COVID-19 Antigen Team for Immunotherapy and Monitoring Patient Immune Response

University Of Nebraska Medical Center, Omaha NE

Investigators

Linked publications, trials & patents

Abstract

Coronaviruses (CoVs) are one of the major viral pathogens that primarily target the human respiratory system. Previous outbreaks include the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome (MERS)-CoV which were characterized as agents that are a great public health threat. In December 2019, the novel SARS-CoV-2 that causes COVID-19 emerged to become a worldwide pandemic. By April 10th, 2020 COVID-19 caused serious illness in more than 1.7 million individuals and more than 100,000 deaths (https://www.worldometers.info/coronavirus/). Furthermore, it is noteworthy that immunocompromised individuals, such as cancer patients, are particularly vulnerable to COVID-19. There is currently no specific drug or vaccine to treat the COVID- 19 infection, only supportive care is being given to the infected individuals around the world. The speed with which the current COVID-19 pandemic has expanded across the globe underscores the urgent need to develop a rapid-response capability to produce anti-viral therapies that could mitigate the impact of this disease, as well as future diseases1. To address this need, the University of Nebraska Medical Center (UNMC) and SAb Biotherapeutics (SAb) propose to utilize transchromosomic bovine (Tc bovine) technology to rapidly produce human anti-SARS-CoV-2 polyclonal IgG antibodies for use as an immunotherapeutic for COVID-19 patients. The basis of this approach is the unique Tc bovine technology in which the genes encoding the IgG antibodies produced by these animals are replaced with their human counterparts. Thus, the vaccination of these animals with antigen results in the large-scale production of antigen-specific human polyclonal antibodies directed to that antigen. To rapidly develop such polyclonal antibodies, our COVID-19 antigen team is producing purified SARSCoV- 2 antigens for vaccinations to generate highly specific human polyclonal antibodies that will then be purified and used for therapeutic and/or prophylactic purposes in the fight against COVID-19. Our approach is similar to the use of convalescent serum from patients who have recovered from COVID- 19 to treat active cases of the disease2-4 but our approach will be more powerful in that it can be effectively applied broadly to a large patient population. Importantly, this approach has already proven successful in preventing MERS-CoV5 and Ebola6 in animal studies. In fact, SAb has already put a human anti-MERS-CoV polyclonal antibody product through Phase 1 clinical trials7. It is noteworthy that during the Ebola outbreak researchers observed in survivors early and increasing levels of IgG directed against the nucleoprotein, and other viral proteins, not against the surface glycoprotein8,9. Therefore our approach includes several SARS-CoV-2 antigens as well as the spike surface glycoprotein. Once the human polyclonal Abs are generated, UNMC will conduct in vitro and in vivo efficacy studies and will seek FDA approval to clinically evaluate the immunotherapeutic in humans at the UNMC biocontainment facility.