In 2016, Dartmouth Ph.D. candidate Daniel Wrapp began working with llama antibodies to study two coronaviruses: SARS-CoV-1 and MERS-CoV. It was basic research for the McLellan Lab, which focuses on the proteins behind bacteria, fungi, parasites and viruses. Little did Wrapp know then that his basic research would have translational implications a lot sooner than expected.
Thanks to years of coronavirus research, Wrapp and his team have engineered a new antibody that binds tightly to a key protein on SARS-CoV-2, which causes COVID-19. They are already conducting preclinical studies in hamsters and, if everything goes well, the antibody treatment could potentially be available for human use in one year. Given the length of vaccine and drug development, it’s a promising timeline.
Old and new research
When the immune system of camelids, such as llamas, alpacas and camels, detect foreign invaders, the animals produce two types of antibodies: one that is strikingly similar to human antibodies, and another that is more than half the size, known as single-domain antibodies.
“This reduced size gives single-domain antibodies some interesting properties that potentially make them valuable therapeutic candidates,” Wrapp explained to Laboratory Equipment.
In initial research four years ago, the scientists focused on spike proteins, which allow the virus to both attach to and enter host cells, beginning the process of infection. Wrapp and his team injected Winter, a 9-month-old llama, with stabilized spike proteins from SARS-CoV-1 and MERS-CoV over the course of six weeks. The researchers then isolated antibodies that bound to each version of the spike protein. In cell culture, one antibody showed promise in stopping a coronavirus that relies on spike proteins from SARS-CoV-1.
In their current study, published in Cell, Wrapp and his team engineered a new antibody effective against SARS-CoV-2 by linking two copies of the llama antibody that worked against the earlier SARS virus. The single-domain antibody the researchers isolated binds to the spike protein that covers the surface of SARS-CoV-2.
“The binding of this antibody to spike is able to prevent attachment and entry, which effectively neutralizes the virus. This single-domain antibody is particularly interesting because it binds to a conserved patch on the spike protein, meaning that it is capable of neutralizing both SARS-CoV-1 and SARS-CoV-2,” Wrapp said.
According to the study authors, this is the first known antibody capable of neutralizing SARS-CoV-2. goal Their goal is to develop a treatment that can provide immediate protection from the virus, even after infection. This is especially helpful to the elderly, who do not respond to vaccines as well as younger persons, and frontline workers, who are at an increased risk of exposure.
“Vaccines have to be given a month or two before infection to provide protection. With antibody therapies, you're directly giving somebody the protective antibodies and so, immediately after treatment, they should be protected. The antibodies could also be used to treat somebody who is already sick to lessen the severity of the disease,” said Jason McLellan, professor of molecular biosciences at UT Austin and co-senior author of the paper.
Photo: Winter the llama is now 4-years-old and still living on a farm in the Belgian countryside operated by Ghent University's Vlaams Institute for Biotechnology. Wrapp said sharks are known to produce a similar class of antibodies as camelids, but “for obvious reasons, llamas are more amenable to a research environment.” Credit: Tim Coppens