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Principal Investigator: RAVI THADHANI Organization: EMORY UNIVERSITY Fiscal Year: 2023 Award: $169,851 Funding agency: NIH Office of the Director Abstract The overall goal of this supplement is to develop vaccine strategies that induce strong neutralizing antibody response against HIV using mRNA and modified vaccinia Ankara (MVA) vaccine delivery platforms. To address the specific goals of the supplement, we will utilize samples obtained from studies conducted in the Emory Center for HIV/AIDS Vaccine and Cure Research consortium at the Emory National Primate Research Center. We propose to use the BG505 MD39 SOSIP mRNA as our vaccine strategy to elicit bnAbs. We hypothesize that BG505 MD39 mRNA delivered intramuscularly as either full length gp160 or truncated gp140 will induce HIV specific neutralizing antibodies with broad neutralization activity in rhesus macaques. Additionally, we would like to explore the effect of heterologous SIV Gag/Pol mRNA prime and MVA boost on the CD8 T cell response and evaluate how the route of immunization alters the ability of CD8 T cells to be boosted by MVA. We propose two specific aims. In Aim 1, we will compare the immunogenicity of MD39 gp160 and gp140 mRNA IM immunization. In Aim 2, we will characterize the immune response induced through heterologous mRNA prime and MVA boost and determine if the route of immunization effects the CD8 T cell response elicited by MVA. By completion of these aims we hope to develop improved vaccination strategy against HIV that can generate both neutralizing antibodies and T cells. Terms: <AIDS Virus><AIDS prevention><AIDS/HIV><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Affinity><Anatomic Sites><Anatomic structures><Anatomy><Antibodies><Antibody Response><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Biopsy><Bone Marrow><Bone Marrow Reticuloendothelial System><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><COVID><Cell Body><Cells><Clinical Trials><CoV disease><Conduct Clinical Trials><Epidemic><Follow-Up Studies><Followup Studies><Genetic Alteration><Genetic Change><Genetic defect><Germinal Center><Goals><Grant><HIV><HIV Prevention><HIV vaccine><HIV-1><HIV-I><HIV/AIDS><HIV/AIDS Vaccines><HIV/AIDS prevention><HIV1><Human><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><Immune response><Immunization><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Immunological response><Infection prevention><Inflammatory><Intramuscular><KI mice><Knock-in Mouse><LAV-HTLV-III><Length><Lymphadenopathy-Associated Virus><M mulatta><M. mulatta><Macaca mulatta><Measures><Messenger RNA><Modern Man><Modified Vaccinia Ankara><Modified Vaccinia Virus Ankara><Molecular Interaction><Mucosa><Mucosal Tissue><Mucous Membrane><Mutate><Mutation><NIH><National Institutes of Health><Outcome><Position><Positioning Attribute><Prevent infection><Prevention><Primates><Primates Mammals><Production><Proteins><RNA immunization><RNA vaccination><Research><Rhesus Macaque><Rhesus Monkey><Route><SIV><Sampling><Scientist><Simian Immunodeficiency Viruses><Structure of germinal center of lymph node><T cell response><T-Cells><T-Lymphocyte><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><United States National Institutes of Health><Vaccination><Vaccines><Viral><Virus-HIV><Visualization><corona virus disease><coronavirus disease><deliver vaccines><design><designing><develop a vaccine><develop vaccines><development of a vaccine><experiment><experimental research><experimental study><experiments><genome mutation><gp160><host response><human immunodeficiency virus vaccine><immune system response><immunization strategy><immunogen><immunogenicity><immunoresponse><improved><knockin mice><mRNA><mRNA immunization><mRNA vaccination><mouse model><murine model><neutralizing antibody><new vaccines><next generation vaccines><non-human primate><nonhuman primate><novel vaccines><resident memory T cell><response><subcutaneous><subdermal><thymus derived lymphocyte><tissue resident memory T cell><vaccination strategy><vaccine delivery><vaccine development><vaccine formulation><vaccine strategy>