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

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

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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

Original languageEnglish
Article numbere1010469
JournalPLoS pathogens
Volume18
Issue number4
DOIs
Publication statusPublished - 2022 Apr

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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