Potent antibodies neutralise COVID-19, other coronaviruses

An international team of researchers have discovered exceptionally potent antibodies that can neutralise virtually all known variants of the COVID-19 virus, as well as other dangerous animal coronaviruses that could potentially cause future outbreaks. Their breakthrough has been published in the journal Science Advances.

The research team, led by Duke-NUS Medical School and including the National University of Singapore (NUS), The University of Melbourne and the Fred Hutchinson Cancer Center, isolated antibodies from the blood of a recovered SARS patient who was thereafter vaccinated against COVID-19. This combination of prior coronavirus infection and vaccination generated an extremely broad and powerful antibody response capable of stopping nearly all related coronaviruses tested.

“We sought to address the lack of therapeutic monoclonal antibodies for treatment and prophylaxis of high-risk COVID-19 patients, as all previously approved monoclonal antibodies have lost efficacy against newly emerged SARS-CoV-2 variants,” said senior author Professor Wang Linfa, from Duke-NUS’s Emerging Infectious Diseases (EID) Programme. “This work provides encouraging evidence that pan-coronavirus vaccines are possible if they can ‘educate’ the human immune system in the right way.”

The new study describes how six antibodies were obtained that could neutralise multiple coronaviruses, including SARS-CoV-2, its variants Alpha, Beta, Gamma, Delta and Omicron, the original SARS virus, and multiple other animal coronaviruses transmitted from bats and pangolins. According to first author Dr Chia Wan Ni, a former postdoctoral fellow in Wang’s lab, “Three antibodies stood out as exceptionally broad and potent, capable of neutralising all tested SARS-related viruses at very low concentrations.”

The most powerful antibody, named E7, neutralised both SARS-CoV and SARS-CoV-2 sarbecoviruses, animal sarbecoviruses and newly emerged SARS-CoV-2 variants, such as Omicron XBB.1.16. This occurred via a unique mechanism of binding that bridges two parts of the coronavirus’s spike protein that it uses to invade cells. This appears to lock the spike in an inactive conformation and block the shape-shifting process the virus requires to infect cells and cause illness.

“The neutralising potency and breadth of the E7 antibody exceeded any other SARS-related coronavirus antibodies we’ve come across,” Chia said. “It maintained activity against even the newest Omicron subvariants, while most other antibodies lose effectiveness.”

The findings thus help to unmask the weak spots of coronaviruses and provide templates for designing vaccines and drugs that work against COVID-19 variants and future coronavirus threats. According to Wang, “This work demonstrates that induction of broad sarbecovirus-neutralising antibodies is possible — it just needs the right immunogenic sequence and method of delivery. This provides hope that the design of a universal coronavirus vaccine is achievable.”

With its high potential to neutralise sarbecoviruses that emerge in the future, the E7 antibody may become a strong asset in helping to prevent the next pandemic caused by sarbecoviruses. The researchers plan to further assess the antibody’s potential as a prophylactic and therapeutic agent against existing and future coronaviruses.

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