Accelerating discovery of an efficacious Plasmodium vivax multivalent multi-stage vaccine
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Principal Investigator: John H Adams Organization: UNIVERSITY OF SOUTH FLORIDA Fiscal Year: 2022 Award: $975,965 Funding agency: National Institute of Allergy and Infectious Diseases Project Summary/Abstract Plasmodium vivax is the second leading cause of malaria and the most prevalent cause of malaria outside of Africa. The estimated cost of the global burden of vivax malaria is $1.4 - $4 billion per year and more people live at risk worldwide from P. vivax than P. falciparum. It is endemic mostly in poor countries where access to affordable health care is lacking, which leads to lost adult productivity. Relapse infections from P. vivax poses a special challenge to malaria elimination and eradication because of its ability to repeatedly restart blood-stage infections from hypnozoites – the dormant parasite that can persist in human livers from weeks to years after the sporozoite infection. Exacerbating the problem, P. vivax transmission occurs prior to onset of clinical signs and treatment options to clear relapsing parasites in the dormant liver stage are limited. The goal of this U01 project is to accelerate vivax malaria vaccine development by validation of an optimal combination of P. vivax target antigens in pre-erythrocytic stages. Our vaccine strategy seeks to validate candidate antigens that together can effectively inhibit sporozoite infection and block liver stage development, including blood stage breakthrough infection. Our strategy exploits our new in vitro functional assay for experimental studies of liver stage development of P. vivax. We will pursue a structural vaccinology approach, using broadly neutralizing binding inhibitory antisera and monoclonal antibodies to identify and characterize the highest value immunogens and vaccine delivery method to design a multivalent vaccine to prevent and eliminate vivax malaria. Terms: <21+ years old><Adjuvant><Adult><Adult Human><Africa><Aliquot><Animals><Antibodies><Antibody Response><Antibody titer measurement><Antigen Targeting><Antigen-Presenting Cells><Antigenic Determinants><Antigens><Antisera><Assay><Binding><Binding Determinants><Binding Proteins><Bioassay><Biologic Assays><Biological Assay><Blood><Blood Reticuloendothelial System><Blood erythrocyte><Burma><Cell Body><Cells><Clinical><Clinical Treatment Moab><Country><Cryofixation><Cryopreservation><Culicidae><Development><Ensure><Epitopes><Erythrocytes><Erythrocytic><Formulation><Future><Generalized Growth><Geographic Area><Geographic Locations><Geographic Region><Geographical Location><Goals><Growth><Healthcare><Hepatic Cells><Hepatic Parenchymal Cell><Hepatocyte><Human><Immune><Immune Sera><Immune response><Immunes><Immunity><Immunization><Immunize><Immunoassay><Immunochemical Immunologic><Immunologic><Immunologic Sensitization><Immunologic Stimulation><Immunological><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunologically><Immunologics><Immunostimulation><In Vitro><Individual><Infection><Infection prevention><Laboratories><Laboratory Animals><Ligand Binding Protein><Ligand Binding Protein Gene><Limited Stage><Liver><Liver Cells><Malaria><Malaria Vaccines><Malarial Vaccines><Maps><Marrow erythrocyte><Methods><Mice><Mice Mammals><Modeling><Modern Man><Molecular Interaction><Monoclonal Antibodies><Mosquitoes><Murine><Mus><Myanmar><Nature><P falciparum><P vivax><P. falciparum><P. vivax><P.falciparum><Paludism><Parasites><Parasitic infection><Persons><Peru><Plasmodium Infections><Plasmodium falciparum><Plasmodium vivax><Plasmodium vivax Malaria><Prevent infection><Process><Productivity><Property><Protein Binding><RNA vaccine><RNA-based vaccine><Recombinants><Red Blood Cells><Red Cell><Relapse><Risk><Seasons><Source><Sporozoites><Subunit Vaccines><Thailand><Tissue Growth><Transgenic Organisms><Transmission><Vaccination><Vaccine Antigen><Vaccine Design><Vaccines><Validation><Vivax Malaria><Work><accessory cell><adulthood><antibody titering><base><blood corpuscles><bound protein><breakthrough infection><cell type><cold preservation><cold storage><cost estimate><cost estimation><deliver vaccines><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><experiment><experimental research><experimental study><geographic site><global health><health care><hepatic body system><hepatic organ system><host response><immune serum><immune system response><immunogen><immunogenicity><immunoreactivity><immunoresponse><in vitro Assay><mAbs><mRNA vaccine><mRNA-based vaccine><migration><nano particle><nano-sized particle><nanoparticle><nanosized particle><ontogeny><parasite infection><prevent><preventing><protective efficacy><transgenic><transmission process><transmission-blocking vaccine><uptake><vaccine candidate><vaccine delivery><vaccine development><vaccine strategy><vaccines against malaria><vaccinology>