Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

OPTIC consortium; ISARIC4C consortium; Aekkachai Tuekprakhon; Rungtiwa Nutalai; Aiste Dijokaite-Guraliuc; Daming Zhou; Helen M. Ginn; Muneeswaran Selvaraj; Chang Liu; Alexander J. Mentzer; Piyada Supasa; Helen M.E. Duyvesteyn; Raksha Das; Donal Skelly; Thomas G. Ritter; Ali Amini; Sagida Bibi; Sandra Adele; Sile Ann Johnson; Bede Constantinides; Hermione Webster; Nigel Temperton; Paul Klenerman; Eleanor Barnes; Susanna J. Dunachie; Derrick Crook; Andrew J. Pollard; Teresa Lambe; Philip Goulder; Neil G. Paterson; Mark A. Williams; David R. Hall; Elizabeth E. Fry; Jiandong Huo; Juthathip Mongkolsapaya; Jingshan Ren; David I. Stuart; Gavin R. Screaton; Christopher Conlon; Alexandra Deeks; John Frater; Lisa Frending; Siobhan Gardiner; Anni Jämsén; Katie Jeffery; Tom Malone; Eloise Phillips; Lucy Rothwell; Lizzie Stafford

doi:10.1016/j.cell.2022.06.005

Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

OPTIC consortium, ISARIC4C consortium, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Aiste Dijokaite-Guraliuc, Daming Zhou, Helen M. Ginn, Muneeswaran Selvaraj, Chang Liu, Alexander J. Mentzer, Piyada Supasa, Helen M.E. Duyvesteyn, Raksha Das, Donal Skelly, Thomas G. Ritter, Ali Amini, Sagida Bibi, Sandra Adele, Sile Ann Johnson, Bede ConstantinidesHermione Webster, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Philip Goulder, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry^*, Jiandong Huo^*, Juthathip Mongkolsapaya^*, Jingshan Ren^*, David I. Stuart^*, Gavin R. Screaton^*, Christopher Conlon, Alexandra Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, Lizzie Stafford

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The Omicron lineage of SARS-CoV-2, which was first described in November 2021, spread rapidly to become globally dominant and has split into a number of sublineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sublineages, BA.4 and BA.5, which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences, and although closely related to BA.2, they contain further mutations in the receptor-binding domain of their spikes. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by the serum from individuals vaccinated with triple doses of AstraZeneca or Pfizer vaccine compared with BA.1 and BA.2. Furthermore, using the serum from BA.1 vaccine breakthrough infections, there are, likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.

Original language	English
Pages (from-to)	2422-2433.e13
Number of pages	26
Journal	Cell
Volume	185
Issue number	14
Early online date	9 Jun 2022
DOIs	https://doi.org/10.1016/j.cell.2022.06.005
Publication status	Published - 7 Jul 2022

Bibliographical note

Acknowledgments:
This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002), to D.I.S. and G.R.S. We are also grateful for support from Schmidt Futures, the Red Avenue Foundation, and the Oak Foundation. G.R.S. was supported by Wellcome. H.M.E.D. and J.R. are supported by Wellcome (101122/Z/13/Z) and D.I.S. and E.E.F. by the UKRI MRC (MR/N00065X/1). D.I.S. and G.R.S. are Jenner Investigators. This is a contribution from the UK Instruct-ERIC Centre. A.J.M. is an NIHR-supported Academic Clinical Lecturer. The convalescent sampling was supported by the Medical Research Council (grant MC_PC_19059, awarded to the ISARIC-4C Consortium, with a full contributor list available at https://isaric4c.net/about/authors/), the National Institutes for Health, the Oxford Biomedical Research Centre, and an Oxfordshire Health Services Research Committee grant to A.J.M. The Wellcome Centre for Human Genetics is supported by the Wellcome (grant 090532/Z/09/Z). The computational aspects of this research were supported by the Wellcome Core award grant number 203141/Z/16/Z and the NIHR Oxford BRC. We thank the staff of the MRC Human Immunology Unit for access to their Biacore Facility.

The Oxford Vaccine work was supported by UK Research and Innovation, the Coalition for Epidemic Preparedness Innovations, the National Institute for Health Research (NIHR), the NIHR Oxford Biomedical Research Centre, and the Thames Valley and South Midland’s NIHR Clinical Research Network. We thank the Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical team for participant sample collection and the Oxford Immunology Network Covid-19 Response T cell Consortium for laboratory support. We acknowledge the rapid sharing of Victoria, B.1.1.7, and B.1.351, which was isolated by scientists within the National Infection Service at PHE Porton Down, and the B.1.617.2 virus was kindly provided by Wendy Barclay and Thushan De Silva. We thank the Secretariat of National Surveillance, Ministry of Health, Brazil, for assistance in obtaining P.1 samples. We acknowledge Diamond Light Source for time on beamline I03 under Proposal lb27009 for COVID-19 Rapid Access. This work was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium, the UK Coronavirus Immunology Consortium (UK-CIC), and the Huo Family Foundation. E.B. and P.K. are NIHR Senior Investigators, and P.K. is funded by WT109965MA and NIH (U19 I082360). S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). D.S. is an NIHR Academic Clinical Fellow. The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the Department of Health and Social Care (DHSC), the National Institutes for Health Research (NIHR), the Medical Research Council (MRC), or Public Health England.

Keywords

VoC
SARS-CoV-2
antibody escape
Omicron
COVID-19
variant
BA.4
BA.5

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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TuekprakhonA2022AntibodyFinal published version, 6.61 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

OPTIC consortium, ISARIC4C consortium, Tuekprakhon, A., Nutalai, R., Dijokaite-Guraliuc, A., Zhou, D., Ginn, H. M., Selvaraj, M., Liu, C., Mentzer, A. J., Supasa, P., Duyvesteyn, H. M. E., Das, R., Skelly, D., Ritter, T. G., Amini, A., Bibi, S., Adele, S., Johnson, S. A., ... Stafford, L. (2022). Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum. Cell, 185(14), 2422-2433.e13. https://doi.org/10.1016/j.cell.2022.06.005

@article{e7fe2eda89c94f009913b5d7b742abf5,

title = "Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum",

abstract = "The Omicron lineage of SARS-CoV-2, which was first described in November 2021, spread rapidly to become globally dominant and has split into a number of sublineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa{\textquoteright}s Gauteng region uncovered two new sublineages, BA.4 and BA.5, which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences, and although closely related to BA.2, they contain further mutations in the receptor-binding domain of their spikes. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by the serum from individuals vaccinated with triple doses of AstraZeneca or Pfizer vaccine compared with BA.1 and BA.2. Furthermore, using the serum from BA.1 vaccine breakthrough infections, there are, likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.",

keywords = "VoC, SARS-CoV-2, antibody escape, Omicron, COVID-19, variant, BA.4, BA.5",

author = "{OPTIC consortium} and {ISARIC4C consortium} and Aekkachai Tuekprakhon and Rungtiwa Nutalai and Aiste Dijokaite-Guraliuc and Daming Zhou and Ginn, {Helen M.} and Muneeswaran Selvaraj and Chang Liu and Mentzer, {Alexander J.} and Piyada Supasa and Duyvesteyn, {Helen M.E.} and Raksha Das and Donal Skelly and Ritter, {Thomas G.} and Ali Amini and Sagida Bibi and Sandra Adele and Johnson, {Sile Ann} and Bede Constantinides and Hermione Webster and Nigel Temperton and Paul Klenerman and Eleanor Barnes and Dunachie, {Susanna J.} and Derrick Crook and Pollard, {Andrew J.} and Teresa Lambe and Philip Goulder and Paterson, {Neil G.} and Williams, {Mark A.} and Hall, {David R.} and Fry, {Elizabeth E.} and Jiandong Huo and Juthathip Mongkolsapaya and Jingshan Ren and Stuart, {David I.} and Screaton, {Gavin R.} and Christopher Conlon and Alexandra Deeks and John Frater and Lisa Frending and Siobhan Gardiner and Anni J{\"a}ms{\'e}n and Katie Jeffery and Tom Malone and Eloise Phillips and Lucy Rothwell and Lizzie Stafford and Christopher Green",

note = "Acknowledgments: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002), to D.I.S. and G.R.S. We are also grateful for support from Schmidt Futures, the Red Avenue Foundation, and the Oak Foundation. G.R.S. was supported by Wellcome. H.M.E.D. and J.R. are supported by Wellcome (101122/Z/13/Z) and D.I.S. and E.E.F. by the UKRI MRC (MR/N00065X/1). D.I.S. and G.R.S. are Jenner Investigators. This is a contribution from the UK Instruct-ERIC Centre. A.J.M. is an NIHR-supported Academic Clinical Lecturer. The convalescent sampling was supported by the Medical Research Council (grant MC_PC_19059, awarded to the ISARIC-4C Consortium, with a full contributor list available at https://isaric4c.net/about/authors/), the National Institutes for Health, the Oxford Biomedical Research Centre, and an Oxfordshire Health Services Research Committee grant to A.J.M. The Wellcome Centre for Human Genetics is supported by the Wellcome (grant 090532/Z/09/Z). The computational aspects of this research were supported by the Wellcome Core award grant number 203141/Z/16/Z and the NIHR Oxford BRC. We thank the staff of the MRC Human Immunology Unit for access to their Biacore Facility. The Oxford Vaccine work was supported by UK Research and Innovation, the Coalition for Epidemic Preparedness Innovations, the National Institute for Health Research (NIHR), the NIHR Oxford Biomedical Research Centre, and the Thames Valley and South Midland{\textquoteright}s NIHR Clinical Research Network. We thank the Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical team for participant sample collection and the Oxford Immunology Network Covid-19 Response T cell Consortium for laboratory support. We acknowledge the rapid sharing of Victoria, B.1.1.7, and B.1.351, which was isolated by scientists within the National Infection Service at PHE Porton Down, and the B.1.617.2 virus was kindly provided by Wendy Barclay and Thushan De Silva. We thank the Secretariat of National Surveillance, Ministry of Health, Brazil, for assistance in obtaining P.1 samples. We acknowledge Diamond Light Source for time on beamline I03 under Proposal lb27009 for COVID-19 Rapid Access. This work was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium, the UK Coronavirus Immunology Consortium (UK-CIC), and the Huo Family Foundation. E.B. and P.K. are NIHR Senior Investigators, and P.K. is funded by WT109965MA and NIH (U19 I082360). S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). D.S. is an NIHR Academic Clinical Fellow. The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the Department of Health and Social Care (DHSC), the National Institutes for Health Research (NIHR), the Medical Research Council (MRC), or Public Health England.",

year = "2022",

month = jul,

day = "7",

doi = "10.1016/j.cell.2022.06.005",

language = "English",

volume = "185",

pages = "2422--2433.e13",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier",

number = "14",

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OPTIC consortium, ISARIC4C consortium, Tuekprakhon, A, Nutalai, R, Dijokaite-Guraliuc, A, Zhou, D, Ginn, HM, Selvaraj, M, Liu, C, Mentzer, AJ, Supasa, P, Duyvesteyn, HME, Das, R, Skelly, D, Ritter, TG, Amini, A, Bibi, S, Adele, S, Johnson, SA, Constantinides, B, Webster, H, Temperton, N, Klenerman, P, Barnes, E, Dunachie, SJ, Crook, D, Pollard, AJ, Lambe, T, Goulder, P, Paterson, NG, Williams, MA, Hall, DR, Fry, EE, Huo, J, Mongkolsapaya, J, Ren, J, Stuart, DI, Screaton, GR, Conlon, C, Deeks, A, Frater, J, Frending, L, Gardiner, S, Jämsén, A, Jeffery, K, Malone, T, Phillips, E, Rothwell, L & Stafford, L 2022, 'Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum', Cell, vol. 185, no. 14, pp. 2422-2433.e13. https://doi.org/10.1016/j.cell.2022.06.005

TY - JOUR

T1 - Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

AU - OPTIC consortium

AU - ISARIC4C consortium

AU - Tuekprakhon, Aekkachai

AU - Nutalai, Rungtiwa

AU - Dijokaite-Guraliuc, Aiste

AU - Zhou, Daming

AU - Ginn, Helen M.

AU - Selvaraj, Muneeswaran

AU - Liu, Chang

AU - Mentzer, Alexander J.

AU - Supasa, Piyada

AU - Duyvesteyn, Helen M.E.

AU - Das, Raksha

AU - Skelly, Donal

AU - Ritter, Thomas G.

AU - Amini, Ali

AU - Bibi, Sagida

AU - Adele, Sandra

AU - Johnson, Sile Ann

AU - Constantinides, Bede

AU - Webster, Hermione

AU - Temperton, Nigel

AU - Klenerman, Paul

AU - Barnes, Eleanor

AU - Dunachie, Susanna J.

AU - Crook, Derrick

AU - Pollard, Andrew J.

AU - Lambe, Teresa

AU - Goulder, Philip

AU - Paterson, Neil G.

AU - Williams, Mark A.

AU - Hall, David R.

AU - Fry, Elizabeth E.

AU - Huo, Jiandong

AU - Mongkolsapaya, Juthathip

AU - Ren, Jingshan

AU - Stuart, David I.

AU - Screaton, Gavin R.

AU - Conlon, Christopher

AU - Deeks, Alexandra

AU - Frater, John

AU - Frending, Lisa

AU - Gardiner, Siobhan

AU - Jämsén, Anni

AU - Jeffery, Katie

AU - Malone, Tom

AU - Phillips, Eloise

AU - Rothwell, Lucy

AU - Stafford, Lizzie

AU - Green, Christopher

N1 - Acknowledgments: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002), to D.I.S. and G.R.S. We are also grateful for support from Schmidt Futures, the Red Avenue Foundation, and the Oak Foundation. G.R.S. was supported by Wellcome. H.M.E.D. and J.R. are supported by Wellcome (101122/Z/13/Z) and D.I.S. and E.E.F. by the UKRI MRC (MR/N00065X/1). D.I.S. and G.R.S. are Jenner Investigators. This is a contribution from the UK Instruct-ERIC Centre. A.J.M. is an NIHR-supported Academic Clinical Lecturer. The convalescent sampling was supported by the Medical Research Council (grant MC_PC_19059, awarded to the ISARIC-4C Consortium, with a full contributor list available at https://isaric4c.net/about/authors/), the National Institutes for Health, the Oxford Biomedical Research Centre, and an Oxfordshire Health Services Research Committee grant to A.J.M. The Wellcome Centre for Human Genetics is supported by the Wellcome (grant 090532/Z/09/Z). The computational aspects of this research were supported by the Wellcome Core award grant number 203141/Z/16/Z and the NIHR Oxford BRC. We thank the staff of the MRC Human Immunology Unit for access to their Biacore Facility. The Oxford Vaccine work was supported by UK Research and Innovation, the Coalition for Epidemic Preparedness Innovations, the National Institute for Health Research (NIHR), the NIHR Oxford Biomedical Research Centre, and the Thames Valley and South Midland’s NIHR Clinical Research Network. We thank the Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical team for participant sample collection and the Oxford Immunology Network Covid-19 Response T cell Consortium for laboratory support. We acknowledge the rapid sharing of Victoria, B.1.1.7, and B.1.351, which was isolated by scientists within the National Infection Service at PHE Porton Down, and the B.1.617.2 virus was kindly provided by Wendy Barclay and Thushan De Silva. We thank the Secretariat of National Surveillance, Ministry of Health, Brazil, for assistance in obtaining P.1 samples. We acknowledge Diamond Light Source for time on beamline I03 under Proposal lb27009 for COVID-19 Rapid Access. This work was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium, the UK Coronavirus Immunology Consortium (UK-CIC), and the Huo Family Foundation. E.B. and P.K. are NIHR Senior Investigators, and P.K. is funded by WT109965MA and NIH (U19 I082360). S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). D.S. is an NIHR Academic Clinical Fellow. The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the Department of Health and Social Care (DHSC), the National Institutes for Health Research (NIHR), the Medical Research Council (MRC), or Public Health England.

PY - 2022/7/7

Y1 - 2022/7/7

N2 - The Omicron lineage of SARS-CoV-2, which was first described in November 2021, spread rapidly to become globally dominant and has split into a number of sublineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sublineages, BA.4 and BA.5, which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences, and although closely related to BA.2, they contain further mutations in the receptor-binding domain of their spikes. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by the serum from individuals vaccinated with triple doses of AstraZeneca or Pfizer vaccine compared with BA.1 and BA.2. Furthermore, using the serum from BA.1 vaccine breakthrough infections, there are, likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.

AB - The Omicron lineage of SARS-CoV-2, which was first described in November 2021, spread rapidly to become globally dominant and has split into a number of sublineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sublineages, BA.4 and BA.5, which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences, and although closely related to BA.2, they contain further mutations in the receptor-binding domain of their spikes. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by the serum from individuals vaccinated with triple doses of AstraZeneca or Pfizer vaccine compared with BA.1 and BA.2. Furthermore, using the serum from BA.1 vaccine breakthrough infections, there are, likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.

KW - VoC

KW - SARS-CoV-2

KW - antibody escape

KW - Omicron

KW - COVID-19

KW - variant

KW - BA.4

KW - BA.5

U2 - 10.1016/j.cell.2022.06.005

DO - 10.1016/j.cell.2022.06.005

M3 - Article

SN - 0092-8674

VL - 185

SP - 2422-2433.e13

JO - Cell

JF - Cell

IS - 14

ER -

Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Abstract

Bibliographical note

Keywords

UN SDGs

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