A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III.

Autor: Dan Hu, Zhongyu Zhu, Shun Li, Yongqiang Deng, Yanling Wu, Nana Zhang, Vinita Puri, Chunyu Wang, Peng Zou, Cheng Lei, Xiaolong Tian, Yulu Wang, Qi Zhao, Wei Li, Ponraj Prabakaran, Yang Feng, Jane Cardosa, Chengfeng Qin, Xiaohui Zhou, Dimiter S Dimitrov, Tianlei Ying
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS Pathogens, Vol 15, Iss 6, p e1007836 (2019)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1007836
Popis: Dengue is the most widespread vector-borne viral disease caused by dengue virus (DENV) for which there are no safe, effective drugs approved for clinical use. Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Immunogenetic analysis indicated that m366.6 is a germline-like mAb with very few somatic mutations from the closest VH and Vλ germline genes. Importantly, we demonstrated that it potently neutralized DENV both in vitro and in the mouse models of DENV infection without detectable antibody-dependent enhancement (ADE) effect. The epitope of m366.6 was mapped to the highly conserved regions on DIII, which may guide the design of effective dengue vaccine immunogens. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate.
Databáze: Directory of Open Access Journals
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