Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2
The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we describe the development and employment of a new functional assay that measures neut...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2024
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| Online Access: | https://hdl.handle.net/10356/173702 |
| _version_ | 1824454302598430720 |
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| author | Gu, Yue Shunmuganathan, Bhuvaneshwari Qian, Xinlei Gupta, Rashi Tan, Rebecca S. W. Kozma, Mary Purushotorman, Kiren Murali, Tanusya M. Tan, Nikki Y. J. Preiser, Peter Rainer Lescar, Julien Nasir, Haziq Somani, Jyoti Tambyah, Paul A. Smith, Kenneth G. C. Renia, Laurent Ng, Lisa F. P. Lye, David C. Young, Barnaby E. MacAry, Paul A. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Gu, Yue Shunmuganathan, Bhuvaneshwari Qian, Xinlei Gupta, Rashi Tan, Rebecca S. W. Kozma, Mary Purushotorman, Kiren Murali, Tanusya M. Tan, Nikki Y. J. Preiser, Peter Rainer Lescar, Julien Nasir, Haziq Somani, Jyoti Tambyah, Paul A. Smith, Kenneth G. C. Renia, Laurent Ng, Lisa F. P. Lye, David C. Young, Barnaby E. MacAry, Paul A. |
| author_sort | Gu, Yue |
| collection | NTU |
| description | The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we describe the development and employment of a new functional assay that measures neutralizing antibodies for SARS-CoV-2 and present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced antibody responses for key variants in an Asian volunteer cohort. We also present an accurate quantitation of serological responses for SARS-CoV-2 that exploits a unique set of in-house, recombinant human monoclonal antibodies targeting the viral Spike and nucleocapsid proteins and demonstrate a reduction in neutralizing antibody titres across all groups 6 months post-vaccination. We also observe a marked reduction in the serological binding activity and neutralizing responses targeting recently newly emerged Omicron variants including XBB 1.5 and highlight a significant increase in cross-protective neutralizing antibody responses following a third dose (boost) of vaccine. These data illustrate how key virological factors such as immune escape mutations combined with host demographic factors such as age and sex of the vaccinated individual influence the strength and duration of cross-protective serological immunity for COVID-19. |
| first_indexed | 2025-02-19T03:20:09Z |
| format | Journal Article |
| id | ntu-10356/173702 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:20:09Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1737022024-02-26T15:32:33Z Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2 Gu, Yue Shunmuganathan, Bhuvaneshwari Qian, Xinlei Gupta, Rashi Tan, Rebecca S. W. Kozma, Mary Purushotorman, Kiren Murali, Tanusya M. Tan, Nikki Y. J. Preiser, Peter Rainer Lescar, Julien Nasir, Haziq Somani, Jyoti Tambyah, Paul A. Smith, Kenneth G. C. Renia, Laurent Ng, Lisa F. P. Lye, David C. Young, Barnaby E. MacAry, Paul A. School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Singapore-MIT Alliance in Research and Technology (SMART) NTU Institute of Structural Biology Medicine, Health and Life Sciences Antibodies Neutralizing The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we describe the development and employment of a new functional assay that measures neutralizing antibodies for SARS-CoV-2 and present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced antibody responses for key variants in an Asian volunteer cohort. We also present an accurate quantitation of serological responses for SARS-CoV-2 that exploits a unique set of in-house, recombinant human monoclonal antibodies targeting the viral Spike and nucleocapsid proteins and demonstrate a reduction in neutralizing antibody titres across all groups 6 months post-vaccination. We also observe a marked reduction in the serological binding activity and neutralizing responses targeting recently newly emerged Omicron variants including XBB 1.5 and highlight a significant increase in cross-protective neutralizing antibody responses following a third dose (boost) of vaccine. These data illustrate how key virological factors such as immune escape mutations combined with host demographic factors such as age and sex of the vaccinated individual influence the strength and duration of cross-protective serological immunity for COVID-19. Agency for Science, Technology and Research (A*STAR) Ministry of Health (MOH) National Medical Research Council (NMRC) Published version This work was supported by the Biomedical Research Council (BMRC), A*CRUSE (Vaccine monitoring project), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency of Science, Technology and Research (A*STAR), Singapore National Medical Research Council COVID-19 Research Fund (COVID19RF-001; COVID19RF-007; COVID19RF-0008; COVID19RF-060) and A*STAR COVID-19 Research funding (H/20/04/g1/006). This study is funded by the Singapore National Medical Research Council (R-571-000-081-213, R-711-000-058-598), Ministry of Health (R-571-000-093-114), National University of Singapore (R-571-000-081-213), and the Singapore-HUJ Alliance for Research and Enterprise (R-571-002-012-592). 2024-02-23T03:12:34Z 2024-02-23T03:12:34Z 2023 Journal Article Gu, Y., Shunmuganathan, B., Qian, X., Gupta, R., Tan, R. S. W., Kozma, M., Purushotorman, K., Murali, T. M., Tan, N. Y. J., Preiser, P. R., Lescar, J., Nasir, H., Somani, J., Tambyah, P. A., Smith, K. G. C., Renia, L., Ng, L. F. P., Lye, D. C., Young, B. E. & MacAry, P. A. (2023). Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2. Scientific Reports, 13(1), 21810-. https://dx.doi.org/10.1038/s41598-023-49231-w 2045-2322 https://hdl.handle.net/10356/173702 10.1038/s41598-023-49231-w 38071323 2-s2.0-85178884535 1 13 21810 en ACCL/19-GAP064-R20H-H COVID19RF-001 COVID19RF-007 COVID19RF-0008 COVID19RF-060 H/20/04/g1/006 R-571-000-081-213 R-711-000-058-598 R-571-000-093-114 R-571-002-012-592 Scientific Reports © 2023 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Antibodies Neutralizing Gu, Yue Shunmuganathan, Bhuvaneshwari Qian, Xinlei Gupta, Rashi Tan, Rebecca S. W. Kozma, Mary Purushotorman, Kiren Murali, Tanusya M. Tan, Nikki Y. J. Preiser, Peter Rainer Lescar, Julien Nasir, Haziq Somani, Jyoti Tambyah, Paul A. Smith, Kenneth G. C. Renia, Laurent Ng, Lisa F. P. Lye, David C. Young, Barnaby E. MacAry, Paul A. Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2 |
| title | Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2 |
| title_full | Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2 |
| title_fullStr | Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2 |
| title_full_unstemmed | Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2 |
| title_short | Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2 |
| title_sort | employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross variant neutralizing antibodies for sars cov 2 |
| topic | Medicine, Health and Life Sciences Antibodies Neutralizing |
| url | https://hdl.handle.net/10356/173702 |
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