COVID-fighting llamas inspire 'nanobody' treatments to tackle emerging variants

By immunizing llamas with the SARS-CoV-2 spike protein, researchers isolated two tiny antibodies, or "nanobodies" that neutralized COVID-19 variants. (Alexandre Buisse/Wikimedia Commons)

The novel coronavirus that causes COVID-19 infects healthy cells in the body by binding to a region on the spike protein—but it’s a region that unfortunately can mutate, allowing the virus to escape treatments and vaccines. That’s why many scientists are still looking for weapons that can defeat the virus and any variants of it that might emerge in the future.

Enter llamas, camels and alpacas.

These mammals and other members of the camelid family naturally make tiny antibodies called nanobodies. Several research teams are developing COVID-19 antibody treatments inspired by nanobodies—and, now, one of them has preclinical evidence that the treatments may be able to neutralize emerging variants of the virus.

Scientists led by Ohio State University identified two types of nanobodies that could bypass mutations and prevent SARS-CoV-2, the virus that causes COVID-19, from entering cells. The nanobodies were able to neutralize the alpha, beta and gamma variants of the virus, the researchers reported in a study preview published online by the journal Nature.

RELATED: A COVID-19 treatment candidate that fuses tiny antibodies from llamas and alpacas shows promise

The Ohio State researchers started by immunizing llamas and transgenic mice so they would make single-chain antibodies against SARS-CoV-2. First, they immunized them with the receptor-binding domain (RBD) of the spike protein and then with the entire spike protein in the hopes of generating nanobodies with a strong ability to recognize the RBD.

They tested six different nanobodies for their ability to neutralize the virus and its variants, landing on two candidates that seemed to be able to reach a region of the RBD normal-sized antibodies would not be able to squeeze into because it’s too narrow, explained co-author Kai Xu, assistant professor of veterinary biosciences at Ohio State, in a statement. That blocked SARS-CoV-2 from invading cells.

Other academic institutions working on nanobody treatments for COVID-19 include the University of Bonn, the University of Texas at Austin and the University of California, San Francisco. Twist Bioscience reported last November that two nanobody candidates showed promise in hamster models of COVID-19.

The next step for the Ohio State-led team is to continue to isolate and study nanobodies that can neutralize COVID-19 variants in the hopes of identifying candidates for clinical development.

“Companies have already started introducing the variants of concern into the construct of booster shots of the existing vaccines,” Xu said. “But the virus is constantly mutating, and the speed of mutation may be faster than we can capture. Therefore, we need to utilize multiple mechanisms to control the virus spread.”