Development and evaluation of neutralizing antibodies for cross-protection against West Nile virus and Japanese encephalitis virus

Meng-Jie Yang , Hao-Ran Luo , Zhen-Yu Fan , Yu-Xiang Feng , Ning Wei , Bi-Bo Zhu , Jing Ye , Sheng-Bo Cao , You-Hui Si
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Abstract

Background

West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses, and is fatal for birds, chickens and other poultry. With no specific drugs or vaccines available, antibody-based therapy is a promising treatment. This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus.

Methods

Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology. The therapeutic efficacy of these antibodies was evaluated using a mouse model, and a humanized version of the monoclonal antibody was generated for potential human application.

Results

In this study, we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV. Their therapeutic effects against WNV were validated both in vivo and in vitro. Among these antibodies, C9-G11-F3 also exhibited cross-protective activity against JEV. We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans.

Conclusion

This study highlights the importance of neutralizing antibodies as a promising approach for protection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.

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抗西尼罗河病毒和日本脑炎病毒交叉保护中和抗体的研制与评价
背景西尼罗河病毒是一种严重的人畜共患病原体,可引起人和马的严重中枢神经系统症状,对鸟类、鸡和其他家禽致命。由于没有特效药或疫苗,基于抗体的治疗是一种很有前景的治疗方法。本研究旨在开发针对西尼罗河病毒的中和抗体,并评估其对日本脑炎病毒的交叉保护潜力。方法利用杂交瘤技术分离出抗WNV和JEV的单克隆抗体。使用小鼠模型评估这些抗体的治疗效果,并产生用于潜在人类应用的单克隆抗体的人源化版本。结果在本研究中,我们产生了8种对WNV具有中和活性的单克隆抗体。它们对WNV的治疗作用在体内和体外都得到了验证。在这些抗体中,C9-G11-F3也表现出对JEV的交叉保护活性。我们还对抗体进行了人源化,以确保其可用于人类的WNV感染治疗。结论本研究强调了中和抗体作为一种有前途的预防西尼罗河病毒感染的方法的重要性,并表明了其在开发治疗干预措施中的潜在效用。
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