LLAMA ANTIBODY RESEARCH

              LLAMAS IN THE LAB

Camelids – Llamas, Alpacas, Guanacos, Vicuñas, and Camels are unique in that they have

specialized antibodies circulating in their blood. The 1989 discovery of a naturally small antibody in a camels blood has led to the development of new treatments to fight C. difficile,

hepatitis B, HIV, cancer and Alzheimer’s disease. 

Current research  being conducted by Dr. Jamshid Tanha’s antibody therapeutics group at the National Research Council Canada has revealed how antibodies derived from llamas may provide a new method for diagnosing and treating Alzheimer’s Disease.

Dr. Tanha has been involved in llama antibody therapeutics since 1997.  Scientists with the NRC,  in collaboration with the University of Calgary,  have shown how camelid antibodies recognize disease toxin proteins. This research is an important step towards developing specific ways to to treat very common and serious diseases. 

The NRC is based in Ottawa and has three integrated research and development divisions. The sectors – Emerging Technologies, Engineering, and Life Sciences, represent areas of economic

and scientific value for Canada. The Life Sciences sector develops human health technologies including vaccines, immunotherapeutics, and therapeutics that can cross the blood-brain barrier;  research involving anti-bodies derived from llamas. 

Llamas have normal antibodies like our own, as well as heavy chain antibodies from which single-domain antibodies are derived. These antibodies are ten times smaller than those  found in humans and can be more readily engineered into drug therapies.  Their small size enables them to reach places that our normal antibodies can’t. The single domain nature of these antibodies provide unique advantages which set them apart for research, diagnostic and therapeutic applications. 

The discovery of this antibody came about by chance. In 1989, students at the Free University 

of Brussels had identified what they thought were antibody fragments in a camel blood sample.

A professor at the university, Raymond Hamers, and his colleagues were intrigued, and demonstrated  that the antibodies found in camels, ( and other members of the camelid family),

consisted of two heavy chains, instead of two heavy and two light chains that make up the antibodies produced by humans.

According to Mehdi Arbabi Ghahroudi of the NCR, these unique antibodies account for 70 percent of the antibodies in a camel’s blood and 30 to 40 percent in a llama’s. As llamas are smaller, easier to work with, and more readily available than camels, companies that supply

the blood samples prefer to work with them.

HOW DO ANTIBODIES WORK? 

An antibody is a natural protein produced by white blood cells when mounting an immune response to a foreign substance (antigen) introduced into the body, such as bacteria or viruses. The antibody latches onto the antigen and either destroys it or makes it easier for white blood cells to eliminate the unwanted foreign substance. Vaccines help prepare the body, so it can

react faster and more effectively to a pathogen invasion.

ADVANTAGES OF LLAMA ANTIBODIES

The smaller size allows them to penetrate tissues, pass through the blood-brain barrier and bind epitopes that cannot be reached by conventional antibodies, making them excellent to use in immunohistochemistry.

Llama antibodies are capable of recognizing a variety of epitopes, (part of an antigen that the antibody recognizes and attaches to), located not only on the surface of a protein, but also in 

the clefts.

They have a high tolerance to extreme pH and temperature. They are more durable, capable

of withstanding temperatures of almost 200 degrees Fahrenheit.

They are easy to clone, hence a cheaper alternative for large scale production.

ALZHEIMER’S DISEASE: LLAMA ANTIBODIES DETECT CEREBRAL LESIONS

A number of research teams from around the world have been working with the NRC todevelop effective therapies and diagnostics involved with llama-derived antibody proteins.

The development of these “nanobodies” have important applications in Alzheimer’s disease.

These nanobodies are capable of crossing the blood-brain barrier, (which generally protects the brain from microbial attacks but also prevents potential therapeutic molecules from reaching it), and once in the brain can specifically mark and show amyloid plaques and neurofibrillary tangles, the two types of lesions that characterize Alzheimer’s disease. 

Amyloid beta peptide, naturally present in the brain, builds up over the years as a result of genetic and environmental factors until it forms amyloid plaques.  This build-up is toxic for nerve cells and leads to a loss of neuronal structure and to what is known as neurofibrillary tangles, which in turn results in cell death.

“The blood-brain barrier rejects many things, including drugs”, says Dr. Tanha. “We’ve developed single-domain antibodies that are ‘transcytotic’, which means they can get across

the cells of the brain’s protective layer.” 

Early detection of Alzheimer’s can lead to better treatment and better outcomes for peoplewith this brain disease. The scientists involved in this collaborative project  are working on 

MRI techniques to detect the lesions associated with Alzheimer’s disease. At present they are

using two-photon microscopy to detect signs of the disease in vivo in mice.  Human trials using llama antibodies in Alzheimer’s patients are predicted to get underway in the next few years.

With greater interest and involvement from the pharmaceutical and biotechnology companies

llama-derived antibodies may soon become a standard therapy in testing, diagnosing, and treating diseases in humans as well as animals. Dow Agro Sciences has licensed llama antibody technology for animal health and food safety applications. Texas Biomedical Research Institute is developing tests using llama-derived antibodies to detect hemorrhagic fever viruses, including Ebola and Marburg. 

EVOLUTIONARY ADVANTAGES OF THE CAMELID FAMILY ARE PROVING TO BE OUR NEW LINE OF DEFENCE – IN SO MANY WAYS

Llama antibodies can act as sensors to warn of dangerous microbes and chemicals in the event of a biological attack. Researchers at the U.S. Naval Research Laboratory in Washington were able to successfully engineer llama-derived antibodies that have the ability to detect cholera toxin, a smallpox virus surrogate, and ricin in the environment. Scientists at Southwest Foundation for Biomedical Research have developed tests using llama-derived antibody proteins to detect seven different types of  botulinum neurotoxins. Botulinum neurotoxins are about 100 billion times more toxic than cyanide, and should there be a bioterror threat, the ability to detect these toxins in our water supply or food-chain is critically important.  

CUSTOM ANTIBODIES

About a dozen Science and Technology companies are now offering single-domain antibody

services.  Using bioengineering techniques, the antibody genes from llama and alpaca blood samples are cloned. These “libraries” provide researchers with naive and immunized camelid antibodies from which they can conduct their research and develop new techniques to safeguard human health, target certain diseases, and discover new cures.

Most of us know llamas as providers of luxurious fleece, or for their athletic abilities as a

pack-animal, as therapy animals, companions, as well as guardians of livestock.   Their important contribution to science is yet another reason to appreciate our camelid friends.

3.5 million years ago, during a global warming spell, giant camels lived in the boreal forest of Ellesmere Island. These large, shaggy coated camels, with their iconic humps, (which store fat), were able to survive the long, cold Arctic winters.

Ellesmere Island, Nunavut, is located in the Canadian Arctic. This is where the remains of         a giant ancient camel were uncovered – the first camel ever found in the High Arctic. This amazing discovery was made by Dr. Natalia Rybczynski, a paleontologist at the Canadian Museum of Nature.  

An analysis of protein found in the bones suggest that the evolutionary history of modern camels can be traced back to  the lineage of these giants. Most closely related are the dromedaries, (camels with one hump). The camels that we are familiar with in current times share evolutionary characteristics that enabled the giant camels of Ellesmere Island to thrive in the High Arctic. Dr. Rybczynski suggests that perhaps some specializations seen in modern camels, such as their wide flat feet, large eyes, and humps for fat, are adaptations derived from living in a polar environment,

Previous to the discovery on Ellesmere Island, the most northerly evidence of camels was in the Yukon, over 2,000 kilometers away. Mike Buckley at the University of Manchester in England was able to determine through “collagen fingerprinting” that the Ellesmere camel was from the same line as the ancient camel remains unearthed years ago in the Yukon.

Dr.John Goose at Dalhousie University determined an accurate age of the site on Ellesmere by using a sophisticated technique that involves dating the sands found associated with the bone fragments. This is significant, as it corresponds to a time period when the Earth was two to three degrees warmer than today. The Arctic was 14 degrees C to 22 degrees C warmer.

The Ellesmere Camel inhabited the High Arctic during the mid-Pliocene warm period when the area was forested and the broad channels of the western Canadian Arctic Archipelago were filled with sediment, forming a wide land bridge. Animal species moved freely across this open land connection, allowing the camel line of Camelidae to migrate into Asia to continue it’s evolutionary process.

Other fossil finds at the site, (wood, leaves, and other plant material), suggest that during this global warm phase these camels lived in a boreal-type forest dominated by Larch trees, and had plenty to eat. There was 24 hour sunshine in the summer, and months of darkness in the snowy winter. The camels grew heavy coats and survived on fats stored in their humps during the long winter months.

Camels originated in North America some 45 million years ago.  Todays camels are known from arid regions that extend from northern Africa to the Asian interior. Their nearest living relatives are llamas, alpacas, vicuñas and guanacos.

The Ellesmere Island camel fossil specimen is housed at the Canadian Museum of Nature’s research and collections facility in Gatineau, Quebec. The specimen forms part of the lateral surface of a large tibia, (the main lower leg-bone in mammals). The Ellesmere tibia is estimated to have been approximately 30% larger than that of modern camels. This ancient camel would have measured 9 feet, at the shoulder and weighed in at about 900 kilograms. (2,000 pounds). Other fossil remains found on Ellesmere Island were those of ancient black bears, a three-toed horse, beaver, deerlet and badger. 

The Canadian Museum of Nature is Canada’s national museum of natural history and natural sciences. It promotes awareness of Canada’s natural heritage through traveling exhibitions, public education programs and scientific research. They provide the maintenance for a 10.5 million-specimen collection. The museum’s legacy of Arctic research dates back 100 years to the first Canadian Arctic Expedition of 1913.

About the Author

Rosemary and her husband Bruce own and operate Spring Valley Farms Llamas and Alpacas on Denman Island, British Columbia. She is currently actively involved with the Vancouver Island Llama and Alpaca Club. Visit Rosemary at llamapackingtours@gmail.com