Wang Rong, Lu Jiansheng, Chen Lei, Yu Yunzhou, Yang Zhixin
Laboratory of Protein Engineering, Beijing Institute of Biotechnology, Beijing, China.
Laboratory of Protein Engineering, Beijing Institute of Biotechnology, Beijing, China.
Virology. 2021 Jun;558:49-56. doi: 10.1016/j.virol.2021.01.009. Epub 2021 Jan 22.
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.
在热带和亚热带国家，登革病毒（DENV）感染一直在增加；然而，我们仍然缺乏有效的治疗方法。在本研究中，我们旨在基于单克隆抗体6B1（具有抗DENV - 1、2和3活性）和8F2（具有抗DENV - 4活性）构建一种双特异性抗体（随后命名为LUZ - 8F2 - 6B1）。LUZ - 8F2 - 6B1通过与包膜蛋白结合，对四种血清型的登革病毒显示出强大的中和活性。在体内，我们证明LUZ - 8F2 - 6B1可以在小鼠模型中为抵抗四种血清型的登革病毒感染提供保护。此外，Fc区域九个氨基酸的缺失（LUZ - 8F2 - 6B1 - 9del）完全消除了在较低剂量抗体时观察到的抗体依赖性增强作用。因此，LUZ - 8F2 - 6B1是一种用于预防和治疗登革病毒感染的有前景、安全且有效的药物。
