Pandemic restrictions may have been rolled back across the world, but SARS-CoV-2 continues to circulate, mutate and cause severe illness in vulnerable people as once-effective antibodies no longer bring any relief. At the same time, scientists are locked in an ongoing race against the virus to develop a vaccine that protects against more than just the known SARS-CoV-2 variants.
Now, an international research effort, led by scientists from Duke-NUS, has identified a set of exceptionally potent antibodies that offer new hope against the sarbecovirus family of coronaviruses that includes SARS-CoV-1 and SARS-CoV-2.
“We sought to address the lack of therapeutic monoclonal antibodies for treatment and prophylaxis of high-risk COVID-19 patients,” says Professor Wang Linfa from Duke-NUS’ Emerging Infectious Diseases Programme, “as all previously approved monoclonal antibodies have lost efficacy against new SARS-CoV-2 variants.”
Building on his team’s discovery in 2021 that people who had been infected with SARS-CoV-1 and were later vaccinated against SARS-CoV-2 produced powerful antibodies, Wang gathered an international team of experts to delve deeper into these immune cells.
Working with experts from the University of Melbourne, the Fred Hutchinson Cancer Research Centre in the US and the National University of Singapore, Wang and his team found that six antibodies conferred broad protection against SARS-CoV-1 and SARS-CoV-2.
“The bulk of the monoclonal antibodies we isolated were able to cross-neutralise both SARS-CoV-1 and SARS-CoV-2 viruses, which differ by more than 20 per cent from each other, suggesting that there are important and conserved epitopes that are shared between SARS-CoV-1 and SARS-CoV-2, as well as potentially amongst many members of the sarbecovirus family,” says Dr Chia Wan Ni, a former postdoctoral fellow in Wang’s lab who was the first author of this latest discovery, published in Science Advances.
Sifting further, they found that three of the six antibodies stood out as exceptionally broad and potent, proving capable of neutralising all tested SARS-related viruses at very low concentrations.
“But E7, the best monoclonal antibody we isolated, demonstrated a neutralising breadth that supersedes all reported monoclonal antibodies and continues to neutralise newly emerging Omicron variants at good potency,” says Chia.
E7’s power rests in its ability to tie up two parts of the virus’ spike protein so that the spike remains locked in its inactive form and the virus cannot shape-shift to infect cells and trigger illness.
“The E7 antibody may become a strong asset to help prevent the next outbreak caused by sarbecoviruses,” says Chia. It could be used, for example, as an anti-viral therapeutic for patients at high risk of developing severe disease or as a prophylactic for frontline workers and close contacts of confirmed cases to ringfence and restrict the spread of disease.
“Use of antibodies in both of these scenarios early in an outbreak can buy time for vaccines to be developed and will greatly reduce the mortality and disease burden,” adds Chia.
The findings’ wider implications also offer hope that the human immune system can be educated to become more resilient against coronaviruses of this family.
“We demonstrate that induction of broad sarbecovirus-neutralising antibodies is possible—it just needs the right immunogenic sequence and method of delivery,” says Wang. This could be, for example, by exposing individuals to two or three sarbecovirus vaccines that are significantly different so that the conserved neutralising flags—or epitopes—can be targeted by the immune system.
“This provides hope that the design of a universal coronavirus vaccine is achievable,” adds Wang.
These antibodies have been licensed to Singapore biotech start-up CoV Biotechnology for further development.