Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model

• DOI: 10.1371/journal.ppat.1010469
• Publication Date: 2022-04-29T17:29:46Z
• Authors: Sen-Mao Tien; Po-Chun Chang; Yen-Chung Lai; Yung-Chun Chuang; Chin-Kai Tseng; Yu-San Kao; Hong-Jyun Huang; Yu-Peng Hsiao; Yi-Ling Liu; Hsing-Han Lin; Chien-Chou Chu; Miao-Huei Cheng; Tzong-Shiann Ho; Chih-Peng Chang; Shu-Fen Ko; Che-Piao Shen; Robert Anderson; Yee-Shin Lin; Shu-Wen Wan; Trai-Ming Yeh
• Keywords: Humanized mouse; Antibody-dependent enhancement

Dengue virus (DENV) which infects about 390 million people per year in tropical and subtropical areas manifests various disease symptoms, ranging from fever to life-threatening hemorrhage even shock. To date, there is still no effective treatment for DENV disease, but only supportive care. nonstructural protein 1 (NS1) has been shown play a key role pathogenesis. Recent studies have that anti-DENV NS1 antibody can provide protection by blocking the DENV-induced disruption of endothelial integrity. We previously demonstrated anti-NS1 monoclonal (mAb) protected mice all four serotypes challenge. Here, we generated humanized mAbs transferred them after infection. The results showed prolonged bleeding time skin were reduced, several days Mechanistic ability inhibit NS1-induced vascular hyperpermeability elicit Fcγ-dependent complement-mediated cytolysis as well antibody-dependent cellular cytotoxicity cells infected with DENV. These highlight mAb potential therapeutic agent