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Principal Investigator: Jesse Hong-Sae Erasmus
Organization: UNIVERSITY OF WASHINGTON
Fiscal Year: 2020
Award: $44,294
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
Viral replicons, or self-replicating RNA elements incapable of initiating a spreading infection, are
traditionally packaged into virus particles, termed viral replicon particles (VRPs), for in vivo
delivery. Alternatively, they can be encoded on a plasmid DNA and transfected for host cell
nucleus-mediated launch of replicating RNA. However, concerns of anti-vector immunity with
respect to the former, or genome integration in the latter approach has limited the clinical use of
such technologies. Furthermore, the development of VRPs has been restricted to larger viruses
that are capable of harboring additional genetic cargo. With improvements in the delivery of
naked RNA, there are now opportunities to develop new viral replicons without the constraints
provided by traditional delivery paradigms. By utilizing replicons derived from diverse positive-
strand RNA virus families, we can exploit the various mechanisms used by the host to detect
replicating viral RNA as well as the differential mechanisms of immune evasion utilized by the
parental virus, to rationally design vaccines. We propose studies that will elucidate the minimal
genetic elements derived from a small positive-stranded RNA animal virus that are required to
replicate and express a heterologous gene from a subgenomic transcript. We will then
demonstrate the translational applications towards vaccine development for Zika and
tuberculosis, viral and bacterial diseases with significant public health consequences.
Furthermore, we will perform comparative studies between this platform with existing platform
technologies derived from other positive-strand RNA virus families with the hypothesis that each
will elicit distinct innate and adaptive immune responses due to evolutionary differences of the
parental viruses.
Terms: <Alpha Virus><Alphavirus><Animals><Antigens><Astroviridae><Astrovirus><Bacterial Antigens><Bacterial Infections><Biological><Biology><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><Cancers><Capsid><Cell Body><Cell Nucleus><Cells><Clinical><Codon><Codon Nucleotides><Comparative Study><Complementarity Determining Regions><Complex><Complimentarity Determining Region><Development><Elements><Emerging Communicable Diseases><Emerging Infectious Diseases><Engineering><Enzyme Gene><Enzymes><Expression Profiling><Family><Family Picornaviridae><Flavivirus><Fluorescence Activated Cell Sorting Fractionation><Fluorescence-Activated Cell Sorting><Fluorescence-Activated Cell Sortings><Foundations><Frequencies><Gene Expression><Gene Transcription><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic Transcription><Genetic defect><Genome><Goals><Group A Arboviruses><Group B Arbovirus><Hypervariable Loop><Hypervariable Regions><IFN><Immune><Immune Evasion><Immune response><Immunes><Immunity><Immunoglobulin Hypervariable Region><Immunological response><Infection><Innate Immunity><Interferons><Libraries><Literature><M tuberculosis infection><M. tb infection><M. tuberculosis infection><M.tb infection><M.tuberculosis infection><MTB infection><Malignant Neoplasms><Malignant Tumor><Mediating><Methodology><Modification><Mutation><Mycobacterium tuberculosis (MTB) infection><Mycobacterium tuberculosis infection><Native Immunity><Natural Immunity><Non-Polyadenylated RNA><Non-Specific Immunity><Nonspecific Immunity><Nucleic Acid Vaccines><Nucleus><Pathway interactions><Phenotype><Picornaviridae><Picornaviruses><Procedures><Public Health><RNA><RNA Expression><RNA Gene Products><RNA Viruses><RNA delivery><RNA vaccine><Recombinant DNA><Recombinant DNA Molecular Biology><Replication Unit><Replicon><Ribonucleic Acid><Shapes><Structural Genes><Structure><Synthetic Immunogens><Synthetic Vaccines><System><T8 Cells><T8 Lymphocytes><TB infection><Technology><Testing><Therapeutic><Transcript><Transcription><Translations><Tuberculosis><Vaccine Design><Vaccines><Viral><Viral Antigens><Viral Diseases><Viral Genome><Virion><Virus><Virus Diseases><Virus Particle><Work><ZIKA><adaptive immune response><bacteria infection><bacterial disease><base><comparative><deep sequencing><design><designing><develop a vaccine><development of a vaccine><developmental><disseminated TB><disseminated tuberculosis><genetic element><genome mutation><genomic RNA><host response><immunogen><immunogenic><immunoresponse><in vivo><infection due to Mycobacterium tuberculosis><interest><mRNA vaccine><malignancy><mouse model><murine model><mutant><mutation scanning><mutation screening><neoplasm/cancer><new vaccines><next generation vaccines><novel><novel vaccines><nucleic acid delivery><particle><pathogen><pathway><plasmid DNA><rDNA><response><structural gene><tool><tuberculosis infection><tuberculous spondyloarthropathy><vaccine development><vaccine formulation><vector><viral RNA><viral infection><virus RNA><virus antigen><virus genome><virus infection><virus-induced disease>