Monoclonal antibody shows protection against COVID variants

A monoclonal antibody appears effective at neutralising the numerous variants of SARS-CoV-2, as well as related viruses in animals that could pose a threat if they were to begin spreading in people. Monoclonal antibody SC27 was identified, developed and provisionally patented by a team of US researchers led by The University of Texas at Austin, with their results published in the journal Cell Reports Medicine.

SC27 appears to work in two ways: it blocks the ACE2 binding site, which the virus uses to bind to, enter and infect cells. It also binds to a hidden or ‘cryptic’ site on the underside of the spike protein that is largely unchanged or ‘conserved’ between variants, which means SC27 can broadly recognise variants and related viruses. This is critical because if an antibody’s shape does not match enough with a virus — like two puzzle pieces that don’t quite fit — the antibody can’t effectively neutralise the virus and the virus sneaks by the body’s immune defence system.

“Other COVID-19 antibodies have been rendered ineffective as SARS-CoV-2 has evolved over the past several years,” said team leader Associate Professor Greg Ippolito, who is now based at the Texas Biomedical Research Institute. “Our new study suggests the virus is less likely to escape this treatment because SC27 targets and attaches to multiple parts of the virus’s spike protein, including sections that are not mutating as frequently.”

The researchers tested SC27 against 12 viruses, from the original SARS-CoV-2 to currently circulating variants, as well as related SARS-1 and several other coronaviruses found in bats and pangolins. Their results found the antibody was effective against all of them in a Petri dish and protected mice against both variants tested.

“This makes it broader and more effective than any other monoclonal antibody reported in scientific literature to date and the former FDA-approved cocktails,” Ippolito said, while acknowledging that SC27 still needs to be tested in human clinical trials.

Having filed a patent application for SC27, the team is now looking to collaborate with industry to further develop their monoclonal antibody treatment, which could potentially benefit immunocompromised patients who are unable to get vaccines. It also could serve as an emergency treatment during future outbreaks of new variants or coronaviruses. Next steps would include preclinical studies in larger animal models, including nonhuman primates, which are the gold standard to evaluate how complete immune systems respond to a treatment before safely moving to human clinical trials.

Notably, SC27 was found in individuals following vaccination with mRNA COVID-19 vaccines. Previously, this type of ‘class ¼’ antibody — which attaches to two distinct areas or ‘epitopes’ of the spike protein — was only detected following natural infection from SARS-1.

“This is fantastic news that vaccines can prompt the generation of these more robust and effective antibodies,” Ippolito said. “It means that future vaccine development can be tailored to generate these antibodies and have a clear metric for measuring which vaccines will be most effective.”

Image caption: Like two hands working together to form a tight grip, monoclonal antibody SC27 attaches to the SARS-CoV-2 spike protein (purple) using both of its binding domains (orange and yellow). This may explain, in part, the potency of SC27 and its ability to protect against all tested COVID-19 variants. Image credit: Greg Ippolito, PhD.