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.