MULTIMERIC BIOTHERAPEUTICS, INC. — Department of Health and Human Services SBIR Phase I: 300

Description

DESCRIPTION provided by applicant Hepatitis B virus HBV infection while preventable by routine vaccination has already led to chronic HBV infection CHB in about million people worldwide Although antiviral drugs are available these must be taken daily for life and are unaffordable for most of worldandapos s CHB population Consequently a therapeutic vaccine is needed that would stimulate sufficient immunity to control CHB Because CD T cells are both necessary and sufficient for clearing HBV from the liver a therapeutic vaccine must elicit extremely strong anti HBV CD T cell responses Such a vaccine must be strong enough to counter the PD PD L and CD regulatory T cells Tregs that suppress effective anti HBV CD T cells in CHB Mouse studies have shown that stimulation the CD receptor on dendritic cells can generate anti HBV CD T cells that are strong enough to overcome these suppressive mechanisms and lead to long term HBV control Consequently this project aims to use a powerful form of soluble multi trimer CD ligand CD L in conjunction with the HBV Core antigen HBcAg The result is a fusion protein comprised of the multimerization scaffold SPD with Core antigen and CD L SPD Core CD L This is referred to as a Multi Trimer Antigen Adjuvant Vaccine or andquot MagaVax andquot The Aims are to make the construct in an adenoviral vector test its effectiveness at eliciting anti HBV CD T cells in mice in vivo and show that i can activate human dendritic cells to present Core antigen to HBV specific human CD T cells in vitro When these studies are complete a MagaVax HBV vaccine will be ready for further testing and development as treatment for CHB PUBLIC HEALTH RELEVANCE Chronic hepatitis B virus HBV infection is a condition that affects million people worldwide and that kills by causing cirrhosis and liver cancer This project will develop a therapeutic vaccine for chronic HBV infection that is designed to stimulate immunity strong enough to clear HBV from the body