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Principal Investigator: Kartik Chandran
Organization: UNIVERSITY OF TEXAS AT AUSTIN
Fiscal Year: 2024
Award: $428,507
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary/Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) causes a life-threatening tick-borne disease in humans.
The disease presents as a severe form of hemorrhagic fever with a case fatality rate of 10–40%. CCHFV
outbreaks have spanned a wide geographic area ranging from Western and Central Asia, the Middle East,
Africa and Southern Europe. Increasing global temperatures, migratory birds, and the international livestock
trade have all potentially contributed toward the spread of Hyalomma ticks—the primary vector for CCHFV.
Expanding endemic zones, widespread morbidity and significant mortality make CCHFV an acute threat to
public health and thus is listed as a NIAID Category A priority pathogen. The viral genome encodes a
glycoprotein precursor that is processed into two structural glycoproteins—Gn and Gc—and two secreted
glycoproteins—a mucin-like domain and GP38. Protective antibodies have been isolated that target Gc or
GP38, suggesting that these two proteins should be given priority for vaccine development. Here we
propose to engineer Gc- and GP38-based immunogens that focus the immune response onto broadly
conserved epitopes that are capable of eliciting protective antibody responses. To accomplish our goal, we
will structurally characterize CCHFV glycoproteins and their interactions with human-derived antibodies,
rationally engineer vaccine antigens based in part on the structural information, and characterize the
immune responses elicited by these antigens in animal models. These results will be used to guide further
improvements of the immunogens, including display on self-assembling multi-valent nanoparticles, and the
most promising candidates will be evaluated in a lethal murine model of CCHFV challenge. Given our
expertise, unique reagents, and preliminary data, we are confident that we can deliver a state-of-the-art
subunit vaccine candidate with the potential to induce cross-reactive protective antibodies, thereby
satisfying an unmet need against this NIAID Category A tick-borne pathogen.
Terms: <Acute><Africa><Alpha-Beta-Omega Interferon Receptor-1><Animal Model><Animal Models and Related Studies><Antibodies><Antibody Response><Antibody Therapy><Antigenic Determinants><Antigens><Antiviral Protein Alpha Type><Binding Determinants><Case Fatality Rates><Categories><Category A pathogen><Category A priority pathogen><Cell Body><Cells><Central Asia><Chimera Protein><Chimeric Proteins><Classification><Clinical Treatment Moab><Coloring Agents><Complex><Congo Virus><Congo Virus Infection><Congo hemorrhagic fever virus><Congo-Crimean Hemorrhagic Fever><Coronaviridae><Coronavirus><Crimean Hemorrhagic Fever><Crimean Hemorrhagic Fever Virus><Crimean-Congo Hemorrhagic Fever Virus><Crimean-Congo hemorrhagic fever orthonairovirus><Data><Data Protection><Disease><Disease Outbreaks><Disorder><Dyes><Engineering><Epitope Mapping><Epitopes><Evaluation><Family><Farm Animal><Filoviridae><Filovirus><Funding><Fusion Protein><Genome><Geographic Area><Geographic Locations><Geographic Region><Geographical Location><Glycoproteins><Goals><HuIFN-Alpha-Rec><Human><IFNAR><IFNAR1><IFNAR1 gene><IFNBR><IFRC><Immune response><Immunochemical Immunologic><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunosuppressed Host><Incidence><Interferon Alpha-Beta Receptor Alpha Chain><International><Ixodida><Laboratories><Licensing><Life><Livestock><Membrane Fusion><Mice><Mice Mammals><Middle East><Modern Man><Molecular><Monoclonal Antibodies><Morbidity><Morbidity - disease rate><Mucins><Mucus Glycoprotein><Murine><Mus><NIAID><Nairovirus><National Institute of Allergy and Infectious Disease><Outbreaks><Pathogenesis><Patients><Process><Proteins><Public Health><RNA Viruses><Reagent><Respiratory syncytial virus><Sampling><Site><Southern Europe><Structure><Subunit Vaccines><Systematics><Technology><Therapeutic antibodies><Tick-Borne Diseases><Ticks><Vaccine Antigen><Vaccine Design><Vaccines><Viral><Viral Diseases><Viral Envelope Proteins><Viral Genome><Viral Hemorrhagic Fevers><Virus><Virus Diseases><Western Asia><Work><antibody based therapies><antibody treatment><antibody-based therapeutics><antibody-based treatment><clinical development><corona virus><cross reactivity><design><designing><develop a vaccine><develop vaccines><development of a vaccine><disease prevention><disorder prevention><experience><geographic site><global temperature><hemorrhagic fever><host response><ifnar1 gene product><immune system response><immunogen><immunogenicity><immunoresponse><immunosuppressed patient><improved><in vivo><insight><interest><lead candidate><mAbs><medical countermeasure><migratory bird><model of animal><monoclonal Abs><mortality><mouse model><murine model><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><new vaccines><next generation vaccines><novel><novel vaccines><prevent><preventing><self assembly><structural glycoprotein><structural-GP><synergism><tick-borne><tick-borne illness><tick-borne pathogen><tickborne><tickborne disease><tickborne illness><tickborne pathogen><tool><type I IFN receptor><type I interferon receptor><vaccine candidate><vaccine development><vector><viral infection><virus genome><virus infection><virus-induced disease>