Paper Title
THERAPEUTIC HUMAN MONOCLONAL ANTIBODY AGAINST DENGUE VIRUS: DOUBLE ACTION; VIRAL & SEVERITY REDUCTION

Abstract
Dengue hemorrhagic fever (DHF) cause by the mosquito borne Dengue virus (DENV) has become the world public health problem due to global warming and globalization. Each year, 100 million Dengue cases required hospitalization. World Health Organization aim to reduce Dengue mortality to be at 50% in the year 2020. But until present, there is no specific drug for Dengue treatment. By using SPYMEG myeloma cell fused with pheriperal blood mononuclear cell (PBMC) obtained from Dengue patients, the hybridoma cell producing neutralizing human monoclonal antibodies (NhuMAbs) anti envelope protein against 4 serotypes of DENV has been established at CEAR. Two candidates NhuMAb (clones 19 and 54) were successfully pre-clinically tested in vitro by 95-100 % neutralized all 4 serotypes of 20 clinical isolates DENV and in vivo tested by significantly decreased mortality of prior DENV intra-cranially mice and eliminated DENV (from 1010 to be 0) in blood of DENV challenged Marmoset monkeys within 2 days. To make NhuMAb without causing ADE, FC-modified at LALA position of both NhuMAb clones was established. Industrial scale production of NhuMAbs using the Food and drug administration (FDA) accepted method of Stable expressed Chinese Hamster Ovary (CHO) cell produced at GMP facility was prepared at the licensing company. AG129 mice that 24 hr. prior subcutaneously injected with 105 FFU DENV followed by treated with Fc-modified NhuMAb clone 54 showed almost 100 % survival. Moreover,the newly developed MAbs clones 8 and M20 could reduce the severity of Dengue virus in the in vitro tested. Keyword - Neutralizing, human monoclonal antibodies, Dengue virus, 4 serotypes, envelope protein