Project 3 Supplement - A Novel Cellular Tumor Vaccine Strategy for Mutant IDH1 glioma

Historically, stimulation of humoral immunity in the form of antibodies has been the most effective means to provide protection against most viral infections. For this reason, almost all SARS-CoV-2 vaccine efforts are focused on stimulating humoral immunity. At the same time, there is evidence to suggest that, as with other RNA viruses such as RSV and Dengue, stimulating protective humoral immune responses against SARS-CoV2 may not be feasible. The alternative, stimulating T cell immune responses to SARS-CoV-2, has been advocated as being the preferred means of inducing long term protective immunity. However, it is currently not known if T cell immunity by itself can protect against SARS-CoV-2 infection or the development of severe COVID-19. In addition, even if stimulating cellular immunity is the goal, it is not clear how this could best be achieved. Stimulating T cell responses, especially cytotoxic T cell responses, with vaccinations has proven to be difficult. We have developed a novel cellular vaccine strategy that induces very strong T cell, especially cytotoxic T cell, responses. In this strategy, circulating monocytes are purified from the blood, loaded with a target antigen, then given back by intravenous infusion. In animal models, this results in the development of much stronger T cell responses than we have been able to obtain with other vaccine strategies but no antibody responses. In the case of COVID-19, this monocyte vaccine platform provides an excellent opportunity to determine if T cell responses are sufficient to protect against SARS-CoV-2 infection or the development of severe COVID-19. In this supplement, we propose to perform critical preclinical studies that will be required by the FDA before a clinical trial of a COVID-19 monocyte vaccine can be approved. These studies include examining vaccine-induced immune responses to SARS-CoV-2 and the toxicity of monocyte vaccination in mice and demonstrating that we can formulate a human COVID-19 monocyte vaccine at a scale sufficient for a clinical trial.