfully sequenced. Laboratory virus neutralisation activity by vaccine-induced antibodies was lower against the B.1.1.7 variant than against the Victoria lineage (geometric mean ratio 8·9, 95% CI 7·2–11·0). Clinical vaccine efficacy against symptomatic NAAT positive infection was 70·4% (95% CI 43·6–84·5) for B.1.1.7 and 81·5% (67·9–89·4) for non-B.1.1.7 lineages. Interpretation ChAdOx1 nCoV-19 showed reduced neutralisation activity against the B.1.1.7 variant compared with a non-B.1.1.7 variant in vitro, but the vaccine showed efficacy against the B.1.1.7 variant of SARS-CoV-2. Funding UK Research and Innovation, National Institute for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

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Section: Discussionsupporting

confidence: 83%

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial

Emary¹,

Golubchik²,

Aley³

et al. 2021

The Lancet

Self Cite

596

509

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“…SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. In parallel, vaccine clinical trials held in regions with high dominance of a particular variant have demonstrated similar findings, leading to the conclusion that vaccines have greater cross-protective immunity against the B.1.1.7 compared to others, although further analysis is still needed due to small numbers in study participants [54,55]. Our analysis points to additional B cell epitope changes that may account for these results.…”

Section: Discussionsupporting

confidence: 63%

“…In general, vaccination appears to provide lower neutralizing antibody titers compared to polyclonal antibodies elicited after infection against the variants [49]. Vaccine-induced immunity provides more robust heterotypic immunity than natural infection to emerging SARS-CoV-2 variants of concern further analysis is still needed due to small numbers in study participants [54,55]. Our analysis points to additional B cell epitope changes that may account for these results.…”

Section: Discussionmentioning

confidence: 95%

Computational assessment of the spike protein antigenicity reveals diversity in B cell epitopes but stability in T cell epitopes across SARS-CoV-2 variants

Rioux

Kelvin

2021

Preprint

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Since its emergence into the human population at the end of 2019, SARS-CoV-2 has caused significant morbidity and mortality worldwide. Efforts to develop a protective vaccine against COVID-19 have yielded several vaccine platforms currently in distribution targeting the original SARS-CoV-2 spike protein sequence from the first cases of infection. In recent months, variants of SARS-CoV-2 have raised concerns that viral mutation may undermine vaccination efforts through viral escape of host immune memory acquired from infection or vaccination. We therefore used a computational approach to predict changes in spike protein antigenicity with respect to host B cell and CD8+ T cell immunity across six SARS-CoV-2 variants (D614G, B.1.1.7, B.1.351, P.1, B.1.429, and mink-related). Our epitope analysis using DiscoTope suggests possible changes in B cell epitopes in the S1 region of the spike protein across variants, in particular the B.1.1.7 and B.1.351 lineages, which may influence immunodominance. Additionally, we show that high-affinity MHC-I-binding peptides and glycosylation sites on the spike protein appear consistent between variants with the exception of an extra glycosylation site in the P.1 variant. Together, these analyses suggests T cell vaccine strategies have the most longevity before reformulation.

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“…N501Y lies in the receptor binding domain (RBD) and has been shown to enhance binding of S to its receptor ACE2 (Starr et al, 2020;Supasa et al, 2021). This mutation gives the B.1.1.7 UK variant the alternative designation 20I/501Y.V1 and has also been observed in several other lineages including the B.1.351 (501Y.V2) South African variant and the Brazilian P.1 (20J/501Y.V3) variant (Faria et al, 2021;Tegally et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Increased transmission of SARS-CoV-2 lineage B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway cells or antibody escape

Brown

Goldhill

Zhou

et al. 2021

Preprint

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Lineage B.1.1.7 (Variant of Concern 202012/01) is a new SARS-CoV-2 variant which was first sequenced in the UK in September 2020 before becoming the majority strain in the UK and spreading worldwide. The rapid spread of the B.1.1.7 variant results from increased transmissibility but the virological characteristics which underpin this advantage over other circulating strains remain unknown. Here, we demonstrate that there is no difference in viral replication between B.1.1.7 and other contemporaneous SARS-CoV-2 strains in primary human airway epithelial (HAE) cells. However, B.1.1.7 replication is disadvantaged in Vero cells potentially due to increased furin-mediated cleavage of its spike protein as a result of a P681H mutation directly adjacent to the S1/S2 cleavage site. In addition, we show that B.1.1.7 does not escape neutralisation by convalescent or post-vaccination sera. Thus, increased transmission of B.1.1.7 is not caused by increased replication, as measured on HAE cells, or escape from serological immunity.

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Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

Abstract: Highlights d Original strain convalescent and vaccine sera show reduced B.1.1.7 neutralization d N501Y enhances RBD: ACE2 binding affinity d N501Y compromises neutralization by many antibodies with public V-region IGHV3-53 d No widespread escape by B.1.1.7 was observed

Cited by 481 publications

References 51 publications

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial

Computational assessment of the spike protein antigenicity reveals diversity in B cell epitopes but stability in T cell epitopes across SARS-CoV-2 variants

Increased transmission of SARS-CoV-2 lineage B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway cells or antibody escape

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