CHARACTERIZATION OF DENGUE NEUTRALIZING ANTIBODIES USING RECOMBINANT ANTIBODIES TECHNOLOGY

IN THE LATE 1700S, EDWARD JENNER DESCRIBED INDUCED IMMUNITY IN WHICH HE DEMONSTRATED THAT INOCULATION WITH COWPOX PREVENTED ONE FROM DEVELOPING DISEASE AGAINST SMALLPOX. A CENTURY LATER, EMIL ADOLF VON BEHRING EXPLORED THE POTENTIAL OF PASSIVE IMMUNITY AS AN ANTI-TOXIN THERAPY AGAINST TETANUS. THESE PIONEER WORKS LAID THE CORNERSTONES FOR SUBSEQUENT VACCINE AND THERAPEUTIC ANTIBODY DEVELOPMENT AS WELL AS FOR TODAY?S EXPLODING IMMUNOTHERAPY RESEARCH. THE FIRST HALF OF THIS THESIS IS DEDICATED TO THE CLONING, EXPRESSION, AND CHARACTERIZATION OF MONOCLONAL ANTIBODIES OBTAINED FROM TWO NATURALLY INFECTED DENGUE PATIENTS. THIS LED TO THE SUBSEQUENT DISCOVERY AND FURTHER CHARACTERIZATION OF AN ANTIBODY THAT POSSESSES POTENT NEUTRALIZATION CAPACITY AGAINST ALL FOUR DENGUE VIRUS SEROTYPES. IN PARALLEL, AN ATTEMPT TO DESIGN ANTIBODIES THAT CAN CROSS-NEUTRALIZE ALL FOUR DENGUE VIRUS SEROTYPES BY AN ENGINEERING APPROACH WAS MADE AND WILL BE DESCRIBED IN THE SECOND HALF OF THIS THESIS. THIS THESIS

Author dc:creator

• XU MEIHUI

• Dengue, human, plasmablast, neutralizing antibody, antibody engineering, epitope mapping