SANTIAGO – Do Chile’s iconic llamas hold the key to effective Covid-19 treatments? Researchers are investigating llama antibodies in the fight against the virus, but there are many limitations to using llamas, so llama-free approach with engineered yeast is also being considered. The question remains which is better.
Beloved by many, and recently hailed as the new unicorn, the llama is once again making headlines for the right reasons. Antibodies produced by llamas are unique and show original features compared to conventional antibodies. These are called nanobodies because of their smaller size, and they can function more freely. A llama nanobody is a sturdy and highly stable molecule under drastic chemical or temperature changes.
A research team from the University of Texas at Austin in collaboration with nine other researchers from the United States, Belgium, and Germany, injected Winter, a four-year-old llama with laboratory samples of coronavirus spike proteins. The antibodies produced in Winter’s blood (nanobodies) were then collected and tested on two different coronaviruses: SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome). The results were published in the international journal Cell on May 5, 2020, and indicate the llama antibodies block these viruses from entering cells by attaching to their spike proteins. This phenomenon is immunologically the neutralization of the coronaviruses.
Scientists were also able to engineer the llama antibody by merging two copies of the nanobody. The newly-formed nanobody attaches even more strongly to the virus that causes Covid-19 and is able to stop the virus from entering cells in laboratory experiments.
The authors claim the type of antibodies generated in the experimental llama to be one of the first known to fight off the novel coronavirus. Their results demonstrate that the llama antibodies targeted against coronaviruses can be produced at commercial scale for future application in epidemics. This can be achieved easily using the existing industrial setup where other biotherapeutics like monoclonal antibodies and vaccines are already being produced in the cell culture system. This suggests that more research could lead to the development of a therapy for the ongoing Covid-19 pandemic.
LLamas to the Rescue?
Any infection of the human body by invading microbes (pathogens, e.g., viruses) is like a battle of the immune system with the army (antibodies) fighting off the foreign invader (antigens) present on the surface of the pathogen. When an antigen enters the human body, the immune system produces antibodies against it. A specific group termed as neutralizing antibodies get involved that independently block viral entry into human cells.
Coronaviruses in general display the spike proteins acting as antigens. They appear as mushroom-shaped large projections on the virus surface and give them the appearance of having crowns (hence their name: corona in Latin means crown). After infection, they latch onto human cells and change their appearance to permit the virus to mingle with the host cell. Once the virus enters the host cell, it can copy itself and produce more viruses and infection spreads.
As these spike proteins are helping the virus to enter and then infect human cells, they are being targeted for the development of vaccines or treatments – e.g., by developing antibodies in llamas.
The llama – a South American relative of the camel, belonging to the Family Camelidae – is a domestic animal used by the peoples of the Andes Mountains. Larger llama populations are found in Bolivia, Peru, Argentina, Ecuador, and Colombia. In Chile, llamas are distributed in the high plane, in the regions of Tarapacá (I) and Antofagasta (II), from 2,300 to 4,000 m.
The use of llama nanobodies for virus infection research is not new. Researchers have already developed them for therapeutic applications for HIV and influenza infections. Llama antibodies can be administered as a nebulized spray. This means they can also be delivered by an inhaler directly to the lungs, which makes them particularly promising for respiratory infections such as Covid-19.
However, there are downsides to relying on llama antibodies. Not all researchers have access to llama facilities for their investigation. It is also time-consuming and expensive to generate antibodies in llamas with a shallow success rate as of now.
Or Yes to Yeast?
Yeast might be another solution. In 2018, a team of structural biologists from the Harvard Medical School, the University of California at San Francisco, and Denmark engineered a yeast alternative to llamas and successfully produced 500 million camelid antibodies. The yeast protocol can be quickly followed in a test tube in a researcher’s lab. It has a higher success rate and faster processing time than both llama immunization and previous attempts to bypass the use of camelids. This facility has been made freely available for nonprofit use.
So which is a better source for future application against Covid-19: llamas or yeast? The answer lies in the hands of an ever-expanding research network across the globe. As the earlier research with engineered yeast was reported years before the pandemic, it remains to seen whether there has since been any success in producing nanobodies directed specifically against the virus using yeast.
Dr. Mahesh Balwant Khot is working as a postdoctoral scientist at Biotechnology Centre of University of Concepcion at Concepcion campus of Chile. Dr. Mahesh is handling a FONDECYT, Goverment of Chile funded project, on biodiesel production from a newly isolated yeast obtained from Valdivian temperate forest ecosystem of southern Chile. He obtained his Ph.D. in microbiology from Shivaji University, Kolhapur and University of Pune in India.