Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

Graham, Carl; Seow, Jeffrey; Huettner, Isabella; Khan, Hataf; Kouphou, Neophytos; Acors, Sam; Winstone, Helena; Pickering, Suzanne; Galão, Rui Pedro; Dupont, Liane; Lista, María José; Jiménez-Guardeño, Jose M.; Laing, Adam; Wu, Yin; Joseph, Magdalene; Muir, Luke; Gils, Marit J. van; Ng, Weng M; Duyvesteyn, H.M.E.; Zhao, Yuguang; Bowden, Thomas A.; Shankar-Hari, Manu; Rosa, Annachiara; Cherepanov, Peter; McCoy, Laura E; Hayday, Adrian; Neil, Stuart; Malim, Michael H.; Doores, Katie J.

doi:10.1016/j.immuni.2021.03.023

Cited by 127 publications

(211 citation statements)

References 100 publications

(119 reference statements)

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“…As would be predicted, the viral variants that contain mutations in RBD amino acids in the epitopes of mAbs, including therapeutic mAbs, can show partial or complete ablation of binding. Examples of such immune escape, including loss of neutralizing mAb activity, have been shown for B.1.1.7 ( Graham et al., 2021 ), B.1.351 ( Hoffmann et al., 2021 ; Li et al., 2021 ), P.1 ( Dejnirattisai et al., 2021b ; Hoffmann et al., 2021 ), B.1.427/B.1.429 ( McCallum et al., 2021b ), and B.1.617.2 ( Planas et al., 2021 ). We expect more data on the efficacy of vaccines and antibody-based therapeutics against these and other newly emerging SARS-CoV-2 variants to become available in the coming months.…”

Section: Antibody Responses To Viral Variantsmentioning

confidence: 96%

Antibody and B cell responses to SARS-CoV-2 infection and vaccination

Röltgen

Boyd

2021

Cell Host & Microbe

118

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Antibodies, and the B cell and plasma cell populations responsible for their production, are key components of the human immune system’s response to SARS-CoV-2, which has caused the coronavirus disease 2019 (COVID-19) pandemic. Here, we review findings addressing the nature of antibody responses against SARS-CoV-2 and their role in protecting from infection or modulating COVID-19 disease severity. In just over a year, much has been learned, and replicated in independent studies, about human immune responses to this pathogen, contributing to the development of effective vaccines. Nevertheless, important questions remain about the duration and effectiveness of antibody responses, differences between immunity derived from infection compared to vaccination, the cellular basis for serological findings, and the extent to which viral variants will escape from current immunity.

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Section: Antibody Responses To Viral Variantsmentioning

confidence: 96%

Antibody and B cell responses to SARS-CoV-2 infection and vaccination

Röltgen

Boyd

2021

Cell Host & Microbe

118

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“…Studies with pseudoviruses and authentic SARS-CoV-2 containing variant substitutions suggested that adjustments to therapeutic antibody regimens might be necessary 1,2,[28][29][30] . Although our studies with variant strains in vivo suggest this conclusion likely holds for mAb monotherapy, four different mAb combinations performed well even when a virus was fully resistant to one mAb component.…”

Section: A C C E L E R a T E D A R T I C L Ementioning

confidence: 99%

In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains

Chen

Winkler

Case

et al. 2021

Nature

238

199

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This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

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“…S1c). This highlights the importance of the RBD as the major target for neutralising antibodies, whilst also underscoring the contribution of antibodies targeting regions outside of the RBD (for example the NTD of the spike protein 15,[29][30][31] ) to the neutralising antibody response, at the 5 month timepoint in this cohort. These data therefore revealed the persistence of detectable, albeit reduced, MBC specific for both spike and RBD in most people whose nAb titres against live virus had fallen below the threshold of detection.…”

Section: Sars-cov2 Spike and Rbd-specific Memory B Cells Can Persist After Loss Of Neutralising Antibodiesmentioning

confidence: 62%

“…To compare MBC frequencies in those who had maintained or lost nAb, we stained PBMC with SARS-CoV-2 spike trimer tetramers, made by pre-incubating recombinant biotinylated trimeric spike protein with fluorescently-conjugated streptavadin. 15 Dual staining with spike tetramers with two distinct fluorochromes was used to enhance the discrimination of true antigen-specific MBC (Fig.1c), as described previously. 23–25 Frequencies of antigen-specific responses were calculated within the memory fraction of B cells (CD19 + CD20 + excluding IgD + , CD38 hi and CD21 + CD27 - naïve fractions, gating strategy in Fig.S1a, as previously described 26 ).…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2-specific memory B cells can persist in the elderly despite loss of neutralising antibodies

Jeffery-Smith

Burton

Lens

et al. 2021

Preprint

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Memory B cells (MBC) can provide a recall response able to supplement waning antibodies with an affinity-matured response better able to neutralise variant viruses. We studied a cohort of vulnerable elderly care home residents and younger staff, a high proportion of whom had lost neutralising antibodies (nAb), to investigate their reserve immunity from SARS-CoV-2-specific MBC. Class-switched spike and RBD-tetramer-binding MBC with a classical phenotype persisted five months post-mild/asymptomatic SARS-CoV-2 infection, irrespective of age. Spike/RBD-specific MBC remained detectable in the majority who had lost nAb, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike/S1/RBD-specific recall was also detectable by ELISpot in some who had lost nAb, but was significantly impaired in the elderly, particularly to RBD. Our findings demonstrate persistence of SARS-CoV-2-specific MBC beyond loss of nAb, but highlight the need for careful monitoring of functional defects in RBD-specific B cell immunity in the elderly.

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Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

Cited by 127 publications

References 100 publications

Antibody and B cell responses to SARS-CoV-2 infection and vaccination

Antibody and B cell responses to SARS-CoV-2 infection and vaccination

In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains

SARS-CoV-2-specific memory B cells can persist in the elderly despite loss of neutralising antibodies

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