Researchers have successfully engineered a new antibody that neutralizes SARS-CoV-2 (the virus that causes COVID-19) by linking two copies of the llama antibody that were proven effective in counteracting the effect of the earlier SARS virus (SARS-CoV-1). The new antibody was able to bind to the spike protein that covers the surface of SARS-CoV-2, and prevent attachment and entry into host cells.
An antibody found in llama could help prevent coronavirus (COVID-19) entry into cells, finds a new study by a team of international researchers from the University of Texas at Austin, the National Institutes of Health and Ghent University in Belgium.
The antibody in question was contrived following syndication of two copies of a special kind of antibody that worked against the earlier SARS (SARS-CoV-1) virus, which was then engineered to develop an antibody response to key protein on SARS-CoV-2, which causes COVID-19.
Preclinical trials in animals such as hamsters and non-human primates are underway, and if everything pans out, humans could be the next potential candidate for this antibody treatment.
“This is one of the first antibodies known to neutralize SARS-CoV-2,” explained Jason McLellan, associate professor of molecular biosciences at UT Austin and co-senior author, in a news release.
The immune system of camelid, such as llamas, alpacas and camels, upon detecting foreign invaders such as bacteria and virus, produces two types of antibodies: one that is strikingly identical to human antibodies and the other that is about a quarter of the size, known as single-domain antibodies or nanobodies. These single-domain antibodies, the researchers say, can be nebulized to be used in an inhaler, making them valuable therapeutic candidates.
“That makes them potentially really interesting as a drug for a respiratory pathogen because you’re delivering it right to the site of infection,” said Daniel Wrapp, a graduate student in McLellan’s lab who was involved in the study.
The initial experiment that was performed in 2016, centered on spike proteins, which allows the virus to invade host cells. The team injected the llama, then 9 months old, with stabilized spike proteins from SARS-CoV-1 and MERS-CoV. Next, they collected a blood sample, then isolated antibodies that bound to each version of the spike protein. In just a span of six weeks, one antibody, identified as “VHH-72,” was able to neutralize a pseudotyped virus – a harmless version of virus that has been genetically modified to resemble copies of the SARS-CoV-1 spike protein on its surface.
By the time the COVID-19 pandemic set out, the team tested whether the antibody “VHH-72” would be effective against SARS-Cov-2 as well. Sadly, it wasn’t. They discovered that the antibody did bind to SARS-CoV-2’s spike protein too, but rather weakly.
So in the present study, the team engineered a new antibody that binds more effectively by linking two copies of “VHH-72.” With the new antibody, they were then able to neutralize a pseudotyped virus sporting spike proteins from SARS-CoV-2. This is the first known antibody capable of neutralizing both SARS-CoV-1 and SARS-CoV-2.
“That was exciting to me because I’d been working on this for years,” said Wrapp. “But there wasn’t a big need for a coronavirus treatment then. This was just basic research. Now, this can potentially have some translational implications, too.”
The study has been published in the journal Cell.