Cocktails of tiny llama antibodies against SARS-CoV-2, the virus that causes COVID-19, could help combat new variants of the virus, suggests a study published today in eLife.
New variants of SARS-CoV-2, including the Omicron variant, are a growing concern. The new study shows how tiny antibodies called nanobodies, produced by llamas and related animals, could potentially be combined to make treatments that are effective against these new variants and might help slow the virus’ evolution.
“The emergence of SARS-CoV-2 variants threatens current vaccines and antibodies against the virus, and urgently demands powerful new therapeutics that can resist viral escape,” says Fred Mast, Senior Research Scientist at the Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, Washington, and one of the co-first authors of the study.
To identify potential new tools against these variants, the research team from the Seattle Children’s Research Institute and the Rockefeller University in New York studied llamas immunised with the SARS-CoV-2 spike protein and catalogued hundreds of nanobodies that the animals produced. Similar to human antibodies, nanobodies help fight off infections, although they are much smaller than antibodies. Their tiny size allows them to access hard-to-reach spots on the SARS-CoV-2 virus that larger antibodies are unable to bind to.
The team specifically looked for nanobodies that attach to parts of the SARS-CoV-2 spike protein which current therapies do not target. They were then able to demonstrate how some of these nanobodies kill the SARS-CoV-2 virus, including the Delta variant, in laboratory experiments.
They also found that binding multiple copies of individual nanobodies together into a ‘multimer’ or mixing two different nanobodies into a cocktail could lead to a powerful synergy, making them even more potent and resistant to mutational escape by the virus.
Another advantage of nanobodies over more traditional antibodies is that they are remarkably stable and can tolerate high temperatures. The authors suggest this stability could allow them to be administered using a nebulizer, which creates liquid drops that can be inhaled, rather than through the intravenous infusions used to administer monoclonal antibodies.
“Such treatment would be helpful for patients in intensive care units or in lower-resource settings where intravenous infusions may not be feasible. It would also be easier to transport and store nanobodies in settings with limited access to refrigeration,” says John Aitchison, Co-Director of the Center for Global Infectious Disease Research, Seattle Children’s Research Institute, and one of the co-senior authors of the study. “We hope that our library of hundreds of new nanobodies will allow scientists to develop nanobody cocktails that could one day be used in therapies against existing and yet-to-emerge variants of SARS-CoV-2.”
The authors add that their library includes a number of nanobodies that, based on where they bind to the SARS-CoV-2 virus, could remain effective even against the new Omicron variant. They are now testing these nanobodies to determine whether they could be used in possible new treatments.
Alongside John Aitchison, the other co-senior authors of the study are Brian Chait and Michael Rout (Rockefeller University, New York). Co-first authors alongside Fred Mast are: Peter Fridy, Natalia Ketaren and Junjie Wang (Rockefeller University); Erica Jacobs (Rockefeller University and St. John’s University, Queens, New York); and Jean Paul Olivier (Seattle Children’s Research Institute, Seattle, Washington).
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To read the latest Microbiology and Infectious Disease research published in eLife, visit https://elifesciences.org/subjects/microbiology-infectious-disease.
About The Rockefeller University
The Rockefeller University is one of the world’s leading biomedical research universities and is dedicated to conducting innovative, high-quality research to improve the understanding of life for the benefit of humanity. The university’s unique approach to science has led to some of the world’s most revolutionary and transformative contributions to biology and medicine. During Rockefeller’s 120-year history, our scientists have won 26 Nobel Prizes, 25 Albert Lasker Medical Research Awards, and 20 National Medals of Science.
About Seattle Children’s Research Institute
As one of the nation’s top five pediatric research centers, Seattle Children’s Research Institute is dedicated to providing hope, care and cures to help every child live the healthiest and most fulfilling life possible. Within the research institute is the Center for Global Infectious Disease Research, whose goal is to make transformative scientific advances that lead to the prevention, treatment and cures of infectious diseases impacting children and families around the world.