A universal design of restructured dimer antigens: Development of a superior vaccine against the paramyxovirus in transgenic rice

• 成果类型: Article
• 署名作者: Ma, Fanshu; Xu, Qianru; Wang, Aiping; Yang, Daichang; Li, Qingmei; Guo, Junqing; Zhang, Longxian; Ou, Jiquan; Li, Rui; Yin, Heng; Li, Kunpeng; Wang, Li; Wang, Yanan; Zhao, Xiangyue; Niu, Xiangxiang; Zhang, Shenli; Li, Xueyang; Chai, Shujun; Zhang, Erqin; Rao, Zihe; Zhang, Gaiping
• 署名单位: Henan Agricultural University; Peking University; Longhu Laboratory; Zhengzhou University; Chinese Academy of Sciences; Henan University; Wuhan University; Henan Academy of Agricultural Sciences; Tsinghua University; Tsinghua University; Tsinghua University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14714
• DOI: 10.1073/pnas.2305745121
• 发表日期: 2024-01-23
• 关键词: newcastle-disease virus; hemagglutinin-neuraminidase protein; glycoprotein; immunogenicity; immunization; expression; particles; responses

摘要

The development of vaccines, which induce effective immune responses while ensuring safety and affordability, remains a substantial challenge. In this study, we proposed a vaccine model of a restructured head-to-tail dimer to efficiently stimulate B cell response. We also demonstrate the feasibility of using this model to develop a paramyxovirus vaccine through a low-cost rice endosperm expression system. Crystal structure and small-angle X-ray scattering data showed that the restructured hemagglutinin- neuraminidase (HN) formed tetramers with fully exposed quadruple receptor binding domains and neutralizing epitopes. In comparison with the original HN antigen and three traditional commercial whole virus vaccines, the restructured HN facilitated critical epitope exposure and initiated a faster and more potent immune response. Two-dose immunization with 0.5 mu g of the restructured antigen (equivalent to one-127th of a rice grain) and one-dose with 5 mu g completely protected chickens against a lethal challenge of the virus. These results demonstrate that the restructured HN from transgenic rice seeds is safe, effective, low-dose useful, and inexpensive. We provide a plant platform and a simple restructured model for highly effective vaccine development.