Novel Hepatitis B Vaccine and Immunotherapy

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Principal Investigator: Mansun  Law
Organization: SCRIPPS RESEARCH INSTITUTE, THE
Fiscal Year: 2024
Award: $883,119
Funding agency: National Institute of Allergy and Infectious Diseases

Project Summary
Hepatitis B virus (HBV) infects over 250 million people worldwide and is a leading cause of liver
cirrhosis and cancer in many countries. The unique life cycle of HBV involves the generation of
covalently closed circular double stranded DNA (cccDNA) in the nucleus of an infected cell for
viral gene transcription and persistence. Current treatments only suppress viral replication. To
cure HBV, it will likely require a combination of drugs targeting the virus as well as boosting
antiviral immunity. In this project, we will apply the mRNA vaccine technology as a potent
vaccine and immunotherapy against HBV. A major scientific challenge is that the HBV vaccine
antigen, S, can disrupt protein homeostasis (proteostasis) leading to protein accumulation and
undesirable ER stress in the mammalian cells overexpressing the protein. We will investigate
the viral and cellular factors that hinder effective antigen expression, and improve the vaccine
antigens for elicitation of potent antibody and T cell responses to cure HBV infection. Success in
this project will also create new opportunities in the development of a multivalent mRNA vaccine
against common human pathogens.

Terms: <Accounting><Animals><Anti-viral Agents><Antibodies><Antibody Response><Antigens><Blood><Blood 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-19><CV-19><Cell Body><Cell Communication and Signaling><Cell Nucleus><Cell Signaling><Cell Surface Antigens><Cells><Cessation of life><Chronic Hepatitis B><Circulation><Cirrhosis><Clinical Data><Communicable Diseases><Coronavirus Infectious Disease 2019><Country><DNA><Death><Deoxyribonucleic Acid><Development><Double-Stranded DNA><Drug Combinations><Drug Targeting><Drug Therapy><ER stress><Engineering><Formulation><Gene Transcription><Generations><Genes><Genetic Alteration><Genetic Change><Genetic Transcription><Genetic defect><Glass><HBV><HBV Vaccine><HBV therapy><HBV treatment><Hepatic Cancer><Hepatic Cells><Hepatic Cirrhosis><Hepatic Disorder><Hepatic Parenchymal Cell><Hepatitis B><Hepatitis B Therapeutic><Hepatitis B Therapy><Hepatitis B Treatment><Hepatitis B Vaccines><Hepatitis B Virus><Hepatitis B virus vaccine><Hepatocarcinoma><Hepatocellular Carcinoma><Hepatocellular cancer><Hepatocyte><Hepatoma><Homologous Serum Hepatitis Virus><Immune><Immune Tolerance><Immune mediated therapy><Immune response><Immunes><Immunization><Immunologic Surface Markers><Immunologic Tolerance><Immunological Surface Markers><Immunological response><Immunologically Directed Therapy><Immunotherapy><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Intracellular Communication and Signaling><Investigation><Licensing><Life Cycle><Life Cycle Stages><Liver Cells><Liver Cells Carcinoma><Liver Cirrhosis><Liver diseases><Malignant neoplasm of liver><Mammalian Cell><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Messenger RNA><Modeling><Mutation><Nucleus><ORFs><Open Reading Frames><Patients><Persons><Pharmacotherapy><Prevention><Primary carcinoma of the liver cells><Process><Production><Prophylactic treatment><Prophylaxis><Protein Coding Region><Proteins><Public Health><RNA Expression><RNA vaccine><RNA-based vaccine><Recombinants><Regimen><Signal Transduction><Signal Transduction Systems><Signaling><Surface Antigens><Surface Proteins><System><T cell response><T-Cells><T-Lymphocyte><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><Technology><Transcription><Transfection><Vaccination><Vaccine Antigen><Vaccines><Viral><Viral Antigens><Viral Diseases><Viral Genes><Viral Hepatitis B><Viral Vaccines><Virus><Virus Diseases><Virus Replication><Yeasts><analog><anti-viral compound><anti-viral drugs><anti-viral immunity><anti-viral medication><anti-viral therapeutic><anti-virals><antigen processing><antiviral immunity><biological adaptation to stress><biological signal transduction><chronic HBV infection><chronic hepatitis B virus infection><chronic infection><cirrhotic><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><cost><develop a vaccine><develop vaccines><development of a vaccine><developmental><drug treatment><ds-DNA><dsDNA><efficacy testing><endoplasmic reticulum stress><fighting><genome mutation><hepatic disease><hepatopathy><host response><human disease><human pathogen><immune system response><immune system tolerance><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune unresponsiveness><immune-based therapies><immune-based treatments><immuno therapy><immunogen><immunogenic><immunological paralysis><immunoresponse><immunotherapeutic mRNA><improved><life course><liver cancer><liver carcinoma><liver disorder><liver malignancy><mRNA><mRNA immunotherapy><mRNA vaccine><mRNA-based approach for immunotherapy><mRNA-based immunotherapeutic><mRNA-based immunotherapy><mRNA-based vaccine><mRNA-mediated immunotherapeutic><malignant liver tumor><manufacturing process><messenger RNA immunotherapy><messenger RNA-based immunotherapy><mouse model><murine model><neutralizing antibody><non-human primate><nonhuman primate><novel><outcome following vaccination><outcome following vaccine><overexpress><overexpression><persistent infection><protein homeostasis><proteostasis><reaction; crisis><response><result following vaccination><result following vaccine><screening><screenings><serum hepatitis><stress response><stress; reaction><success><therapeutic vaccine><thymus derived lymphocyte><tool><treatment vaccines><vaccination outcome><vaccination result><vaccine against hepatitis B><vaccine candidate><vaccine development><vaccine efficacy><vaccine for the treatment><vaccine for treatment><vaccine outcome><vaccine result><viral DNA><viral infection><viral multiplication><viral replication><virus DNA><virus antigen><virus infection><virus multiplication><virus-induced disease>