Mason's NCBID and University of Costa Rica Develop Equine Antibody-based Therapeutic to Neutralize Coronavirus
Testing confirms formulations inhibit infectivity in culture cells and allow advancing to clinical trials.
Scientists at George Mason University’s National Center for Biodefense and Infectious Diseases (NCBID) reached a testing milestone in a collaboration with the University of Costa Rica’s Clodomiro Picado Institute to validate a new coronavirus equine antibody formulation to prevent COVID-19 disease from progressing in patients infected with the virus.
Costarican researchers, Dr. Alberto Alape Girón and Dr. Jose Gutierrez led a team utilizing their equine snake anti-venom experience to pioneer a new virus antibody creation system within the horses.
“They believe this technique of inoculation can be applied to produce large quantities of antibodies against coronavirus, for now, and for other viruses in the future,” said Dr. Charles Bailey, NCBID Director.
University of Costa Rica scientists have been working on the product development for three months. Recently, the team of Mason scientists confirmed that the formulations “are capable of inhibiting the infectivity of the SARS-Cov2, which produces the coronavirus,” said Carlos Araya, the rector of the University of Costa Rica.
“Our testing confirmed that the (Costa Rican) scientists’ strategy allows for antibodies that neutralize the virus, which prevents the disease from progressing in patients, preventing them from worsening,” said Dr. Aarthi Narayanan, Associate Professor of Systems Biology, and leader of Mason’s validation team.
This treatment is not a substitute for a vaccine, which fully protects those who have not been infected. Rather, it is a drug that lowers the effectiveness of the virus in the body of those who have already been diagnosed with COVID-19.
Clodomiro Picado Institute scientists achieved the drug by injecting coronavirus proteins into a group of horses, which, produce antibodies against these proteins.
Scientists then extracted blood from the horses which contain antibodies against Sars-Cov2, creating the therapeutic drug that can fight the virus in infected people. In other words, horses become “large quantity” plasma donors in place of previously infected people that have recovered from the infection. (Note: the horses were not injured in the process).
Now that the drug passed numerous levels of testing in the United States, the clinical study will begin in Costa Rica to test its effectiveness. If it passes this human test, it would be ready for use at all medical centers in the country.
Román Macaya, president of the Costa Rican Social Security Fund (CCSS), explained that this is the first time in the history of the CCSS that a clinical study of a product produced in Costa Rica will be carried out.
Macaya and Bailey helped establish a formal collaboration between George Mason University and its Costa Rican partners with a Memorandum of Understanding in March of 2017 to share scientific information and resources, allowing a greater study of mosquito-borne illnesses, such as Zika and Dengue fever which have a significant impact on Costa Ricans. Their research collaboration continues to have a positive impact on the citizens of Costa Rica.
“This is going to help us lower the viral load so that coronavirus patients can leave (the hospital) faster,” said Macaya.
“Our Mason scientists at the NCBID pursue research of consequence, making discoveries that can save lives around the world,” said Mason College of Science Dean Fernando Miralles Wilhelm. “It’s incredibly gratifying when innovative collaborations like this make impactful discoveries.”
This novel, cross-disciplinary approach to creating large-scale immunity has a low ecological impact, as the technique used is not pathogenic nor is the blood extraction procedure harmful to the horses.
According to Alape-Girón, a microbiologist and clinical chemist, “The results clearly demonstrate that the horses produced a large number of antibodies that block the entry of the virus into human cells. This indicates that the drug can be very efficient and that the amount required to treat the patients would be relatively low.”
Additionally, “the technology is very inexpensive and can be used effectively in low-income countries who may get vaccines later than others,” Bailey added. This combination of ecological sustainability and low cost of production makes this research prime candidate to help people the world over.
“We believe this technique of inoculation can be applied to produce large quantities of antibodies against coronavirus, for now, and for other viruses in the future,” said Bailey.
How did they do it? The science behind the discovery:
In the past four months, Clodomiro Picado Institute at the University of Costa Rica (ICP-UCR) researchers used various SARS-CoV-2 proteins to immunize six donated horses. The proteins induce the immune system of these animals to produce specific antibodies. In total, there were four immunizations with different combinations of SARS-CoV-2 proteins that did not harm the health of the animals.
The scientists extracted the blood and separated the blood cells from their liquid part, called plasma, which contains the antibodies. Then, the antibodies were purified at the pharmaceutical plant of the UCR's Clodomiro Picado Institute. Finally, they were used to formulate and package the drug, which is an injectable liquid.
"The proteins selected for immunization is the S1 protein, which is the viral protein that binds to the cellular receptor. Also the E and M proteins, as a recombinant construct, and the nucleocapsid N protein”, commented Dr. Guillermo León, coordinator of the Industrial Division of the ICP-UCR, in previous statements.
But that is not the only positive news. The formulations also successfully passed the sterility tests carried out by the Pharmaceutical Analysis and Advisory Laboratory (Layafa-UCR), in which the sera was found to meet the criteria of control and sterility.
"The quality test carried out in the Layafa-UCR showed the absence of aerobic bacteria, fungi and yeasts. It can be concluded that the sample analyzed is harmless (safe) from the point of view of microbial contamination," said Dr. Jeimy Blanco Barrantes, Laboratory coordinator.
Now, the most important step is next: the clinical study to be carried out by the CCSS. This will conclusively define if the formulations will be effective in treating patients with COVID-19. This analysis will compare the efficacy and clinical safety of the two equine antibody preparations in patients with COVID-19.
"The study, specifically, will evaluate the capacity of the treatment to help patients eliminate the virus from the tissues. We will use a quantitative test to be carried out at the Costa Rican Institute of Research and Teaching in Nutrition and Health (Inciensa) of the Ministry of Health. Also, the response of proinflammatory cytokines in patients receiving the treatment will be evaluated through specialized tests that will be carried out at the Faculty of Microbiology of the UCR," said Dr. Alape-Girón.
Currently, a group of professionals from the CCSS and the UCR School of Medicine are preparing the protocol to be used for the clinical study. Such protocol will be presented for evaluation and eventual approval to the CCSS Central Scientific Ethics Committee. For its part, the ICP-UCR will focus on optimizing the production of the new drug.
