MIT Technology Review - Cattle that can crank out human antibodies are being tested as a first line of defense against infectious diseases.
During the most recent Ebola outbreak in West Africa, health-care workers treated some sick patients by injecting them with plasma—the translucent part of the blood—taken from individuals who had survived the disease. In the absence of an approved drug to treat patients, the hope was that protective proteins in the donor plasma would help recipients fight the disease and recover.
A biotech company wants to use this same approach to treat a variety of infectious diseases, with one key difference: cows, not humans, will be the plasma donors.
SAB Biotherapeutics of South Dakota has genetically engineered cattle to produce large quantities of human antibodies—proteins that help remove harmful foreign pathogens from the body—in a rapid fashion that could be used to treat patients suffering from infectious diseases like Middle East respiratory syndrome (MERS), Ebola, and influenza. The World Health Organization recently recognized the company’s approachamong six promising new technology platforms that could help respond to disease outbreaks worldwide.
“The entire idea behind this is that human antibodies are the natural way that our bodies fight disease,” says Eddie Sullivan, president and CEO of SAB Biotherapeutics.
Sullivan and his colleagues engineered the cows by knocking out a section of genes in the animals and replacing it with a human artificial chromosome containing the genetic information to generate human antibodies. They then vaccinated the cows with a target disease antigen, a foreign substance that induces an immune response in the body and spurs the production of antibodies. Once the cows have produced enough antibodies, scientists can harvest the animals’ plasma and separate the antibodies from the plasma to create a therapeutic drug. The whole process, from vaccinating the cows to the end product, takes about two and a half months, making it rapidly scalable in the event of a disease outbreak.
Scientists have previously tried using antibodies derived from animals in an attempt to treat disease. But animal-based antibodies can produce severe side effects in people. Sullivan thinks this is less likely to happen with SAB’s antibodies since the cows are producing antibodies that appear to be fully human.
Antibodies in plasma, also known as immunoglobulin therapy, have been used for decades to treat a variety of diseases. But one major limitation is that so much of it is needed for the treatment to be effective. The benefit of using the genetically engineered cows is that they are able to produce human antibodies in much higher quantities than people can. Sullivan says one cow can produce anywhere from 300 to 1,000 human doses per month, depending on the disease.
During the Ebola outbreak, researchers showed that deaths in patients who received plasma from survivors were only slightly lower than a control group that didn’t receive a plasma transfusion—31 percent compared to 38 percent. But that doesn’t mean convalescent plasma doesn’t work; the authors note that health-care workers didn’t have time to measure the level of antibodies present in the donor plasma.
The National Institutes of Health is currently testing SAB Biotherapeutics’s cow-derived human antibodies in healthy adults for the first time in a phase I safety trial for MERS. If shown to be safe, the company plans to test the drugs in a Phase II trial in countries with local MERS cases. SAB has also partnered with the U.S. Army Medical Research Institute of Infectious Diseases to test its approach against a wide range of pathogens, including hantavirus, a rare but deadly viral infection spread by rodents.
While the technology is promising, the WHO notes that it could be potentially costly to manufacture these drugs—at $2,000 per gram. Each cow can produce 150 to 600 grams of antibodies per month, according to Sullivan, which adds up to a hefty price tag. That high cost means that many of the countries that might benefit most from these drugs might not be able to afford manufacturing them on their own, the WHO report says.