Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

Planas, Delphine; Veyer, David; Baidaliuk, Artem; Staropoli, Isabelle; Guivel‐Benhassine, Florence; Rajah, Maaran Michael; Planchais, Cyril; Porrot, Françoise; Robillard, Nicolas; Puech, Julien; Prot, Matthieu; Gallais, Floriane; Gantner, Pierre; Velay, Aurélie; Guen, J. Le; Kassis-Chikhani, Najibi; Edriss, Dhiaeddine; Bélec, Laurent; Sève, Aymeric; Péré, Hélène; Courtellemenont, Laura; Hocqueloux, Laurent; Fafi‐Kremer, Samira; Prazuck, Thiérry; Mouquet, Hugo; Bruel, Timothée; Simon‐Lorière, Etienne; Rey, F.A.; Schwartz, Olivier

doi:10.1101/2021.05.26.445838

Cited by 276 publications

(40 citation statements)

References 54 publications

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“…We demonstrate evasion of neutralising antibodies by the Delta variant live virus with sera from convalescent patients, as well as sera from individuals in the UK vaccinated with two different vaccines, one based on an adenovirus vector (ChAdOx-1), and the other mRNA (BNT162b2). Our findings on reduced susceptibility of Delta to vaccine elicited sera are similar to other reports 21,22 , including the lower GMT following two doses of ChAdOx-1 compared to BNT162b2. The vaccine sera data presented are consistent with emerging data from observational studies on vaccine efficacy (VE) in the UK, showing that VE is lower for the Delta versus the Alpha variant following both first and second doses of vaccine (PHE Technical Briefing 16).…”

Section: Discussionsupporting

confidence: 91%

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

Mlčochová¹,

Kemp²,

Dhar³

et al. 2021

Preprint

106

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The B.1.617 variant emerged in the Indian state of Maharashtra in late 2020 and has spread throughout India and to at least 40 countries. There have been fears that two key mutations seen in the receptor binding domain L452R and E484Q would have additive effects on evasion of neutralising antibodies. Here we delineate the phylogenetics of B.1.617 and spike mutation frequencies, in the context of others bearing L452R. The defining mutations in B.1.617.1 spike are L452R and E484Q in the RBD that interacts with ACE2 and is the target of neutralising antibodies. All B.1.617 viruses have the P681R mutation in the polybasic cleavage site region in spike. We report that B.1.617.1 spike bearing L452R, E484Q and P681R mediates entry into cells with slightly reduced efficiency compared to Wuhan-1. This spike confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies that is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. Furthermore we show that the P681R mutation significantly augments syncytium formation upon the B.1.617.1 spike protein, potentially contributing to increased pathogenesis observed in hamsters and infection growth rates observed in humans.

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Section: Discussionsupporting

confidence: 91%

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

Mlčochová¹,

Kemp²,

Dhar³

et al. 2021

Preprint

106

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“…The increased transmissibility and/or pathogenicity of the variants is due, at least in part, to mutations in the spike protein RBD that increase its affinity for ACE2 on target cells. Mutations in the Beta, Gamma and Delta variant spike RBDs have been shown to cause partial resistance to neutralization by the serum antibodies of vaccinated and convalescent individuals and therapeutic monoclonal antibodies [4][5][6][7][8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Comparison of Neutralizing Antibody Titers Elicited by mRNA and Adenoviral Vector Vaccine against SARS-CoV-2 Variants

Tada

Zhou

Samanovic

et al. 2021

Preprint

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The increasing prevalence of SARS-CoV-2 variants has raised concerns regarding possible decreases in vaccine efficacy. Here, neutralizing antibody titers elicited by mRNA-based and an adenoviral vector-based vaccine against variant pseudotyped viruses were compared. BNT162b2 and mRNA-1273-elicited antibodies showed modest neutralization resistance against Beta, Delta, Delta plus and Lambda variants whereas Ad26.COV2.S-elicited antibodies from a significant fraction of vaccinated individuals were of low neutralizing titer (IC50 <50). The data underscore the importance of surveillance for breakthrough infections that result in severe COVID-19 and suggest the benefit of a second immunization following Ad26.COV2.S to increase protection against the variants.

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“…Recent studies have reported resistance of B.1.617.2 to neutralization by few anti-NTD and anti-RBD mAbs, including Bamlanivimab [216,218]. Thus, B.1.617.2 spread is associated with an escape to antibodies targeting epitopes on the S protein.…”

Section: Sars-cov-2 Variantsmentioning

confidence: 99%

COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

Raman

Patel

Ranjan

2021

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic which has been a topic of major concern to global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7, B.1.351, P1 and, B.1.617., which show in-creased transmissibility and resistance towards vaccines and therapies. Importantly, the likelihood of susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response or comorbidities needs greater attention. Herein, we provide a comprehensive perspective regarding ongoing vaccine (mRNA, protein-based, viral vector based etc.) and therapeutic (mono-clonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

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Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

Cited by 276 publications

References 54 publications

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

Comparison of Neutralizing Antibody Titers Elicited by mRNA and Adenoviral Vector Vaccine against SARS-CoV-2 Variants

COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

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