Promising mini antibodies against COVID-19 found in llama

Neuroscientists at the National Institutes of Health have isolated a set of tiny antibodies, or “nanobodies,” against SARS-CoV-2, the virus that causes COVID-19.

Preliminary results suggest at least one of these nanobodies, called NIH-CoVnb-112, could prevent infections and detect virus particles by grabbing hold of SARS-CoV-2 spike proteins.

Where did they find these nanobodies? They were produced by a llama named Cormac.

Thomas J. “T.J.” Esparza and Dr. David L. Brody, who work in a brain imaging lab at the NIH’s National Institute of Neurological Disorders and Stroke, led the study.

“For years TJ and I had been testing out how to use nanobodies to improve brain imaging. When the pandemic broke, we thought this was a once in a lifetime, all-hands-on-deck situation and joined the fight,” Brody, who is also a professor at Uniformed Services University for the Health Sciences and the senior author of the study, said in an NIH release. “We hope that these anti-COVID-19 nanobodies may be highly effective and versatile in combating the coronavirus pandemic.”

A nanobody is a type of antibody naturally produced by the immune systems of camelids, which includes camels, llamas and alpacas. On average, these proteins are about a 10th the weight of most human antibodies.

Since the pandemic began, several researchers have produced llama nanobodies against the SARS-CoV-2 spike protein that may be effective at preventing infections. In the NIH study, Brody and Esparza used a different strategy to find nanobodies that might work especially well.

“The SARS-CoV-2 spike protein acts like a key. It does this by opening the door to infections when it binds to a protein called the angiotensin converting enzyme 2 (ACE2) receptor, found on the surface of some cells,” said Esparza, the lead author of the study. “We developed a method that would isolate nanobodies that block infections by covering the teeth of the spike protein that bind to and unlock the ACE2 receptor.”

How did they do that? The researchers immunized Cormac five times over 28 days with a purified version of the SARS-CoV-2 spike protein. After testing hundreds of nanobodies, they found that Cormac produced 13 that might be strong candidates.

One of those, called NIH-CoVnb-112, appeared to work very well. Test tube studies showed this nanobody bound to the ACE2 receptor two to 10 times stronger than nanobodies produced by other labs. Other experiments suggested the NIH nanobody stuck directly to the ACE2 receptor binding portion of the spike protein.

The team then showed the NIH-CoVnB-112 nanobody could be effective at preventing coronavirus infections.

“To mimic the SARS-CoV-2 virus, the researchers genetically mutated a harmless “pseudovirus” so that it could use the spike protein to infect cells that have human ACE2 receptors,” NIH wrote in the release. “The researchers saw that relatively low levels of the NIH-CoVnb-112 nanobodies prevented the pseudovirus from infecting these cells in petri dishes.”

In addition, the nanobody appeared to work equally well in either liquid or aerosol form, suggesting it could remain effective after inhalation.

“Although we have a lot more work ahead of us, these results represent a promising first step,” Esparza said.

The study was published last week in the journal Scientific Reports.