Document text
Principal Investigator: FRANCIS ALI-OSMAN
Organization: DUKE UNIVERSITY
Fiscal Year: 2020
Award: $160,934
Funding agency: National Cancer Institute
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.
Terms: <2019 novel coronavirus><2019-nCoV><Ab response><Address><Adjuvant><Advocate><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antibody Formation><Antibody Production><Antibody Response><Antibody-Dependent Enhancement><Antigen Targeting><Antigens><Antineoplastic Vaccine><Autoantigens><Autologous Antigens><Award><Back><Blood><Blood Reticuloendothelial System><Blood monocyte><Brain Neoplasia><Brain Neoplasms><Brain Tumors><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><COVID-19><COVID-19 vaccine><COVID19><COVID19 vaccine><Cancer Vaccines><Cell Body><Cell Mediated Immunology><Cell-Mediated Immunity><Cell-Mediated Lympholytic Cells><Cells><Cellular Immunity><Chemistry><Clinical Trials><CoV emergence><Cytolytic T-Cell><Cytotoxic T Cell><Cytotoxic T-Lymphocytes><Data><Dengue><Development><Disease><Disorder><Dorsum><Dose><Early-Stage Clinical Trials><Elderly><Electroporation><GVAX><GVAX Cancer Vaccine><Generations><Glial Cell Tumors><Glial Neoplasm><Glial Tumor><Glioma><Goals><Health><Health Care Providers><Health Personnel><Healthcare Providers><Healthcare worker><Human><Humoral Immunities><IV Infusion><Immune response><Immunity><Immunological response><Immunotherapeutic agent><In Situ><In Vitro><Infection><Inflammation><Intravenous infusion procedures><Kinetics><Leukapheresis><Leukocytapheresis><Marrow monocyte><Messenger RNA><Mice><Mice Mammals><Modeling><Modern Man><Murine><Mus><Neoplasm Vaccines><Neuroglial Neoplasm><Neuroglial Tumor><Patients><Performance><Phase><Phase 1 Clinical Trials><Phase I Clinical Trials><Play><Process><Production><Program Development><Proteins><RNA Viruses><Reagent><Recovery><Research Resources><Resources><Risk Factors><Role><SARS Virus><SARS corona virus><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Safety><Self-Antigens><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe acute respiratory syndrome coronavirus 2><Sterility><T cell response><T memory cell><T-Cell Epitopes><T-Cells><T-Lymphocyte><T-Lymphocyte Epitopes><T8 Cells><T8 Lymphocytes><Testing><Therapeutic Leukopheresis><Time><Toxic effect><Toxicities><Transfection><Tumor Immunity><Tumor Vaccines><Vaccinated><Vaccination><Vaccines><Viral><Viral Diseases><Virus Diseases><Wuhan coronavirus><advanced age><anti-tumor immunity><antibody biosynthesis><antibody-based immunity><antitumor immunity><cancer immunity><corona virus disease 2019><corona virus disease 2019 vaccine><coronavirus disease 2019><coronavirus disease 2019 vaccine><coronavirus emergence><develop a vaccine><development of a vaccine><developmental><efficacy testing><elders><electroporative delivery><emergent CoV><emergent coronavirus><emerging CoV><emerging coronavirus><gene electrotransfer><geriatric><glial-derived tumor><health care personnel><health care worker><health provider><health workforce><healthcare personnel><high risk group><high risk population><host response><immune drugs><immune-based therapeutics><immunogen><immunogenic><immunogenicity><immunoglobulin biosynthesis><immunologic preparation><immunologic therapeutics><immunoresponse><immunotherapeutics><immunotherapy agent><intravenous infusion><intravenous injection><killer T cell><late life><later life><mRNA><medical personnel><memory T lymphocyte><model of animal><model organism><monocyte><mortality><mutant><nCoV><neuroglia neoplasm><neuroglia tumor><neutralizing antibody><new CoV><new coronavirus><novel><novel CoV><novel coronavirus><older adult><older person><phase I protocol><pre-clinical study><preclinical study><response><senior citizen><severe acute respiratory syndrome-CoV><social role><sterile><thymus derived lymphocyte><treatment provider><tumor><tumors in the brain><vaccination strategy><vaccine development><vaccine for cancer><vaccine formulation><viral infection><virus infection><virus-induced disease>