The Development of Humanized Monoclonal Antibody Therapy Targeting Dengue Virus NS1
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 is a potentially deadly complication, 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 occur in the setting of dengue virus infection, the team provides an humanized antibody, 33D2 to protect human from dengue virus infection and to treat the life-threatening dengue DHF/DSS. The humanized 33D2 Ab could induce complement-dependent lysis of dengue-infected but not un-infected cells in vitro. Furthermore, through mice either active immunization with the modified NS1-WD peptide or passive transfer of 33D2 Ab, the resulted data shown efficiently protected mice against all serotypes of dengue virus infection. More importantly, dengue patients with more antibodies recognized the modified NS1-WD peptide had less severe disease and this, further shed light on the development of the modified NS1-WD peptide and the 33D2 Ab for dengue vaccine prevention and the treatment of DHF/DSS.
Targeting on non-cross-reactive but four serotype-conserved region of NS1 33D2 Ab do not cause ADE Protective mechanisms via CDC and block secreted NS1-elicited pathogenesis effects Humanized antibody to treat DHF and DSS--first in human.
PCT applications for vaccine and the antibody have submitted in 2017 and 2018 respectively.
Licensee interests in Dengue infection for the vaccine or therapeutic humanized antibody development.
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