Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2

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

doi:10.1038/s41598-023-49231-w

https://doi.org/10.1038/s41598-023-49231-w

Yue Gu, Bhuvaneshwari Shunmuganathan, Xinlei Qian, Rashi Gupta, Rebecca S. W. Tan, Mary Kozma, Kiren Purushotorman, Tanusya M. Murali, Nikki Y. J. Tan, Peter R. Preiser, Julien Lescar, Haziq Nasir, Jyoti Somani, Paul A. Tambyah, , Siew-Wai Fong, Siti Naqiah Amrun, Yun-Shan Goh, Matthew Zi-Rui Tay, Angeline Rouers, Zi Wei Chang, Nicholas Kim-Wah Yeo, Yi-Hao Chan, Pei Xian Hor, Chiew Yee Loh, Yuling Yang, Anthony Torres Ruesta, Vanessa Neo, Wendy Yehui Chen, Estelle Yi-Wei Goh, Alice Soh-Meoy Ong, Adeline Chiew Yen Chua, Samantha Nguee, Yong Jie Tang, Weiyi Tang, Joel Xu En Wong, Kenneth G. C. Smith, Laurent Renia, Lisa F. P. Ng, David C. Lye, Barnaby E. Young, Paul A. MacAry

09 December 2023

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., Fong, S.-W., Amrun, S. N., Goh, Y.-S., Tay, M. Z.-R., … 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). https://doi.org/10.1038/s41598-023-49231-w

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.

Attribution 4.0 International (CC BY 4.0)

This research / project is supported by the Agency of Science, Technology and Research (A*STAR) - A*ccelerate GAP-funded project
Grant Reference no. : ACCL/19-GAP064-R20H-H

This research / project is supported by the Singapore National Medical Research Council - COVID-19 Research Fund
Grant Reference no. : COVID19RF-001; COVID19RF-007; COVID19RF-0008; COVID19RF-060

This research / project is supported by the Agency of Science, Technology and Research (A*STAR) - COVID-19 Research funding
Grant Reference no. : H/20/04/g1/006

This research / project is supported by the Singapore National Medical Research Council - NA
Grant Reference no. : NA

This research / project is supported by the Ministry of Health - NA
Grant Reference no. : NA

https://oar.a-star.edu.sg/communities-collections/articles/22610

2045-2322

A*STAR Infectious Disease Labs

https://doi.org/10.1038/s41598-023-49231-w