Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2

Joseph Newman; Nazia Thakur; Thomas P. Peacock; Dagmara Bialy; Ahmed M.E. Elrefaey; Carlijn Bogaardt; Daniel L. Horton; Sammy Ho; Thivya Kankeyan; Christine Carr; Katja Hoschler; Wendy S. Barclay; Gayatri Amirthalingam; Kevin E. Brown; Bryan Charleston; Dalan Bailey

doi:10.1038/s41564-022-01163-3

Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2

Joseph Newman
, Nazia Thakur
, Thomas P. Peacock
, Dagmara Bialy
, Ahmed M.E. Elrefaey
, Carlijn Bogaardt
, Daniel L. Horton
, Sammy Ho
, Thivya Kankeyan
, Christine Carr
, Katja Hoschler
, Wendy S. Barclay
, Gayatri Amirthalingam
, Kevin E. Brown
, Bryan Charleston
, Dalan Bailey^*

^*Corresponding author for this work

Genomics

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

59 Citations (Scopus)

41 Downloads (Pure)

Abstract

SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70–89 years, vaccinated with two doses of BNT162b2 (Pfizer–BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80%), with 21.6% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.

Original language	English
Pages (from-to)	1180-1188
Number of pages	9
Journal	Nature Microbiology
Volume	7
Issue number	8
Early online date	14 Jul 2022
DOIs	https://doi.org/10.1038/s41564-022-01163-3
Publication status	Published - Aug 2022

Bibliographical note

Funding Information: We would like to acknowledge the whole of the UK Health Security Agency (formerly Public Health England) CONSENSUS team, as well as the vaccinated volunteers for their help and participation in supporting this study. This work was supported by the Medical Research Council-funded G2P-UK National Virology Consortium; G2P-UK; A National Virology Consortium to address phenotypic consequences of SARS-CoV-2 genomic variation (MR/W005611/1). J.N., N.T., D. Bialy, A.M.E.E., B.C. and D. Bailey were also funded by The Pirbright Institute’s Biotechnology and Biological Sciences Research Council institute strategic programme grant (BBS/E/I/COV07001, BBS/E/I/00007031, BBS/E/I/00007038, BBS/E/I/00007039 and BBS/E/I/00007034) with N.T. receiving studentship support from BB/T008784/1. C.B. and D.L.H. were supported by funding from the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No. 773830: One Health European Joint Programme. We would also like to acknowledge the National Institute for Communicable Diseases (NICD) and the KZN Research Innovation and Sequencing Platform (KRISP), as part of the Network for Genomic Surveillance in South Africa, for depositing the B.1.638 sequences, and the NICD, in particular D.G. Amoako and J. Everatt for providing feedback on the manuscript. The sequencing activities at the NICD were supported by: a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response; a cooperative agreement between the NICD of the National Health Laboratory Service and the UK Department of Health and Social Care, managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project.

Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Publisher Copyright: © The Author(s) 2022

Citation: Newman, J., Thakur, N., Peacock, T.P. et al. Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2. Nat Microbiol 7, 1180–1188 (2022).

DOI: https://doi.org/10.1038/s41564-022-01163-3

UN SDGs

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

SDG 3 Good Health and Well-being

Access to Document

10.1038/s41564-022-01163-3Licence: CC BY

Newman2022NeutralizingAntibodyActivityAgainst21SARS-CoV-2VariantsInOlderAdultsVaccinatedWithBNT162b2NatMicrobiolFinal published version, 2.96 MBLicence: CC BY

Cite this

Newman, J., Thakur, N., Peacock, T. P., Bialy, D., Elrefaey, A. M. E., Bogaardt, C., Horton, D. L., Ho, S., Kankeyan, T., Carr, C., Hoschler, K., Barclay, W. S., Amirthalingam, G., Brown, K. E., Charleston, B., & Bailey, D. (2022). Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2. Nature Microbiology, 7(8), 1180-1188. https://doi.org/10.1038/s41564-022-01163-3

@article{0eb0ff23bd5a47aa981ee051d3964128,

title = "Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2",

abstract = "SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70–89 years, vaccinated with two doses of BNT162b2 (Pfizer–BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80\%), with 21.6\% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.",

author = "Joseph Newman and Nazia Thakur and Peacock, \{Thomas P.\} and Dagmara Bialy and Elrefaey, \{Ahmed M.E.\} and Carlijn Bogaardt and Horton, \{Daniel L.\} and Sammy Ho and Thivya Kankeyan and Christine Carr and Katja Hoschler and Barclay, \{Wendy S.\} and Gayatri Amirthalingam and Brown, \{Kevin E.\} and Bryan Charleston and Dalan Bailey",

note = "Funding Information: We would like to acknowledge the whole of the UK Health Security Agency (formerly Public Health England) CONSENSUS team, as well as the vaccinated volunteers for their help and participation in supporting this study. This work was supported by the Medical Research Council-funded G2P-UK National Virology Consortium; G2P-UK; A National Virology Consortium to address phenotypic consequences of SARS-CoV-2 genomic variation (MR/W005611/1). J.N., N.T., D. Bialy, A.M.E.E., B.C. and D. Bailey were also funded by The Pirbright Institute{\textquoteright}s Biotechnology and Biological Sciences Research Council institute strategic programme grant (BBS/E/I/COV07001, BBS/E/I/00007031, BBS/E/I/00007038, BBS/E/I/00007039 and BBS/E/I/00007034) with N.T. receiving studentship support from BB/T008784/1. C.B. and D.L.H. were supported by funding from the European Union{\textquoteright}s Horizon 2020 Research and Innovation programme under grant agreement No. 773830: One Health European Joint Programme. We would also like to acknowledge the National Institute for Communicable Diseases (NICD) and the KZN Research Innovation and Sequencing Platform (KRISP), as part of the Network for Genomic Surveillance in South Africa, for depositing the B.1.638 sequences, and the NICD, in particular D.G. Amoako and J. Everatt for providing feedback on the manuscript. The sequencing activities at the NICD were supported by: a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response; a cooperative agreement between the NICD of the National Health Laboratory Service and the UK Department of Health and Social Care, managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article{\textquoteright}s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Publisher Copyright: {\textcopyright} The Author(s) 2022 Citation: Newman, J., Thakur, N., Peacock, T.P. et al. Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2. Nat Microbiol 7, 1180–1188 (2022). DOI: https://doi.org/10.1038/s41564-022-01163-3",

year = "2022",

month = aug,

doi = "10.1038/s41564-022-01163-3",

language = "English",

volume = "7",

pages = "1180--1188",

journal = "Nature Microbiology",

issn = "2058-5276",

publisher = "Nature Research",

number = "8",

}

Newman, J, Thakur, N, Peacock, TP, Bialy, D, Elrefaey, AME, Bogaardt, C, Horton, DL, Ho, S, Kankeyan, T, Carr, C, Hoschler, K, Barclay, WS, Amirthalingam, G , Brown, KE, Charleston, B & Bailey, D 2022, 'Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2', Nature Microbiology, vol. 7, no. 8, pp. 1180-1188. https://doi.org/10.1038/s41564-022-01163-3

TY - JOUR

T1 - Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2

AU - Newman, Joseph

AU - Thakur, Nazia

AU - Peacock, Thomas P.

AU - Bialy, Dagmara

AU - Elrefaey, Ahmed M.E.

AU - Bogaardt, Carlijn

AU - Horton, Daniel L.

AU - Ho, Sammy

AU - Kankeyan, Thivya

AU - Carr, Christine

AU - Hoschler, Katja

AU - Barclay, Wendy S.

AU - Amirthalingam, Gayatri

AU - Brown, Kevin E.

AU - Charleston, Bryan

AU - Bailey, Dalan

N1 - Funding Information: We would like to acknowledge the whole of the UK Health Security Agency (formerly Public Health England) CONSENSUS team, as well as the vaccinated volunteers for their help and participation in supporting this study. This work was supported by the Medical Research Council-funded G2P-UK National Virology Consortium; G2P-UK; A National Virology Consortium to address phenotypic consequences of SARS-CoV-2 genomic variation (MR/W005611/1). J.N., N.T., D. Bialy, A.M.E.E., B.C. and D. Bailey were also funded by The Pirbright Institute’s Biotechnology and Biological Sciences Research Council institute strategic programme grant (BBS/E/I/COV07001, BBS/E/I/00007031, BBS/E/I/00007038, BBS/E/I/00007039 and BBS/E/I/00007034) with N.T. receiving studentship support from BB/T008784/1. C.B. and D.L.H. were supported by funding from the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No. 773830: One Health European Joint Programme. We would also like to acknowledge the National Institute for Communicable Diseases (NICD) and the KZN Research Innovation and Sequencing Platform (KRISP), as part of the Network for Genomic Surveillance in South Africa, for depositing the B.1.638 sequences, and the NICD, in particular D.G. Amoako and J. Everatt for providing feedback on the manuscript. The sequencing activities at the NICD were supported by: a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response; a cooperative agreement between the NICD of the National Health Laboratory Service and the UK Department of Health and Social Care, managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Publisher Copyright: © The Author(s) 2022 Citation: Newman, J., Thakur, N., Peacock, T.P. et al. Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2. Nat Microbiol 7, 1180–1188 (2022). DOI: https://doi.org/10.1038/s41564-022-01163-3

PY - 2022/8

Y1 - 2022/8

N2 - SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70–89 years, vaccinated with two doses of BNT162b2 (Pfizer–BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80%), with 21.6% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.

AB - SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70–89 years, vaccinated with two doses of BNT162b2 (Pfizer–BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80%), with 21.6% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.

UR - https://www.scopus.com/pages/publications/85134320100

U2 - 10.1038/s41564-022-01163-3

DO - 10.1038/s41564-022-01163-3

M3 - Article

C2 - 35836002

AN - SCOPUS:85134320100

SN - 2058-5276

VL - 7

SP - 1180

EP - 1188

JO - Nature Microbiology

JF - Nature Microbiology

IS - 8

ER -

Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this