With unprecedented speed and scale, SARS-CoV-2 has caused a deadly global pandemic. A safe and effectivevaccine to control this new pathogen is desperately needed. To address this need, GeoVax is leveraging itsunique GV-MVA-VLPTM platform and advanced antigen design to develop multiple vaccine candidates againstCOVID-19. Unique among COVID-19 vaccines, the GeoVax candidates are specifically designed to providehighly protective immunity against SARS-CoV-2 while avoiding antibody-dependent enhancement (ADE) andimmunopathology that have the potential to render vaccines not only ineffective but actually dangerous. Inaddition to the identification of the final vaccine candidate, the work proposed here will generate scientific datathat are extremely valuable to the overall field of COVID-19 vaccine development, in that testing of our uniquevaccines will determine whether application of our approach is able to overcome the ADE and immunopathologyrisks that plagued SARS vaccines. Under Specific Aim 1, we will complete the construction of GEO-CM02through GEO-CM04 vaccine candidates. We will then test these candidates to demonstrate antigen expression,manufacturability, formation of VLPs, and genetic stability under conditions designed to simulate those inmanufacturing, which will demonstrate the suitability of each vaccine construct as a candidate for full-scaleproduction. Finally, we will produce adequate amount of each vaccine to enable the animal studies planned inSpecific Aim 2 and ship the vaccines to our collaborators at the University of Texas Medical Branch. UnderSpecific Aim 2, we will then perform an immunogenicity and efficacy study in mice transgenic for humanangiotensin converting enzyme 2 (hACE2). The hACE2 transgenic mouse model is a rigorous animal modeldeveloped for SARS that is well suited for testing of human coronaviruses. We will immunize animals, samplethe animals for analysis of immune responses, challenge the animals with SARS-CoV-2, and monitor the animalspost-challenge for development of clinical signs of disease. Under Specific Aim 3, we will analyze samples fromthe hACE2 mouse study to assess the immunogenicity, efficacy and safety (ADE and immunopathology) of ourvaccine candidates. Immunogenicity analyses will include binding antibody (BAb) by ELISA, neutralizingantibody (NAb) by serum neutralization assay, antibody-dependent cellular cytotoxicity (ADCC) by cell-basedassay, and T cell responses by intracellular cytokine screening (ICS). Efficacy analyses will include viral loadand histopathology relative to unvaccinated controls. We will also analyze serum and tissue samples forevidence of ADE and immunopathology to test the hypothesis that our vaccines will avoid these risks associatedwith SARS vaccines. All these parameters will help to down select the most immunogenic (inducing broad Aband T cell responses) and safe (lack of ADE and immunopathology upon challenge) vaccine candidate for furthertesting in non-human primates and Phase 1 human trials. PROJECT NARRATIVE
Over the course of only a few months, the COVID-19 disease has killed hundreds of thousands of people,
sickened millions, paralyzed entire countries, and created massive economic damage. To end the current
COVID-19 pandemic and prevent future outbreaks of this disease, we propose a single well-designed project
including all work necessary to advance a COVID-19 vaccine to the point of readiness for clinical development.
The project will advance a promising safe and effective product for the prevention of COVID-19 and will also
generate scientific data that are extremely valuable to the overall field of COVID-19 vaccine development, in
that testing of our unique vaccines will determine whether application of our approach is able to overcome the
antibody-dependent enhancement (ADE) of infection and immunopathology risks that plagued work toward
SARS vaccines. Animals ; Antibodies ; antibody-dependent cell cytotoxicity ; Ab-dependent cellular cytotoxicity ; antibody dependent cell mediated cytotoxicity ; antibody dependent cytotoxicity ; antibody-dependent cellular cytotoxicity ; antibody-mediated cytotoxicity ; Antigens ; immunogen ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Cells ; Cell Body ; Dangerousness ; Disease ; Disorder ; Disease Outbreaks ; Outbreaks ; Economics ; Elements ; Engineering ; Enzyme-Linked Immunosorbent Assay ; ELISA ; Future ; Goals ; Human ; Modern Man ; Immunity ; In Vitro ; Infection ; Transgenic Mice ; Mus ; Mice ; Mice Mammals ; Murine ; Pathology ; Production ; Recurrence ; Recurrent ; Risk ; Safety ; Ships ; Technology ; Testing ; Texas ; Universities ; Vaccines ; Work ; cytokine ; base ; Phase ; Medical ; Blood group antigen S ; S antigen ; Serum ; Blood Serum ; nonhuman primate ; non-human primate ; Antibody-Dependent Enhancement ; Immunological response ; host response ; immune system response ; immunoresponse ; Immune response ; Genetic ; Viral Burden ; Viral Load ; Viral Load result ; Country ; neutralizing antibody ; Palsy ; Plegia ; paralysis ; paralytic ; Paralysed ; immunopathology ; develop a vaccine ; development of a vaccine ; vaccine formulation ; vaccine development ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; Histopathology ; Speed ; novel ; Sampling ; response ; immunogenic ; Molecular Interaction ; Binding ; evaluate vaccines ; vaccine screening ; vaccine testing ; vaccine evaluation ; SARS ; SARS coronavirus disease ; SARS-CoV disease ; Severe Acute Respiratory Syndrome CoV disease ; Severe Acute Respiratory Syndrome coronavirus disease ; Severe Acute Respiratory Syndrome ; Tissue Sample ; preventing ; prevent ; Preparedness ; Readiness ; Address ; Data ; Vaccine Design ; Development ; developmental ; pandemic disease ; pandemic ; vaccine efficacy ; immunogenicity ; design ; designing ; efficacy evaluation ; efficacy analysis ; efficacy assessment ; efficacy examination ; evaluate efficacy ; examine efficacy ; mouse model ; murine model ; vaccine candidate ; protective efficacy ; T cell response ; screening ; clinical candidate ; efficacy study ; clinical development ; preclinical development ; pre-clinical development ; Immunize ; manufacturability ; COVID-19 ; COVID19 ; CV-19 ; CV19 ; corona virus disease 2019 ; coronavirus disease 2019 ; 2019-nCoV ; 2019 novel corona virus ; 2019 novel coronavirus ; COVID-19 virus ; COVID19 virus ; CoV-2 ; CoV2 ; SARS corona virus 2 ; SARS-CoV-2 ; SARS-CoV2 ; SARS-associated corona virus 2 ; SARS-associated coronavirus 2 ; SARS-coronavirus-2 ; SARS-related corona virus 2 ; SARS-related coronavirus 2 ; SARSCoV2 ; Severe Acute Respiratory Distress Syndrome CoV 2 ; Severe Acute Respiratory Distress Syndrome Corona Virus 2 ; Severe Acute Respiratory Distress Syndrome Coronavirus 2 ; Severe Acute Respiratory Syndrome CoV 2 ; Severe Acute Respiratory Syndrome-associated coronavirus 2 ; Severe Acute Respiratory Syndrome-related coronavirus 2 ; Severe acute respiratory syndrome associated corona virus 2 ; Severe acute respiratory syndrome corona virus 2 ; Severe acute respiratory syndrome coronavirus 2 ; Severe acute respiratory syndrome related corona virus 2 ; Wuhan coronavirus ; coronavirus disease 2019 virus ; hCoV19 ; nCoV2 ; human coronavirus ; HCoV ; human CoV ; human corona virus ; COVID-19 vaccine ; 2019-nCoV vaccine ; COVID19 vaccine ; SARS-CoV-2 vaccine ; SARS-CoV2 vaccine ; SARS-coronavirus-2 vaccine ; Severe Acute Respiratory Syndrome CoV 2 vaccine ; Severe acute respiratory syndrome coronavirus 2 vaccine ; corona virus disease 2019 vaccine ; coronavirus disease 2019 vaccine ; vaccine against 2019-nCov ; vaccine against SARS-CoV-2 ; vaccine against SARS-CoV2 ; vaccine against SARS-coronavirus-2 ; vaccine against Severe Acute Respiratory Syndrome CoV 2 ; vaccine against Severe acute respiratory syndrome coronavirus 2 ; vaccine for novel coronavirus ; COVID-19 pandemic ; COVID crisis ; COVID epidemic ; COVID pandemic ; COVID-19 crisis ; COVID-19 epidemic ; COVID-19 global health crisis ; COVID-19 global pandemic ; COVID-19 health crisis ; COVID-19 public health crisis ; COVID19 crisis ; COVID19 epidemic ; COVID19 global health crisis ; COVID19 global pandemic ; COVID19 health crisis ; COVID19 pandemic ; COVID19 public health crisis ; SARS-CoV-2 epidemic ; SARS-CoV-2 global health crisis ; SARS-CoV-2 global pandemic ; SARS-CoV-2 pandemic ; SARS-CoV2 epidemic ; SARS-CoV2 pandemic ; SARS-coronavirus-2 epidemic ; SARS-coronavirus-2 pandemic ; Severe Acute Respiratory Syndrome CoV 2 epidemic ; Severe Acute Respiratory Syndrome CoV 2 pandemic ; Severe acute respiratory syndrome coronavirus 2 epidemic ; Severe acute respiratory syndrome coronavirus 2 pandemic ; corona virus disease 2019 epidemic ; corona virus disease 2019 pandemic ; coronavirus disease 2019 crisis ; coronavirus disease 2019 epidemic ; coronavirus disease 2019 global health crisis ; coronavirus disease 2019 global pandemic ; coronavirus disease 2019 health crisis ; coronavirus disease 2019 pandemic ; coronavirus disease 2019 public health crisis ; coronavirus disease crisis ; coronavirus disease epidemic ; coronavirus disease pandemic ; severe acute respiratory syndrome coronavirus 2 global health crisis ; severe acute respiratory syndrome coronavirus 2 global pandemic ; COVID-19 prevention ; COVID19 prevention ; coronavirus disease 2019 prevention ; prevent COVID-19 ; prevent COVID19 ; prevent coronavirus disease 2019 ; SARS-CoV-2 immunity ; COVID-19 immunity ; COVID19 immunity ; Severe acute respiratory syndrome coronavirus 2 immunity ; coronavirus disease 2019 immunity ; immunity against COVID-19 ; immunity against COVID19 ; immunity against SARS-CoV-2 ; immunity against Severe acute respiratory syndrome coronavirus 2 ; immunity against coronavirus disease 2019 ; immunity to COVID-19 ; immunity to COVID19 ; immunity to SARS-CoV-2 ; immunity to Severe acute respiratory syndrome coronavirus 2 ; immunity to coronavirus disease 2019 ; COVID-19 monitoring ; COVID19 monitoring ; SARS-CoV-2 monitoring ; coronavirus disease 2019 monitoring ; severe acute respiratory syndrome coronavirus 2 monitoring ; ACE2 ; angiotensin converting enzyme 2 ; angiotensin converting enzyme II ; emerging pathogen ; new pathogen ; novel pathogen ;
