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SAB Biotherapeutics Mines Cow’s Antibodies for Treating COVID-19
By Ruchi Jhonsa, Ph.D.
In times of need, scientists are not leaving any stone unturned to overcome the pandemic situation. Researchers have now turned to cattle farms to find a solution for combating the novel coronavirus.
SAB Biotherapeutics, a growing biotech, is using genetically modified cows to generate human antibodies that can target SARS-CoV-2. These cattle are special as they carry a piece of human chromosome harboring the entire cassette of human immunoglobulin heavy chain and light chain capable of producing functional human polyclonal antibodies. When injected with a piece of the virus, these animals manufacture large quantities of human antibodies that can potentially neutralize the pathogen.
SAB, a South Dakota based company, has successfully developed antibodies against the novel SARS virus using its proprietary DiversitAbTM platform. Its candidate antibody, SAB-185 shows four times higher neutralization potency against the virus in comparison to the most potent human convalescent plasma samples evaluated so far. The company is collaborating with CSL Behring to ramp up the production of its antibody candidate as it gears to begin human trials in early summer. If approved, SAB-185 can be both used for the treatment of infected patients or for providing immunity from the infection to the front-line responders, mission-critical staff, and high-risk populations.
“These data indicate this human polyclonal antibody therapeutic has potent neutralizing activity against live SARS-CoV-2. The neutralizing titers of SAB-185 are significantly higher than those of the most potent plasma of recovered COVID-19 patients we’ve been able to source,” said William B. Klimstra, Ph.D. Associate Professor of Microbiology and Molecular Genetics, Associate Professor of Immunology and Member of the Center for Vaccine Research at The University of Pittsburgh. “We are still in the early stages of evaluating SAB-185, but the preliminary results are promising. My laboratory is conducting a series of studies to bring SAB-185 into clinical trials as soon as possible.”
Artificial Passive Immunity
When challenged by a pathogen, the body reacts by producing molecular fighters known as antibodies. From the beginning of the 20th century, scientists have been using these externally produced antibodies to fight off disease. This mode of treatment is known as artificial passive immunity in which the antibodies are mined from the patients’ blood that has been previously exposed to the pathogen and transferred to patients fighting the disease. The treatment was found effective during the Spanish flu outbreak and was later used for the treatment of Ebola, H1N1, and chikungunya.
While this treatment doesn’t provide long-term protection, it certainly mitigates the immediate effects of the infection. The effectiveness of this approach has pushed many companies to use either cell lines or animal models to develop polyclonal antibodies for treating COVID-19. Takeda and Grifols are already working on an antibody cocktail made from the plasma of patients who have fought the infection. However, this approach can be difficult to scale, as it requires several hundred patients to get a small batch of the product. Moreover, the antibody cocktail is heterogeneous and will contain antibodies against all kinds of diseases diluting the antibody in need.
An Incubator for COVID-19 Antibodies: DiversitAb Platform
DiversitAb is SAB’s proprietary platform that can rapidly develop and manufacture fully human polyclonal antibodies. The genetically engineered cows harboring the human immunoglobulin genes are immunized with the target disease antigen, and their plasma is harvested and purified for use as a human treatment.
Cows make an excellent source of antibodies for several reasons. First of all, “they have a lot more blood than the smaller animals,” which makes it possible to generate higher volumes of neutralizing antibodies with one shot of antigen. Depending upon the size and age, a cow can produce 150 to 600 grams of purified hIgG per month. Secondly, they have a robust immune response in comparison to humans. “Their blood can also contain twice as many antibodies per milliliter as human blood, says Eddie Sullivan, President, and CEO, SAB Biotherapeutics.
Additionally, cattle produce a diverse population of polyclonal antibodies when administered with the antigen, which means they can recognize a variety of epitopes on the spike protein. This is important in case the spike protein mutates and renders most of the other monoclonal vaccines ineffective. “This diversity may make the cow’s proteins more powerful than monoclonal antibodies, and they may remain effective even if a virus mutates,” said Dr. Sullivan.
SAB’s Experience with Coronaviruses
SAB has rich experience in working with coronaviruses and other viruses. Since 2014, they have produced a dozen antibodies against Zika, Ebola, seasonal influenza, MERS and SARS. The company has tasted success with its MERS antibody, SAB-301, which completed Phase 1 clinical safety trial and is now progressing to Phase 2/3 in the middle east with support from NIH (NIAID) and BARDA. According to Dr. Sullivan, the research on MERS treatment “gave us the initial knowledge to focus on the right target.” SABs COVID-19 efforts have been rewarded generously with funding from the US Department of Defense and BARDA.
Editor: Rajaneesh K. Gopinath, Ph.D.
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