Immunologically impaired individuals respond poorly to vaccination, underscoring the need for alternative strategies to protect these vulnerable populations from COVID-19. The work contained in this thesis combines cell and monoclonal antibody engineering in an attempt to overcome the transient protective immunity afforded by passive monoclonal antibodies. Here, both mouse and human pluripotent stem cells engineered for safety and allogeneic acceptance were genetically modified to secrete potent SARS-CoV-2 neutralizing biologics (nBios). When transplanted subcutaneously, transgenic mouse embryonic stem cells and their differentiated derivatives deliver a supply of protective nBio titers for long periods of time in vivo, resulting in high and persistent plasma SARS-CoV-2 neutralizing activity. Altogether, this work establishes the foundation for a novel approach to passive immunization by demonstrating the potential for long-lived ‘off-the-shelf’ cell products that secrete neutralizing antibodies to confer sustained passive prophylaxis against current and future viral pathogens.