Document text
Principal Investigator: Jae U Jung
Organization: CLEVELAND CLINIC LERNER COM-CWRU
Fiscal Year: 2024
Award: $989,903
Funding agency: National Cancer Institute
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) is a prevalent virus that establishes a lifelong persistent
infection in humans and is associated with Kaposi's sarcoma (KS) and primary effusion lymphomas (PELs).
Despite the reduction in complications associated with HIV infection due to combination antiretroviral
therapy, KS still occurs in individuals with well-controlled HIV infection, in older men without HIV infection
(classic KS), in sub-Saharan Africa (endemic KS), and in transplant recipients (iatrogenic KS). Despite
being a pressing human health problem, very little research has been conducted to date on potential
vaccine development against KSHV infection and its associated diseases. This is primarily due to the lack
of significant interest as well as the absence of an effective animal model that supports in vivo studies on
KSHV infection. For this reason, recombinant Murine Herpesvirus 68 (MHV68) has been used as the
murine counterpart of KSHV in a small, manageable mouse model. The goal of this U01 application is
twofold: firstly, to test three different novel vaccine platforms against KSHV infection, and secondly, to
develop chimeric MHV68 carrying the replacement of KSHV glycoprotein (MHV68-K-G) as a surrogate
challenge virus for testing the efficacy of KSHV vaccines in an in vivo mouse model.
Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Adverse effects><Affect><Africa South of the Sahara><Animal Model><Animal Models and Related Studies><Antibody Response><Antigens><Area><Attention><BAC clone><BACs><Bacterial Artificial Chromosomes><Basic Research><Basic Science><Codon><Codon Nucleotides><Development><Disease><Disorder><Engineering><Epidemic Parotitis Virus><Exhibits><Generations><Genes><Genetic><Glycoproteins><Goals><HHV-8><HHV8><HIV><HIV Infections><HTLV-III Infections><HTLV-III-LAV Infections><Health><Healthcare><Herpes infection><Herpesviridae><Herpesviridae Infections><Herpesviridae disease><Herpesvirus Infections><Herpesvirus Vaccines><Herpesviruses><Human><Human Herpesvirus 8><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><Iatrogenic Kaposi's Sarcoma><Immune response><Immunity><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunological response><Immunosuppressed Host><In Vitro><Individual><Infection><Infrastructure><KSHV><Kaposi Sarcoma><Kaposi Sarcoma-Associated Herpes Virus><Kaposi Sarcoma-Associated Herpesvirus><Kaposi sarcoma associated virus><Kaposi sarcoma herpes virus><Kaposi's Sarcoma><Kaposi's sarcoma (KS)-associated herpesvirus><LAV-HTLV-III><Link><Lymphadenopathy-Associated Virus><Measles virus><Measures><Messenger RNA><Mice><Mice Mammals><Modeling><Modern Man><Mouse herpesvirus strain 68><Multiple Hemorrhagic Sarcoma><Mumps virus><Murid herpesvirus 4><Murine><Murine herpesvirus 68><Mus><Myxovirus parotitidis><Play><Population><Preventive><Process><Production><Protein Subunits><Proteins><RNA vaccine><RNA-based vaccine><Recombinants><Research><Research Resources><Resources><Role><Safety><Side><Sub-Saharan Africa><Subsaharan Africa><Subunit Vaccines><Technology><Testing><Transplant Recipients><UTRs><Untranslated Regions><Vaccinated><Vaccine Antigen><Vaccine Design><Vaccines><Variant><Variation><Viral><Viral Diseases><Viral Pathogenesis><Viral Vector><Virus><Virus Diseases><Virus Replication><Virus-HHV8><Virus-HIV><Vulnerable Populations><antiretroviral therapy><antiretroviral treatment><assess effectiveness><chronic infection><determine effectiveness><develop a vaccine><develop vaccines><development of a vaccine><developmental><effectiveness assessment><effectiveness evaluation><efficacy testing><evaluate effectiveness><examine effectiveness><experience><flexibility><flexible><health care><herpes virus><high risk><host response><immune system response><immunogen><immunogenicity><immunoresponse><immunosuppressed patient><in vivo><in vivo Model><interest><kaposi's sarcoma herpesvirus><kaposi's sarcoma-associated human herpesvirus><lipid based nanoparticle><lipid nanoparticle><mRNA><mRNA lipid nano particle vaccine><mRNA vaccine><mRNA-LNP based vaccine><mRNA-LNP combination vaccines><mRNA-LNP vaccines><mRNA-based vaccine><model of animal><mouse model><murine model><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><new vaccines><next generation vaccines><novel><novel vaccines><older men><persistent infection><plasmid vaccine><primary effusion lymphoma><recombinant virus><rougeole virus><rubeola virus><self assembly><social role><tool><transplant patient><vaccine candidate><vaccine development><vaccine efficacy><vaccine platform><vector vaccine><vector-based vaccine><viral infection><viral multiplication><viral replication><viral testing><virus infection><virus multiplication><virus pathogenesis><virus testing><virus-induced disease><vulnerable group><vulnerable individual><vulnerable people>