Understanding Unconventional CD8+ T cell Responses in Protection from HIV
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Principal Investigator: Scott G Hansen Organization: OREGON HEALTH & SCIENCE UNIVERSITY Fiscal Year: 2021 Award: $800,450 Funding agency: National Institute of Allergy and Infectious Diseases Project Summary With 36 million people currently living with HIV worldwide, developing a prophylactic HIV vaccine that protects against sexual transmission remains a top global health priority. A pre-clinical HIV vaccine approach based on strain 68-1 of rhesus cytomegalovirus expressing SIV antigens (RhCMV/SIV) elicits cellular unique unconventionally MHC-restricted T cell responses that are able to stringently control and ultimately clear pathogenic SIV replication in ~50% of vaccinated rhesus macaques (RM). However, it remains unknown if the 68-1 RhCMV-induced unique immunity and protection from SIV is a RM-specific phenomenon. To investigate this question as a means to successfully translation RhCMV into the clinic as an HIV vaccine, we will recapitulate these results using a Mauritian cynomolgus macaques (MCM), a nonhuman primate species with unique MHC genetics that reflect human immunogenetics. In specific aim 1, we will characterize the cellular immune response engendered in MCM vaccinated with CyCMV/SIV vaccine vectors. In specific aim 2, we will measure the ability of CyCMV/SIV to protect MCM from pathogenic SIV replication following low dose challenge. In specific aim 3, we will examine whole blood RNA transcriptomic profiles to identify correlates of immune protection. Successful completion of these studies will further our understanding of the unique protection afforded by CMV vectors and facilitate successful clinical translation of CMV as a prophylactic HIV vaccine. Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Alleles><Allelomorphs><Animals><Antigens><Bio-Informatics><Bioinformatics><Blood Plasma><Blood Plasma Cell><Blood Sample><Blood specimen><Body Tissues><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><CMV><Cell Mediated Immunology><Cell Protection><Cell-Mediated Immunity><Cellular Immunity><Clinic><Complex><Crab-Eating Macaque><Crab-Eating Monkey><Cynomolgus Monkey><Cynomolgus macaque><Cytomegalovirus><Cytoprotection><Development><Dose><Dose-Limiting><Effectiveness><Endothelial Cells><Event><Exhibits><Expression Signature><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profile><Gene Expression Profiling><Genes><Genetic><HCMV><HIV><HIV vaccine><HIV-1><HIV-I><HIV/AIDS Vaccines><HIV1><Health Priorities><History><Human><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><Immune><Immune response><Immunes><Immunity><Immunochemical Immunologic><Immunogenetics><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunomodulation><Individual><Infection><LAV-HTLV-III><LYT3><Lymphadenopathy-Associated Virus><M fascicularis><M mulatta><M. fascicularis><M. mulatta><Macaca><Macaca fascicularis><Macaca mulatta><Macaque><Maps><Measures><Mediating><Micro RNA><MicroRNAs><Modeling><Modern Man><Monitor><Non-Polyadenylated RNA><Pathogenicity><Phase><Plasma><Plasma Cells><Plasma Serum><Plasmacytes><Population><Position><Positioning Attribute><Property><RNA><RNA Gene Products><Recording of previous events><Research><Reticuloendothelial System, Serum, Plasma><Rhesus><Rhesus Macaque><Rhesus Monkey><Ribonucleic Acid><Role><SIV><SIV Vaccines><Salivary Gland Viruses><Sexual Transmission><Simian Immunodeficiency Viruses><Site><T cell response><T8 Cells><T8 Lymphocytes><Tissues><Transcript Expression Analyses><Transcript Expression Analysis><Translations><Vaccinated><Vaccines><Variant><Variation><Viral Burden><Viral Load><Viral Load result><Viremia><Virus-HIV><Whole Blood><base><cell type><clinical translation><cytomegalovirus group><developmental><gene expression analysis><gene expression assay><gene expression pattern><gene expression signature><global health><host response><human immunodeficiency virus vaccine><immune modulation><immune regulation><immune system response><immunogen><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><improved><mRNA seq><mRNA sequencing><mRNA-seq><mRNAseq><miRNA><miRNAs><new vaccines><next generation vaccines><non-human primate><nonhuman primate><novel vaccines><plasmid vaccine><plasmocyte><pre-clinical><preclinical><prevent><preventing><prophylactic><repair><repaired><response><sexually transmitted><simian immunodeficiency virus vaccines><social role><transcriptional profile><transcriptional profiling><transcriptional signature><transcriptomics><vector><vector vaccine><viraemia><viral sepsis><virusemia>