- The test has been validated with two COVID-19 patient cohorts in Singapore and China, achieving 99-100% specificity and 95-100% sensitivity and it is capable of differentiating antibody responses from other known human coronaviruses.
- This test would be instrumental in vaccine and therapeutic development as it is suitable for all antibody isotypes and can be used to determine antibodies in different animal species without any modification.
SINGAPORE, 24 July 2020 – As the current COVID-19 pandemic continues to adversely impact communities and economies across the world, efficiency in testing for the infection and antibodies is vital. A unique and rapid SARS-CoV-2 surrogate virus neutralisation test (sVNT), developed in Singapore, may be the much needed boost to current COVID-19 investigations to determine infection rate, herd immunity, predicted humoral protection, and vaccine efficacy during clinical trials.
According to a study published in Nature Biotechnology, the sVNT is capable of detecting the functional neutralising antibodies (NAbs) that can block the binding of the coronavirus spike protein to the angiotensin-converting enzyme 2 (ACE2) host receptor, which mimics the virus-host interaction.
The sVNT was developed by scientists from Duke-NUS Medical School, in close collaboration with National Centre for Infectious Diseases (NCID), Agency for Science, Technology and Research (A*STAR)’s Institute of Molecular and Cell Biology (IMCB) Singapore, and GenScript Biotech. The scientists in Singapore and China validated the test across two patient cohorts, with a sample size of 250 from China and 375 from Singapore, achieving 99–100 per cent specificity and 95–100 per cent sensitivity.
“The sVNT kit can detect functional NAbs in an hour and differentiate them with binding antibodies (BAbs), without the need for live virus or a biocontainment facility. It also has the ability to detect total receptor binding domain (RBD)-targeting neutralising antibodies in patient samples, in contrast to most SARS-CoV-2 antibody tests published or marketed, which are isotype-specific. This makes the sVNT accessible to the broader community for both research and clinical applications,” said Professor Wang Linfa, Director of Duke-NUS’ Emerging Infectious Diseases programme. Prof Wang is considered among the most recognised international experts on emerging zoonotic viruses and is currently serving on multiple WHO committees on COVID-19.
Infection or immunity to the virus is diagnosed by the presence of NAbs in a patient’s blood sample, which would block the RBD–ACE2 interaction. At this critical moment of the international response to the COVID-19 outbreak, there is an urgent need for a robust serological test that detects NAbs, for accurate assessment of infection prevalence and protective immunity at the individual and population level. Antibody tests, such as the conventional virus neutralization test (cVNT) and the pseudovirus-based virus neutralization test (pVNT), remain the only platforms for detecting NAbs. However, both require live viruses and cells, highly skilled operators, and days to obtain results. Other assays, such as the enzyme-linked immunosorbent assay (ELISA) detect Babs but are unable to differentiate between BAbs and NAbs.
The sVNT can also measure NAbs from different animals in a species-independent manner. It can therefore be a powerful tool to investigate the role of animals in the transmission of COVID-19 from natural reservoirs to intermediate hosts.
“It is an increasingly critical clinical question about what proportion of patients with COVID-19 develop antibodies to COVID-19, how long it lasts, and whether antibodies protect patients from reinfection. Neutralising antibody is the gold-standard serological platform to determine this. Unfortunately, the conventional virus neutralisation assay is laborious, time-consuming and requires Biosafety Level 3 for COVID-19. The sVNT developed by Prof Wang, in collaboration with the national COVID-19 PROTECT study, makes it accessible to all hospital laboratories, and is a great advance in COVID-19 serological assays,” said Associate Professor David Lye, Director, Infectious Disease Research and Training Office (IDRTO), and Senior Consultant, NCID.
Dr Sidney Yee, CEO of A*STAR’s Diagnostics Development Hub, said, “Due to the SARS outbreak in 2003, researchers in Singapore have gained important insights into that virus, which shares some similarities with SARS-Cov-2. A*STAR supported the clinical tests in this collaboration with Duke-NUS by sharing data drawn from our research experience in SARS. We are happy to have contributed to the validation of this innovative test, which will be instrumental in our fight against the global pandemic.”
“We are very pleased that Prof Wang’s work has come to fruition,” said Mr David Martz, Vice President of New Product Management, Life Sciences Group, at GenScript. “This is great news for scientists researching herd immunity and vaccine efficacy as they will now have access to this innovative research tool to accurately determine the level of neutralising antibodies in a population. We believe the test will shed new light on the current plaguing mysteries of COVID-19.”
The sVNT kit is commercialised by GenScript and offered worldwide under the brand cPass™ for research use only. GenScript has also filed for Emergency Use Authorisation with the US Food and Drug Administration and this filing is currently under review.
Reference: Chee Wah Tan1, Wan Ni Chia1, Xijian Qin, Pei Liu, Mark I-C Chen, Charles Tiu, Zhiliang Hu, Vivian Chih-Wei Chen, Barnaby E. Young, Wan Rong Sia, Yee-Joo Tan, Randy Foo, Yongxiang Yi, David C. Lye, Danielle E. Anderson and Lin-Fa Wang (2020). A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein–protein interaction. Nature Biotechnology.
Complete research paper available here.
About Duke-NUS Medical School
Duke-NUS is Singapore’s flagship graduate entry medical school, established in 2005 with a strategic, government-led partnership between two world-class institutions: Duke University School of Medicine and the National University of Singapore (NUS). Through an innovative curriculum, students at Duke-NUS are nurtured to become multi-faceted ‘Clinicians Plus’ poised to steer the healthcare and biomedical ecosystem in Singapore and beyond. A leader in ground-breaking research and translational innovation, Duke-NUS has gained international renown through its five signature research programmes and eight centres. The enduring impact of its discoveries is amplified by its successful Academic Medicine partnership with Singapore Health Services (SingHealth), Singapore’s largest healthcare group. This strategic alliance has spawned 15 Academic Clinical Programmes, which harness multi-disciplinary research and education to transform medicine and improve lives.
For more information, please visit www.duke-nus.edu.sg
About the National Centre for Infectious Diseases
The National Centre for Infectious Diseases (NCID) is a purpose-built facility designed to strengthen Singapore’s capabilities in infectious disease management and prevention. NCID houses clinical services, public health, research, training and education and community engagement functions under one overarching structure. In addition to the clinical treatment of infectious diseases and outbreak management, the expanded roles and functional units of NCID include the National Public Health and Epidemiology Unit, the National Public Health Laboratory, the Infectious Disease Research and Training Office, the Antimicrobial Resistance Coordinating Office, and the National Public Health programmes for HIV and Tuberculosis. Benchmarked to international standards and best practices for treatment and safety, NCID will better enhance Singapore’s ability to respond effectively to infectious outbreaks.
Visit www.ncid.sg for more information.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector R&D agency, spearheading economic-oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.
As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.
We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and research entities, the wider research community and industry. A*STAR’s R&D activities span biomedical sciences and physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis.
For ongoing news, visit www.a-star.edu.sg.
About GenScript Biotech Corporation
GenScript Biotech Corporation (Stock Code: 1548.HK) is a global biotechnology group. Based on its leading gene synthesis technology, GenScript has developed four major platforms including the global cell therapy platform, the biologics contract development and manufacturing organisation (CDMO) platform, the contract research organisation (CRO) platform and the industrial synthesis product platform.
GenScript was founded in New Jersey, US in 2002 and listed on the Hong Kong Stock Exchange in 2015. GenScript's business operation spans over 100 countries and regions worldwide with legal entities located in the US, Mainland China, Hong Kong, Japan, Singapore, Netherlands and Ireland. GenScript has provided premium, convenient, and reliable products and services for over 100,000 customers.
GenScript has a number of intellectual property rights and technical secrets, including more than 100 patents and over 270 patent applications. As of December 31, 2019, GenScript's products and services have been cited by 42,200 peer-reviewed journal articles worldwide.
For more information visit www.genscript.com.