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

Coronaviruses (CoVs) are one of the major viral pathogens that primarily target the human respiratorysystem. Previous outbreaks include the severe acute respiratory syndrome (SARS)-CoV and theMiddle East respiratory syndrome (MERS)-CoV which were characterized as agents that are a greatpublic health threat. In December 2019, the novel SARS-CoV-2 that causes COVID-19 emerged tobecome a worldwide pandemic. By April 10th, 2020 COVID-19 caused serious illness in more than 1.7million individuals and more than 100,000 deaths (https://www.worldometers.info/coronavirus/).Furthermore, it is noteworthy that immunocompromised individuals, such as cancer patients, areparticularly 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 underscoresthe urgent need to develop a rapid-response capability to produce anti-viral therapies that couldmitigate the impact of this disease, as well as future diseases1. To address this need, the University ofNebraska Medical Center (UNMC) and SAb Biotherapeutics (SAb) propose to utilize transchromosomicbovine (Tc bovine) technology to rapidly produce human anti-SARS-CoV-2 polyclonal IgG antibodiesfor use as an immunotherapeutic for COVID-19 patients. The basis of this approach is the unique Tcbovine technology in which the genes encoding the IgG antibodies produced by these animals arereplaced with their human counterparts. Thus, the vaccination of these animals with antigen results inthe large-scale production of antigen-specific human polyclonal antibodies directed to that antigen. Torapidly 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 thenbe purified and used for therapeutic and/or prophylactic purposes in the fight against COVID-19. Ourapproach 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 beeffectively applied broadly to a large patient population. Importantly, this approach has already provensuccessful in preventing MERS-CoV5 and Ebola6 in animal studies. In fact, SAb has already put ahuman anti-MERS-CoV polyclonal antibody product through Phase 1 clinical trials7. It is noteworthythat during the Ebola outbreak researchers observed in survivors early and increasing levels of IgGdirected 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 surfaceglycoprotein. Once the human polyclonal Abs are generated, UNMC will conduct in vitro and in vivoefficacy studies and will seek FDA approval to clinically evaluate the immunotherapeutic in humans atthe UNMC biocontainment facility.