Antibodies from llamas fight virus

Chinese scientist seeks preclinical trials to explore potential therapy

A Chinese researcher in the United Kingdom has engineered antibodies derived from llamas that are capable of neutralizing the novel coronavirus.

The antibodies could be developed and manufactured as a treatment for patients with severe COVID-19, according to Huo Jiandong, a biomedical scientist at Oxford University who co-authored the study published in the journal Nature.

"We hope that this work can be taken to preclinical trials next, to investigate their potential as a therapy," Huo told China Daily.

Earlier research has shown that small types of antibodies naturally produced by llamas known as nanobodies are effective at binding to the surface of the novel coronavirus, preventing it from entering cells and stopping infection.

Huo and his colleagues at Oxford isolated nanobodies from llama blood cells and engineered facsimiles of the molecules. They then combined these man-made nanobodies with human antibodies to form a potent "cocktail" of virus-fighting particles.

"Nanobodies are produced by the immune system of llamas, alpacas and camels," Huo said. "They are much smaller than human antibodies. In this work, we engineered a llama antibody to bind tightly to the SARS-CoV-2 spike protein, blocking it from binding to human cells."

In lab tests, the cocktail was found to be more effective at battling the virus than human or llama antibodies by themselves.

"Combinations are particularly useful since the virus has to change multiple things at the same time to escape; this is very hard for the virus to do," explained James Naismith, who is a professor of structural biology at Oxford University and director of the Rosalind Franklin Institute, which collaborated on the study.

Down the line, the engineered antibodies could be manufactured and given to patients battling COVID-19. Separate studies have shown that transfusions of serum containing human antibodies have been proven to improve patient outcomes. This serum is generally taken from ill COVID-19 patients with high levels of antibodies in their blood.

The engineered nanobodies would have an advantage over serum transfusions, as they are comparatively simple to develop and could be made on demand.

"In contrast to conventional antibodies which require mammalian cells for production, nanobodies can be manufactured quickly and cheaply using E. coli," Huo said. "Another advantage we are investigating uses the small size of the nanobodies, which means that they could be potentially formulated for administration directly to the airways of patients, using an inhaler, instead of the usual intravenous way."

The team has so far utilized two types of nanobodies taken from a lab-based library of llama antibodies, and will next screen for further types of nanobodies from Fifi, a research llama at Reading University that has been injected with novel coronavirus proteins to elicit an immune response. Isolating a number of effective molecules will allow the researchers to trial therapies that use different combinations of nanobodies against the virus.