Highlights

In brief

Antibodies from the original SARS-CoV-2 virus only partially protect against reinfection by the same strain, and may not protect against new variants with altered spike proteins.

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Are Singaporeans vulnerable to evolving viruses?

26 Dec 2022

A profile of the immune responses from Singaporean patients recovered from COVID-19 has revealed an urgent need to update vaccines against new viral variants.

The global COVID-19 vaccine rollout was a remarkable victory in a war against a pandemic that left no country untouched. While timelines for drug discovery and approval often drag on for years, the first mRNA vaccines against the SARS-CoV-2 virus were rolled out with FDA authorisation within months of testing, potentially saving millions of lives.

Unfortunately, SARS-CoV-2 remains an evolving foe in the medical arms race. “RNA-based viruses like SARS-CoV-2 constantly mutate,” explained Laurent Rénia, a Senior Fellow and Principal Investigator at the A*STAR Infectious Diseases Labs (ID Labs). “This has been shown to allow some variants of these viruses to escape the immune system.”

COVID-19 vaccines train an immune system to produce antibodies against the virus, similar to what a body would naturally do when recovering from a real infection. These antibodies often rely on binding to a specific protein on viral particles, known as the spike (S) protein, to neutralise them.

However, if certain mutations alter the S protein, they can prevent antibodies from doing their job. Experts are interested to find out whether people who recovered from the first pandemic wave might retain immune protection against emerging viral strains which, thanks to lucky (or unlucky) mutations, might have S protein shapes, unlike the original virus.

On the hunt for answers, Rénia together with Cheng-I Wang, a Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN), and their colleagues collected blood samples from 57 Singaporean patients who had experienced mild, moderate, or severe COVID-19 infections early in the pandemic. The team then analysed how well the antibodies from these samples could neutralise the original SARS-CoV-2 isolate alongside two variant strains; Alpha and Beta.

Using an S protein flow cytometry-based (SFB) assay, the researchers mixed modified cells expressing each strain’s S proteins with antibody-rich plasma extracted from patient samples. They then measured how well those antibodies bound to each type of S protein, simulating their actions against live viral counterparts.

“The SFB assay can be applied to any proteins expressed on the surface of a range of pathogens, including other viruses, bacteria and even parasites,” said Rénia, adding that they also used the technique for malaria studies.

As expected, antibody samples from study participants were most effective against the original coronavirus isolate, though not completely so. In comparison, their efficacy was partially reduced against the Alpha variant, B.1.1.7, and even more so against the Beta variant, B.1.351.

Rénia said that these results exposed a growing critical weakness in the COVID-19 vaccines originally rolled out in 2021: “These vaccines are only partially protective against reinfection by the original strain they were developed from, and sometimes not at all against variants.” This finding is particularly concerning for people with weak immune systems such as the elderly and patients on certain medications, Rénia added.

Moving forward, Rénia said the team would continue to study the emergence and immune evasion abilities of new SARS-CoV-2 variants, as they see this as an important jumping-off point for developing, designing and implementing future ’variant-proof’ COVID-19 vaccines.

The A*STAR-affiliated researchers contributing to this research are from the A*STAR Infectious Diseases Labs (ID Labs) and Singapore Immunology Network (SIgN).

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References

Wang, B., Goh, Y., Prince, T., Ngoh, E., Salleh, S., et al . Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore. NPJ Vaccines 6 (1), 125 (2021). | article

About the Researchers

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Laurent Rénia

Senior Fellow and Principal Investigator

A*STAR Infectious Diseases Labs (ID Labs)
Laurent Rénia obtained his PhD in 1991 from University Pierre et Marie Curie (now Sorbonne University) in Paris, France and did his post-doctoral New York University (1991-1992). He then returned to Paris in 1993 where he obtained a permanent position as junior research scientist at the French National Institute of Health (INSERM) in the INSERM Unit 313 at the Hopital Pitie-Salpetriere in Paris. He moved to the INSERM Unit 445 at the Institut Cochin in Paris where he started his own group in 1997. In 2001-2006, he was the Research Director at INSERM, and Co-director and Director of the Department of Immunology at the Institut Cochin. He joined SIgN in 2007, where he was Executive Director from 2013 to 2020 before becoming the founding Executive Director of the A*STAR ID Labs from 2020 to 2021. He is now Professor of infectious Diseases and director of the respiratory and Infectious Diseases Program in Lee Kong Chian School of Medicine, Nanyang Technological University, as well as a Professor in the School of Biological Sciences at NTU and a Senior Fellow and Principal Investigator at A*STAR ID Labs. He also holds an adjunct position in the French National Institute of Health (INSERM). He has published more than 330 articles and book chapters and is an Academic Editor for Infection and Immunity, PLoS ONE, Infection and Immunity, Microbial Pathogenesis, Microbial cell and Frontiers in Immunology.
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Cheng-I Wang

Principal Investigator

Singapore Immunology Network
Cheng-I Wang received a PhD degree in chemistry from Washington University and completed his postdoctoral training in the department of pharmaceutical chemistry at the University of California, San Francisco. Wang worked on drug discovery projects at biotechnology and pharmaceutical companies in the US before joining the A*STAR Singapore Immunology Network (SIgN) in 2009. As Head of the Human Monoclonal Antibody Technology Platform at SIgN, Wang works on the discovery and development of human antibodies against infection and immune disorders, using combinatorial approaches to incorporate novel functions into protein and antibody molecules.

This article was made for A*STAR Research by Wildtype Media Group