Correlation analysis of PCV was used to identify the relationship between nucleotide composition and synonymous codon usage pattern [42] . All statistical processes were carried out by with statistical software SPSS17.0 for windows. Development of a Humanized Antibody with High Therapeutic Potential against Dengue Virus Type 2 BACKGROUND: Dengue virus (DENV) is a significant public health threat in tropical and subtropical regions of the world. A therapeutic antibody against the viral envelope (E) protein represents a promising immunotherapy for disease control. METHODOLOGY/PRINCIPAL FINDINGS: We generated seventeen novel mouse monoclonal antibodies (mAbs) with high reactivity against E protein of dengue virus type 2 (DENV-2). The mAbs were further dissected using recombinant E protein domain I-II (E-DI-II) and III (E-DIII) of DENV-2. Using plaque reduction neutralization test (PRNT) and mouse protection assay with lethal doses of DENV-2, we identified four serotype-specific mAbs that had high neutralizing activity against DENV-2 infection. Of the four, E-DIII targeting mAb DB32-6 was the strongest neutralizing mAb against diverse DENV-2 strains. Using phage display and virus-like particles (VLPs) we found that residue K310 in the E-DIII A-strand was key to mAb DB32-6 binding E-DIII. We successfully converted DB32-6 to a humanized version that retained potency for the neutralization of DENV-2 and did not enhance the viral infection. The DB32-6 showed therapeutic efficacy against mortality induced by different strains of DENV-2 in two mouse models even in post-exposure trials. CONCLUSIONS/SIGNIFICANCE: We used novel epitope mapping strategies, by combining phage display with VLPs, to identify the important A-strand epitopes with strong neutralizing activity. This study introduced potential therapeutic antibodies that might be capable of providing broad protection against diverse DENV-2 infections without enhancing activity in humans. Dengue is the most important arthropod-borne viral disease in humans and an increasing public health concern in tropical and subtropical regions of the world. Approximately 50-100 million cases of dengue fever (DF) and 500,000 cases of dengue hemorrhagic fever (DHF) occur every year, and 2.5 billion people are at risk of dengue infection globally [1, 2] . Dengue infection may lead to fever, headache and joint pain in milder cases but may also lead to the more severe life-threatening DHF/dengue shock syndrome (DSS) has plasma leakage, thrombocytopenia, and hemorrhagic manifestations, possibly leading to shock [3, 4] .