A team led by emerging disease specialist Linfa Wang from Duke-NUS Medical School in Singapore identified eight SARS survivors who recently received two shots of a messenger RNA COVID-19 vaccine. In the test tube, antibodies sieved from their blood potently “neutralized” an early strain of SARS-CoV-2 as well as SARS-CoV, the virus that caused SARS, Wang and colleagues report today in The New England Journal of Medicine. The team further found these neutralizing antibodies worked well against the Alpha, Beta, and Delta variants of SARS-CoV-2 and stymied five related coronaviruses found in bats and pangolins that potentially could infect humans.
This study’s demonstration of broad spectrum immunity against sarbecoviruses—a subset of coronaviruses that includes the causes of SARS and COVID-19—is “amazing and very good news,” says Priyamvada Acharya, a structural biologist at Duke University who works on pancoronavirus vaccine research and was not involved in the new study. “This paper provides a proof of principle that a pansarbecovirus vaccine is possible.” It also marks an important step toward a long-term hope—a vaccine that works against all coronaviruses—several researchers trying to develop this dreamed of protection say.
SARS-CoV and SARS-CoV-2 are about 80% identical, and both initiate infections when their surface protein, spike, binds to the human cellular receptor known as angiotensin-converting enzyme 2 (ACE2). So Wang was surprised this year when other researchers reported that people who had recovered from SARS retained antibodies that could prevent SARS-CoV from binding to the ACE2 receptor, but didn’t seem to have any power against SARS-CoV-2. “It was always in the back of my mind that the two viruses bind to the same receptor, so why don’t [these people’s antibodies] cross neutralize?” he wondered.
The immune system’s B cells make a potpourri of antibodies against any virus, but lab tests typically measure the presence of the most abundant ones. Maybe SARS survivors harbored a population of B cells that recognized both SARS-CoV and SARS-CoV-2 but were in the minority and difficult to see, Wang reasoned. If so, he thought, a COVID-19 vaccine might bolster the population of those double-action B cells—and broaden survivors’ immunity.
To test that possibility, Wang’s team compared neutralizing antibodies from the vaccinated SARS survivors—all health care workers in Singapore—with those from SARS patients who had not received a COVID-19 vaccine. Wang’s team also analyzed antibodies in three other groups: unvaccinated people who currently had COVID-19, along with vaccinated people who had recovered from SARS-CoV-2 or had never been infected with that virus.
The vaccinated SARS survivors were the only cohort whose antibodies neutralized 10 different coronaviruses, according to a new assay Wang’s team developed that tests the antibodies’ ability to block binding between ACE2 and the receptor-binding domains (RBDs) of different spikes. (Science)