Venezuelan (VEEV), eastern (EEEV), and western (WEEV) equine encephalitis viruses are arthropod-borne alphaviruses listed as CDC category B agents. There are currently no licensed human vaccines for the encephalitic alphaviruses, although conventional live-attenuated and formalin-inactivated vaccines for VEEV, EEEV, and WEEV have been developed and are currently utilized under IND status these vaccines have high reactogenicity and are poorly immunogenic. Ichor Medical Systems has demonstrated that a trivalent DNA vaccine candidate consisting of three DNA plasmids separately encoding the E1 and E2 glycoproteins of VEEV, EEEV and WEEV induce virus-neutralizing antibody responses consistent with protective immunity. Here we propose to further the development of this promising vaccine candidate by conducting IND-enabling safety/toxicology studies; this work encompasses both standard vaccine acute/chronic evaluation as well as cardiac monitoring to expand the safety database related to the clinical application of electroporation. In addition, preclinical immunogenicity experiments in nonhuman primates will be performed to facilitate the regulatory path toward approval of this product.
Public Health Relevance: This SBIR proposes to conduct preclinical immunogenicity and safety/toxicology studies on a trivalent DNA vaccine against Venezuelan (VEEV), Eastern (EEEV), and Western (WEEV) equine encephalitis viruses. The work conducted in this project will enable clinical testing of a novel vaccine for an unmet medical need and further the development of electroporation as a broad vaccine delivery platform.
Public Health Relevance Statement: NARRATIVE This SBIR proposes to conduct preclinical immunogenicity and safety/toxicology studies on a trivalent DNA vaccine against Venezuelan (VEEV), Eastern (EEEV), and Western (WEEV) equine encephalitis viruses. The work conducted in this project will enable clinical testing of a novel vaccine for an unmet medical need and further the development of electroporation as a broad vaccine delivery platform.
NIH Spending Category: Biodefense; Biotechnology; Emerging Infectious Diseases; Immunization; Infectious Diseases; Prevention; Vaccine Related; Vector-Borne Diseases
Project Terms: ATGN; Acute; Adjuvant; Alpha Virus; Alphavirus; Animals; Antibody Formation; Antibody Production; Antibody Response; Antigens; Arboviruses, Group A; Armed Forces Personnel; Arthropoda; Arthropods; Attenuated; Biodistribution; CDC; Canine Species; Canis familiaris; Cardiac; Categories; Cells; Centers for Disease Control; Centers for Disease Control (U.S.); Centers for Disease Control and Prevention; Centers for Disease Control and Prevention (U.S.); Characteristics; Chronic; Clinical; Clinical Evaluation; Clinical Research; Clinical Study; Clinical Testing; Clinical Trials; Clinical Trials, Phase I; Clinical Trials, Unspecified; Combined Vaccines; Common Rat Strains; Communicable Diseases; Consensus; DNA; DNA Maintenance; DNA Stability; DNA Vaccines; DNA delivery; Data; Data Banks; Data Bases; Databank, Electronic; Databanks; Database, Electronic; Databases; Deoxyribonucleic Acid; Development; Devices; Disease; Disorder; Dogs; Dose; E2 glycoprotein, VEEV; Early-Stage Clinical Trials; Electroporation; Encephalitis Viruses; Encephalitis, Equine; Encephalomyelitis, Equine; Equine Encephalomyelitis; Equine Encephalomyelitis Viral Infections; Equine Encephalomyelitis Virus Infections; Evaluation; Exhibits; Feedback; Formalin; Foundations; Goals; HIV vaccine; HIV/AIDS Vaccines; Human; Human, General; Immune response; Immunity; Immunization; Immunization Schedule; Immunologic Stimulation; Immunological Stimulation; Immunostimulation; Inactivated Vaccines; Inactivated Virus Vaccine; Individual; Infection; Infectious Disease Pathway; Infectious Diseases; Infectious Diseases and Manifestations; Infectious Disorder; Injection of therapeutic agent; Injections; Intramuscular; Investigation; Licensing; Life; Macaca; Macaque; Mammals, Dogs; Mammals, Mice; Mammals, Rabbits; Mammals, Rats; Man (Taxonomy); Man, Modern; Mediating; Medical; Medical Research; Method LOINC Axis 6; Methodology; Methods; Methods and Techniques; Methods, Other; Mice; Military; Military Personnel; Modeling; Monitor; Murine; Mus; Naked DNA Vaccines; Oryctolagus cuniculus; Performance; Phase; Phase 1 Clinical Trials; Phase I Clinical Trials; Phase I Study; Position; Positioning Attribute; Process; Product Approvals; Production; Programs (PT); Programs [Publication Type]; Protocols, Treatment; Public Health; RGM; Rabbit, Domestic; Rabbits; Rat; Rattus; Regimen; Research Design; Research Institute; Research, Medical; SBIR; SBIRS (R43/44); Safety; Sensitization, Immunologic; Sensitization, Immunological; Series; Small Business Innovation Research; Small Business Innovation Research Grant; South America; Staging; Study Type; Subunit Vaccines; System; System, LOINC Axis 4; Techniques; Technology; Testing; Toxicology; Translations; Treatment Protocols; Treatment Regimen; Treatment Schedule; United States; United States Centers for Disease Control; United States Centers for Disease Control and Prevention; Vaccines; Vaccines, Combination; Vaccines, Combined; Vaccines, DNA; Vaccines, Inactivated; Vaccines, Killed; Vaccines, Recombinant DNA; Vaccines, Subunit; Viral; Viral Diseases; Virus; Virus Diseases; Viruses, General; Work; aerosolized; antibody biosynthesis; base; biodefense; canine; clinical applicability; clinical application; clinical data repository; clinical data warehouse; clinical investigation; clinical test; cost effective; data repository; disease/disorder; domestic dog; experience; experiment; experimental research; experimental study; glycoprotein E2 VEE; healthy volunteer; host response; human immunodeficiency virus vaccine; immunogen; immunogenic; immunogenicity; immunoglobulin biosynthesis; immunoresponse; neutralizing antibody; new vaccines; next generation vaccines; non-human primate; nonhuman primate; novel; novel vaccines; pathogen; phase 1 study; phase 1 trial; phase I trial; plasmid DNA; pre-clinical; preclinical; preclinical study; programs; prophylactic; protective efficacy; protocol, phase I; public health medicine (field); public health relevance; relational database; research clinical testing; research study; response; safety study; study design; vaccine candidate; vaccine delivery; vaccine development; vector; viral infection; virus infection
