Given the more than 200 million people that have been infected with SARS-CoV-2 globally, resulting in over 4.5 million deaths, the development of effective treatments for the infection is a global health priority. In some cases, monoclonal antibody treatments have been an effective treatment for COVID-19. But the emergence of SARS-CoV-2 variants that are partially or fully resistant to some neutralizing antibodies authorized for COVID-19 treatment bring to the forefront the need to develop cross-reactive monoclonal antibodies that are broadly effective against existing SARS-CoV-2 variants and zoonotic SARS-related viruses that may emerge in the future.
Now, a research collaboration between scientists at the Duke Human Vaccine Institute (DHVI) at Duke University and the University of North Carolina (UNC) at Chapel Hill has identified and tested an antibody that limits the severity of infections from a variety of coronaviruses, including those that cause COVID-19 as well as the original SARS illness.
This work is published in Science Translational Medicine in the article, “A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice.”
“This antibody has the potential to be a therapeutic for the current epidemic,” said co-senior author Barton Haynes, MD, director of DHVI. “It could also be available for future outbreaks, if or when other coronaviruses jump from their natural animal hosts to humans.”
The antibody was isolated by analyzing the blood from a patient who had been infected with the original SARS-CoV-1 virus, which caused the SARS outbreak in the early 2000s, and from a current COVID-19 patient. The team identified more than 1,700 monoclonal antibodies. Of the 1,700 antibodies from the two individuals, the researchers found 50 antibodies that had the ability to bind to both the original SARS virus and SARS-CoV-2.
David Martinez, PhD, a post-doctoral researcher in the Baric lab at UNC Gillings School of Global Public Health stated, on Twitter, that they found, “several antibodies that cross-reacted with SARS-CoV, SARS-CoV, bat CoV RsSHC014, RaTG13, and Pangolin spike proteins.”
Further analysis found that one of those cross-binding antibodies was especially potent and able to bind to a multitude of animal coronaviruses in addition to the two human-infecting pathogens. “This antibody binds to the coronavirus at a location that is conserved across numerous mutations and variations,” Haynes said. “As a result, it can neutralize a wide range of coronaviruses.”
Martinez tweeted that one antibody, named DH1047, neutralized alpha (B.1.1.7), beta (B.1.351), gamma (P.1), epsilon (B.1.429), iota (B.1.526), kappa (B.1.617.1), and the highly transmissible delta variant (B.1.617.2). The structure of DH1047 was solved when bound to SARS-CoV by CryoEM. He noted that the epitope bound by DH1047 is an Achilles Heel of sarbecoviruses and could be a template for a universal vaccine.
With the antibody isolated, the DHVI team turned to researchers at UNC who have expertise in animal coronaviruses. The UNC team, led by coronavirus expert Ralph Baric, PhD, epidemiology professor at UNC Gillings School of Global Public Health, tested it in mice to determine whether it could effectively block infections, or minimize the infections that occurred.
They found that it did both. When given before the animals were infected, the antibody protected mice against developing SARS, COVID-19, and its variants such as Delta, and many animal coronaviruses that have the potential to cause human pandemics.
“The findings provide a template for the rational design of universal vaccine strategies that are variant-proof and provide broad protection from known and emerging coronaviruses,” Baric said.
When given after infections, the antibody reduced severe lung symptoms compared to animals that were not treated with the antibody.
“The therapeutic activity even after mice were infected suggests that this could be a treatment deployed in the current pandemic, but also stockpiled to prevent the spread of a future outbreak or epidemic with a SARS-related virus,” said Martinez. “This antibody could be harnessed to prevent maybe SARS-CoV-3 or SARS-CoV-4.”
