Illama-derived antibodies may block coronavirus entry into host cells
Molecules derived from the immune system of the South American mammals
illamas may block the entry of the novel coronavirus into host cells,
according to a study which could lead to a potential avenue for COVID-19
treatment. Researchers, including those from The University of Texas at
Austin in the US, have linked two copies of a special kind of antibody
molecules produced by the llama immune system to create a new type that
binds tightly to a key protein on the novel coronavirus, SARS-CoV-2.
According to the study, published in the journal Cell, this protein, called the spike protein, allows the coronavirus to break into host cells. The findings, according to the researchers, indicate that the Illama-derived antibody may block viruses with this spike protein from infecting cells cultured in the lab. "This is one of the first antibodies known to neutralise SARS-CoV-2," said study co-author Jason McLellan from UT Austin.
The scientists said they are preparing to conduct preclinical studies in animals such as hamsters or nonhuman primates, with the goal of developing a treatment that would help people soon after infection with the virus. While vaccines have to be given a month or two before infection to provide protection, the researchers said antibody therapies can achieve this immediately.
"With antibody therapies, you're directly giving somebody the protective antibodies and so, immediately after treatment, they should be protected," McLellan said. "The antibodies could also be used to treat somebody who is already sick to lessen the severity of the disease," he added. According to the researchers, this would be especially helpful for vulnerable groups such as elderly people, who mount a modest response to vaccines, meaning that their protection may be incomplete.
The scientists explained that the strategy can be made to work since the immune system of illamas produce antibodies similar to that of humans. When llamas' immune systems detect foreign invaders such as bacteria and viruses, these animals produce two types of antibodies. One of these is similar to human antibodies, and another that's only about a quarter of the size, the researchers said.
They added that the smaller ones, called single-domain antibodies or nanobodies, can be nebulised and used in an inhaler. "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, study co-author from UT Austin.
The scientists extracted the antibodies for the study from a 4-year-old illama, Winter, living on a farm in the Belgian countryside along with approximately 130 other llamas and alpacas. In 2016, when Winter was about 9 months old, the researchers were studying two earlier coronaviruses -- SARS-CoV-1 and MERS-CoV. In a process similar to humans getting shots to immunise them against a virus, the researchers injected the illama with stabilised spike proteins from the coronaviruses over the course of about six weeks.
They then collected a blood sample and isolated the antibodies bound to each version of the spike protein. According to the researchers, one of these antibodies, VHH-72, showed promise in stopping a virus with spike proteins from SARS-CoV-1 from infecting cells cultured in the lab. "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," Wrapp said.
The scientists then engineered a new antibody that showed promise for treating the current SARS-CoV-2. According to the researchers, the engineered antibody involved linking two copies of VHH-72 that bound more effectively to the novel coronavirus spike protein. They said the engineered protein can bind strongly to viruses displaying spike proteins from SARS-CoV-2 in cell cultures, adding that this is the first known antibody that neutralise both SARS-CoV-1 and SARS-CoV-2.
According to the study, published in the journal Cell, this protein, called the spike protein, allows the coronavirus to break into host cells. The findings, according to the researchers, indicate that the Illama-derived antibody may block viruses with this spike protein from infecting cells cultured in the lab. "This is one of the first antibodies known to neutralise SARS-CoV-2," said study co-author Jason McLellan from UT Austin.
The scientists said they are preparing to conduct preclinical studies in animals such as hamsters or nonhuman primates, with the goal of developing a treatment that would help people soon after infection with the virus. While vaccines have to be given a month or two before infection to provide protection, the researchers said antibody therapies can achieve this immediately.
"With antibody therapies, you're directly giving somebody the protective antibodies and so, immediately after treatment, they should be protected," McLellan said. "The antibodies could also be used to treat somebody who is already sick to lessen the severity of the disease," he added. According to the researchers, this would be especially helpful for vulnerable groups such as elderly people, who mount a modest response to vaccines, meaning that their protection may be incomplete.
The scientists explained that the strategy can be made to work since the immune system of illamas produce antibodies similar to that of humans. When llamas' immune systems detect foreign invaders such as bacteria and viruses, these animals produce two types of antibodies. One of these is similar to human antibodies, and another that's only about a quarter of the size, the researchers said.
They added that the smaller ones, called single-domain antibodies or nanobodies, can be nebulised and used in an inhaler. "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, study co-author from UT Austin.
The scientists extracted the antibodies for the study from a 4-year-old illama, Winter, living on a farm in the Belgian countryside along with approximately 130 other llamas and alpacas. In 2016, when Winter was about 9 months old, the researchers were studying two earlier coronaviruses -- SARS-CoV-1 and MERS-CoV. In a process similar to humans getting shots to immunise them against a virus, the researchers injected the illama with stabilised spike proteins from the coronaviruses over the course of about six weeks.
They then collected a blood sample and isolated the antibodies bound to each version of the spike protein. According to the researchers, one of these antibodies, VHH-72, showed promise in stopping a virus with spike proteins from SARS-CoV-1 from infecting cells cultured in the lab. "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," Wrapp said.
The scientists then engineered a new antibody that showed promise for treating the current SARS-CoV-2. According to the researchers, the engineered antibody involved linking two copies of VHH-72 that bound more effectively to the novel coronavirus spike protein. They said the engineered protein can bind strongly to viruses displaying spike proteins from SARS-CoV-2 in cell cultures, adding that this is the first known antibody that neutralise both SARS-CoV-1 and SARS-CoV-2.
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