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D18A0009

Humanized Antibody for the Treatment of Life-threatening Dengue Hemorrhagic Fever or Dengue Shock Syndrome

Project Description
Dengue virus infection is the most widespread arthropod-borne viral disease responsible for 390 million infections annually, mainly in tropical and sub-tropical countries.  An estimated 500 000 people with severe dengue require hospitalization each year and about 2.5% of those affected die as reported by WHO in 2015 to 2016.  Severe dengue has potentially deadly complications, e.g. life-threatening dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), which can result in plasma leaking, fluid accumulation, respiratory distress, severe bleeding, or organ impairment.  To combat the complicated immunopathogenic mechanisms underlying dengue disease, and to solve the risk of antibody (Ab)-dependent enhancement (ADE) symptom that occurs in the setting of dengue virus infection, our team provides a safe vaccine (modified NS1-WD peptide) and an antiviral antibody, 33D2 to protect human from dengue virus infection and to treat the DHF/DSS.  Both 33D2 Ab and modified NS1-WD peptide immune sera could induce complement-dependent lysis of dengue-infected but not un-infected cells in vitro.  Furthermore, through active immunization with the modified NS1-WD peptide or passive transfer of 33D2 Ab, the resulted data shown mice were efficiently protected against all serotypes of dengue virus infection.  More importantly, dengue patients with more antibodies recognized the modified NS1-WD peptide had less severe disease,, therefore the modified NS1-WD peptide and the 33D2 Ab are potential candidates for dengue vaccine development and the treatment of DHF/DSS.

Intellectual Property
PCT applications for vaccine and the antibody were filed in 2017 and 2018 respectively

Key Publications
Lai, Y. C., et al., Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus Infection, Scientific Reports, volume7, article number: 6975 (2017)

 
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