The vaccine for COVID-19 will take some time to be developed and mass-produced. As such, antibody therapies are the best choice for the time being. So, a biopharmaceutical company used cows to produce antibodies that can subdue the SARS-CoV-2 virus.
The novel polyclonal antibody therapy was developed and optimized by SAB Biotherapeutics, a biopharmaceutical company. Their therapy was based on cattle to produce polyclonal antibodies that could recognize multiple parts of a virus, compared to monoclonal antibodies. Moreover, the utilization of cows could ensure the mass production of polyclonal antibodies to meet the expected demand in the clinical setting. This therapy was found to be up to four times more effective than convalescent plasma therapy.
Main Differences between Monoclonal and Polyclonal Antibodies
Antibodies are special proteins found in the blood of humans and many animals. These proteins are triggered by a part of the immune system. Once that part activates, it signals specialized white blood cells called B cells to manufacture the proteins to stop a particular pathogen. However, the production of antibodies relies on the information obtained by other immune cells. Thus, it can take some time for an organism to generate a sufficient number of correct antibodies for an illness. This is why vaccines have been developed to spare people from symptoms and possible complications.
According to Pacific Immunology, a provider of custom antibodies, antibodies can be classified based on the variation of producing B cells. When B cells recognize an antigen, they can acquire information from a part of it. Human B cells only recognize one part of an antigen called an epitope. Antibodies produced by human B cells can only attach to one unique epitope, but in some animals, various B cells permit the recognition of multiple epitopes of an antigen. Hence, humans produce monoclonal antibodies while some animals may produce polyclonal antibodies.
In addressing diseases, polyclonal antibodies are generally better than monoclonal antibodies. They can be produced easily, inexpensively, and quickly. There is also no significant issue when it comes to storage. As such, research institutes tend to explore polyclonal antibodies in treating infections because of the high sensitivity rate to multiple epitopes. Polyclonal antibodies may even be more capable of affecting pathogens that mutated, which often include alterations in the epitopes.
However, the sensitivity rate and versatility of polyclonal antibodies can be problematic in clinical settings. These antibodies have a higher reactivity rate than monoclonal antibodies, meaning a person has a higher chance of developing an allergic reaction from polyclonal antibody therapy. The reason behind this is the recognition of multiple epitopes, which may include something that is not part of a pathogen. So, any polyclonal antibody therapy must be optimized to lower the odds of an allergic reaction.
Cow Antibodies May Become a Weapon against COVID-19
Even without any specific treatment for COVID-19, biomedical scientists managed to find therapies that may help patients. One of these nonspecific therapies is convalescent plasma therapy, wherein a survivor's antibodies are transfused into a patient. However, the therapy is often provided to critically-ill patients as a last resort. Although no one exactly knows how much help the therapy can give, some patients have recovered because of it.
At SAB Biotherapeutics, scientists successfully created antibodies that neutralized SARS-CoV-2. The antibodies were tested in vitro and found to be four times more effective than convalescent plasma therapy. The creation of the new antibodies involved zero human plasma donors. Unlike plasma therapy, the SAB-185 therapeutic candidate used polyclonal antibodies to detect multiple epitopes of the viral antigen.
On May 28, 2020, the company announced the in vitro results and where the antibodies came from. They revealed that the novel therapy was leveraged from genetically engineered cattle to produce human-compatible polyclonal antibodies. Its design was optimized to be scalable and reliable for mass production, in case the demand surged. Scientists highlighted that SAB-185 was derived from the original SARS-CoV-2 strain in Wuhan. They believed that the therapy might sustain its efficacy even if the virus mutates in the future.
"In just seven weeks, we've accelerated development of a specifically targeted natural human polyclonal therapeutic, without the need for human serum, and generated large volumes of highly-potent neutralizing antibodies to SARS-CoV-2, to produce clinical lots of our COVID-19 therapeutic candidate, SAB-185," said Dr. Eddie J. Sullivan, President, CEO, and co-founder of SAB Biotherapeutics.
On June 5, 2020, the research on SAB-185 showed progress in scalability and reliability. Scientists were successful in the genetic alterations of specific cows in a barn in South Dakota. These altered cows could produce human polyclonal antibodies for SARS-CoV2. The success in cows indicated two major advantages.
First, dairy cows have lots more blood than humans and smaller animals. This permits the synthesis of human proteins within them. Second, dairy cows have two times more antibodies per milliliter of blood than people. That quantity is critical in sustaining the supply of therapeutic antibodies.
Scientists revealed that engineered dairy cows would require a starter to release the needed polyclonal antibodies. The animals would be immunized with a DNA vaccine that contained the SARS-CoV-2 genome. The introduction of the DNA would prepare the immune system. Next, a second injection that contained a part of the pathogen's spike protein would be administered. The second injection was necessary to facilitate the viral passkey to cells. A fully engineered dairy cow could produce polyclonal antibodies for hundreds of patients in a single month.
According to the 142nd Situation Report of the World Health Organization (WHO) of the United Nations, countries are in dire need of effective therapies against COVID-19. This is because the total confirmed cases peaked at 7,145,539 worldwide, as of June 10, 2020. Exactly 408,025 have died due to the novel disease across the globe. These numbers are expected to climb in the coming months since a vaccine can take a few years to become viable.
Therapies like polyclonal antibodies can further assist medical frontliners all over the world. Around 24.7 million personal protective equipment (PPE), 26 million medical masks, and more than N95 respirators procured by the WHO are set to be distributed in the Americas. While the shipment can help many frontliners, there is still a huge shortage. If a functional therapy can substantially lower the number of COVID-19 patients, its impact will decrease the demand of PPE across various settings and save more medical frontliners who have been at risk of premature death since the start of this pandemic.