Small Antibody Shown to Block Covid-19 Infection

Alpaca (Max Crawford, Unsplash)

7 Sept. 2020. Researchers in Sweden found a small-scale antibody grown in an alpaca that in lab tests blocks the SARS-CoV-2 infection mechanism. A team of micro- and cell biologists at Karolinska Institutet in Stockholm, Sweden describes its discovery in Friday’s issue of the journal Nature Communications.

Much of the biomedical research community is working on treatments for or vaccines to stop infections from SARS-CoV-2 coronaviruses responsible for Covid-19 infections, with many of those efforts developing monoclonal antibodies, engineered proteins like those produced by the immune system. A team led by Karolinska Institutet virology researchers Gerald McInerney and Benjamin Murrell is looking for an alternative source of natural antibodies that can produce the same results.

McInerney’s lab studies the interactions between viruses and cells, while Murrell researches viral dynamics using advanced genetic sequencing technology. Their work identified a small-scale antibody generated by an alpaca, a mammal native to the Andes Mountains in South America in the camelid family, related to camels and llamas. Camelids produce single-domain antibody proteins smaller in size than more complex human antibodies, thus are called nanobodies. Despite their small size, nanobodies retain the specificity and affinity properties of full-size antibodies, while being easy to produce in bacteria as well as engineered to operate as human antibodies.

The Karolinska Institutet team injected the spike glycoprotein from SARS-CoV-2 coronaviruses in an alpaca to produce nanobodies protecting against it. The coronavirus spike penetrates cells, and the protein on the spike surface binds to angiotensin coverting enzyme 2, or ACE2, receptors, which begins the infection process.  The team also injected the alpaca with an influenza protein to produce other nanobodies for comparison.

After 60 days, the researchers isolated and identified a nanobody they call Ty1, after Tyson, the name of the alpaca, generated in response to the coronavirus spike protein. In lab culture tests, the team found Ty1 antibodies, one-tenth the size of full-scale human antibodies, bind to epitopes, or binding sites on the spike protein that block the protein from connecting to ACE2 receptors, thus preventing infections from occurring. Nanobodies produced in response to the influenza protein have no effect on the coronavirus spike protein.

“Our results show that Ty1 can bind potently to the SARS-CoV-2 spike protein and neutralize the virus, with no detectable off-target activity,” says Murrell in a Karolinska Institutet statement. “We are now embarking on preclinical animal studies to investigate the neutralizing activity and therapeutic potential of Ty1 in vivo.”

The study is the first project in the CoroNAb initiative, funded by the European Union’s Horizon 2020 program, to develop therapeutic antibodies and nanobodies for Covid-19 infections. Nanobodies are also attracting commercial interest. As reported last week in Science & Enterprise, Twist Bioscience in South San Francisco is developing synthetic single-domain nanobodies against Covid-19 infections.

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