1. A human bispecific neutralization antibody against four serotypes of dengue virus
- Author
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Jiansheng Lu, Wang Rong, Yunzhou Yu, Zhixin Yang, and Lei Chen
- Subjects
Serotype ,medicine.drug_class ,viruses ,Biology ,Dengue virus ,Antibodies, Viral ,Serogroup ,medicine.disease_cause ,Monoclonal antibody ,Neutralization ,Dengue ,Mice ,03 medical and health sciences ,Phagocytosis ,Neutralization Tests ,In vivo ,Virology ,Antibodies, Bispecific ,medicine ,Animals ,Humans ,Antibody-dependent enhancement ,030304 developmental biology ,0303 health sciences ,030302 biochemistry & molecular biology ,Antibodies, Monoclonal ,virus diseases ,Dengue Virus ,biochemical phenomena, metabolism, and nutrition ,Antibodies, Neutralizing ,Antibody-Dependent Enhancement ,Fragment crystallizable region ,Mice, Inbred C57BL ,biology.protein ,Antibody ,K562 Cells - Abstract
In tropical and subtropical countries, dengue virus (DENV) infections have been increasing; however, we still lack effective therapy. In the present study, we aimed to engineer a bispecific antibody (subsequently named LUZ-8F2-6B1), based on monoclonal antibody 6B1, which has anti DENV-1, 2, and 3 activity, and 8F2, which has anti DENV-4 activity. LUZ-8F2-6B1 displayed potent neutralization activity against four serotypes of DENV by binding to the envelop protein. In vivo, we demonstrated that LUZ-8F2-6B1 could provide protection against infection by four serotypes of DENV in a mouse model. In addition, the deletion of nine amino acids in the Fc region (LUZ-8F2-6B1-9del) completely abolished the antibody-dependent enhancement observed at lower doses of the antibody. Thus, LUZ-8F2-6B1 is a promising, safe, and effective agent for the prophylaxis and treatment of DENV infection.
- Published
- 2021