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SARS-CoV-2 B.1.617 emergence and sensitivity to vaccine-elicited antibodies

Isabella Ferreira, Rawlings Datir, Steven Kemp, Guido Papa, Partha Rakshit, Sujeet Singh, Bo Meng, Rajesh Pandey, Kalaiarasan Ponnusamy, V.S. Radhakrishnan, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The CITIID-NIHR BioResource COVID-19 Collaboration, Kei Sato, Leo James, Anurag Agrawal, View ORCID ProfileRavindra K. Gupta
doi: https://doi.org/10.1101/2021.05.08.443253
Isabella Ferreira
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
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Rawlings Datir
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
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Steven Kemp
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
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Guido Papa
3MRC – Laboratory of Molecular Biology, Cambridge, UK
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Partha Rakshit
4National Centre for Disease Control, Delhi, India
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Sujeet Singh
4National Centre for Disease Control, Delhi, India
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Bo Meng
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
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Rajesh Pandey
5CSIR Institute of Genomics and Integrative Biology, Delhi, India
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Kalaiarasan Ponnusamy
4National Centre for Disease Control, Delhi, India
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V.S. Radhakrishnan
4National Centre for Disease Control, Delhi, India
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Kei Sato
7Africa Health Research Institute, Durban, South Africa
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Leo James
3MRC – Laboratory of Molecular Biology, Cambridge, UK
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Anurag Agrawal
5CSIR Institute of Genomics and Integrative Biology, Delhi, India
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Ravindra K. Gupta
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
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  • ORCID record for Ravindra K. Gupta
  • For correspondence: rkg20@cam.ac.uk
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Abstract

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. These data demonstrate that reduced sensitivity to vaccine elicited neutralising antibodies likely contributes to vaccine breakthrough observed in India, and that polybasic cleavage site mutations potentially contribute to infectivity/transmissibility.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 18, 2021.
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SARS-CoV-2 B.1.617 emergence and sensitivity to vaccine-elicited antibodies
Isabella Ferreira, Rawlings Datir, Steven Kemp, Guido Papa, Partha Rakshit, Sujeet Singh, Bo Meng, Rajesh Pandey, Kalaiarasan Ponnusamy, V.S. Radhakrishnan, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The CITIID-NIHR BioResource COVID-19 Collaboration, Kei Sato, Leo James, Anurag Agrawal, Ravindra K. Gupta
bioRxiv 2021.05.08.443253; doi: https://doi.org/10.1101/2021.05.08.443253
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SARS-CoV-2 B.1.617 emergence and sensitivity to vaccine-elicited antibodies
Isabella Ferreira, Rawlings Datir, Steven Kemp, Guido Papa, Partha Rakshit, Sujeet Singh, Bo Meng, Rajesh Pandey, Kalaiarasan Ponnusamy, V.S. Radhakrishnan, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The CITIID-NIHR BioResource COVID-19 Collaboration, Kei Sato, Leo James, Anurag Agrawal, Ravindra K. Gupta
bioRxiv 2021.05.08.443253; doi: https://doi.org/10.1101/2021.05.08.443253

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