Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore

The rapid spreading of SARS-CoV-2 variants B.1.1.7 originated from the United Kingdom and B.1.351 from South Africa has contributed to the second wave of COVID-19 cases in the respective countries and also around the world. In this study, we employed advanced biochemical and virological methodologie...

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Main Authors: Wang, Bei, Goh, Yun Shan, Prince, Tessa, Ngoh, Eve Zi Xian, Salleh, Siti Nazihah Mohd, Hor, Pei Xiang, Loh, Chiew Yee, Fong, Siew Wai, Hartley, Catherine, Tan, Seow-Yen, Young, Barnaby Edward, Leo, Yee Sin, Lye, David Chien Boon, Maurer-Stroh, Sebastian, Ng, Lisa F. P., Hiscox, Julian A., Renia, Laurent, Wang, Cheng-I
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2021
Subjects:
Online Access:https://hdl.handle.net/10356/153825
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Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-153825
record_format dspace
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Antibodies
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
spellingShingle Science::Medicine
Antibodies
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Wang, Bei
Goh, Yun Shan
Prince, Tessa
Ngoh, Eve Zi Xian
Salleh, Siti Nazihah Mohd
Hor, Pei Xiang
Loh, Chiew Yee
Fong, Siew Wai
Hartley, Catherine
Tan, Seow-Yen
Young, Barnaby Edward
Leo, Yee Sin
Lye, David Chien Boon
Maurer-Stroh, Sebastian
Ng, Lisa F. P.
Hiscox, Julian A.
Renia, Laurent
Wang, Cheng-I
Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore
description The rapid spreading of SARS-CoV-2 variants B.1.1.7 originated from the United Kingdom and B.1.351 from South Africa has contributed to the second wave of COVID-19 cases in the respective countries and also around the world. In this study, we employed advanced biochemical and virological methodologies to evaluate the impact of Spike mutations of these strains on the degree of protection afforded by humoral immune responses following natural infection of the ancestral SARS-CoV-2 strain during the early stages of the outbreak. We found that antibody-mediated neutralization activity was partially reduced for B.1.1.7 variant and significantly attenuated for the B.1.351 strain. We also found that mutations outside the receptor-binding domain (RBD) can strongly influence antibody binding and neutralization, cautioning the use of solely RBD mutations in evaluating vaccine efficacy. These findings highlight an urgent need to develop new SARS-CoV-2 vaccines that are not based exclusively on the ancestral SARS-CoV-2 Spike gene sequence.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Wang, Bei
Goh, Yun Shan
Prince, Tessa
Ngoh, Eve Zi Xian
Salleh, Siti Nazihah Mohd
Hor, Pei Xiang
Loh, Chiew Yee
Fong, Siew Wai
Hartley, Catherine
Tan, Seow-Yen
Young, Barnaby Edward
Leo, Yee Sin
Lye, David Chien Boon
Maurer-Stroh, Sebastian
Ng, Lisa F. P.
Hiscox, Julian A.
Renia, Laurent
Wang, Cheng-I
format Article
author Wang, Bei
Goh, Yun Shan
Prince, Tessa
Ngoh, Eve Zi Xian
Salleh, Siti Nazihah Mohd
Hor, Pei Xiang
Loh, Chiew Yee
Fong, Siew Wai
Hartley, Catherine
Tan, Seow-Yen
Young, Barnaby Edward
Leo, Yee Sin
Lye, David Chien Boon
Maurer-Stroh, Sebastian
Ng, Lisa F. P.
Hiscox, Julian A.
Renia, Laurent
Wang, Cheng-I
author_sort Wang, Bei
title Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore
title_short Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore
title_full Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore
title_fullStr Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore
title_full_unstemmed Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore
title_sort resistance of sars-cov-2 variants to neutralization by convalescent plasma from early covid-19 outbreak in singapore
publishDate 2021
url https://hdl.handle.net/10356/153825
_version_ 1759855268663918592
spelling sg-ntu-dr.10356-1538252023-02-28T17:10:10Z Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore Wang, Bei Goh, Yun Shan Prince, Tessa Ngoh, Eve Zi Xian Salleh, Siti Nazihah Mohd Hor, Pei Xiang Loh, Chiew Yee Fong, Siew Wai Hartley, Catherine Tan, Seow-Yen Young, Barnaby Edward Leo, Yee Sin Lye, David Chien Boon Maurer-Stroh, Sebastian Ng, Lisa F. P. Hiscox, Julian A. Renia, Laurent Wang, Cheng-I Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences Agency for Science, Technology and Research (A*STAR) Science::Medicine Antibodies Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) The rapid spreading of SARS-CoV-2 variants B.1.1.7 originated from the United Kingdom and B.1.351 from South Africa has contributed to the second wave of COVID-19 cases in the respective countries and also around the world. In this study, we employed advanced biochemical and virological methodologies to evaluate the impact of Spike mutations of these strains on the degree of protection afforded by humoral immune responses following natural infection of the ancestral SARS-CoV-2 strain during the early stages of the outbreak. We found that antibody-mediated neutralization activity was partially reduced for B.1.1.7 variant and significantly attenuated for the B.1.351 strain. We also found that mutations outside the receptor-binding domain (RBD) can strongly influence antibody binding and neutralization, cautioning the use of solely RBD mutations in evaluating vaccine efficacy. These findings highlight an urgent need to develop new SARS-CoV-2 vaccines that are not based exclusively on the ancestral SARS-CoV-2 Spike gene sequence. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) Published version This work was supported by the Biomedical Research Council (BMRC), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) (C.-I.W and L.R.) from the Agency of Science, Technology and Research (A*STAR), and National Medical Research Council (NMRC) COVID-19 Research fund (COVID-19RF-001 [L.F.P.N. and L.R.], COVID-19RF-007 [L.R., L.F.P.N., and C.-I.W.], COVID-19RF-060 [L.F.P.N. and L.R.], and COVID-19RF-004 [S.M.-S.]). This work was also partially funded by the US Food and Drug Administration Medical Countermeasures Initiative contract (75F40120C00085). The article reflects the views of the authors and does not represent the views or policies of the FDA (J.A.H.). This work was also supported by the MRC (MR/W005611/1) G2P-UK: A national virology consortium to address phenotypic consequences of SARS-CoV-2 genomic variation (J.A.H.). J.A.H. and L.F.P.N. are supported by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (award 200907). 2021-12-30T02:15:43Z 2021-12-30T02:15:43Z 2021 Journal Article Wang, B., Goh, Y. S., Prince, T., Ngoh, E. Z. X., Salleh, S. N. M., Hor, P. X., Loh, C. Y., Fong, S. W., Hartley, C., Tan, S., Young, B. E., Leo, Y. S., Lye, D. C. B., Maurer-Stroh, S., Ng, L. F. P., Hiscox, J. A., Renia, L. & Wang, C. (2021). Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore. Npj Vaccines, 6(1), 125-. https://dx.doi.org/10.1038/s41541-021-00389-2 2059-0105 https://hdl.handle.net/10356/153825 10.1038/s41541-021-00389-2 34697298 2-s2.0-85117933014 1 6 125 en ACCL/19-GAP064-R20H-H COVID-19RF-001 COVID-19RF-007 COVID-19RF-060 COVID-19RF-004 npj Vaccines © 2021 The Author(s). 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/. application/pdf