A universal design of restructured dimer antigens: Development of a superior vaccine against the paramyxovirus in transgenic rice
文献类型： 外文期刊
作者： Ma, Fanshu 1 ; Xu, Qianru 6 ; Wang, Aiping 1 ; Yang, Daichang 7 ; Li, Qingmei 8 ; Guo, Junqing 8 ; Zhang, Longxian 1 ; Ou, Jiquan 1 ; Li, Rui 8 ; Yin, Heng 9 ; Li, Kunpeng 9 ; Wang, Li 8 ; Wang, Yanan 8 ; Zhao, Xiangyue 8 ; Niu, Xiangxiang 1 ; Zhang, Shenli 1 ; Li, Xueyang 1 ; Chai, Shujun 8 ; Zhang, Erqin 1 ; Rao, Zihe 10 ; Zhang, Gaiping 1 ;
作者机构： 1.Henan Agr Univ, Coll Vet Med, Int Joint Res Ctr Natl Anim Immunol, Zhengzhou 450046, Peoples R China
2.Peking Univ, Sch Adv Agr Sci, Beijing 100871, Peoples R China
3.Longhu Lab Adv Immunol, Zhengzhou 450046, Peoples R China
4.Zhengzhou Univ, Coll Life Sci, Zhengzhou 450001, Peoples R China
5.Chinese Acad Sci, Suzhou Inst Nanotech & Nanob, Key Lab Nanobio Interface, Div Nanobiomed, Suzhou 215123, Peoples R China
6.Henan Univ, Sch Basic Med Sci, Kaifeng 475004, Peoples R China
7.Wuhan Univ, Coll Life Sci, State Key Lab Hybrid Rice, Wuhan 430074, Peoples R China
8.Henan Acad Agr Sci, Key Lab Anim Immunol, Zhengzhou 450002, Peoples R China
9.Wuhan Healthgen Biotechnol Corp, Wuhan 430074, Peoples R China
10.Tsinghua Univ, Sch Life Sci, Lab Struct Biol, Beijing 100084, Peoples R China
11.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China
关键词： structural vaccine; transgenic rice; BCR; paramyxovirus
期刊名称：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA （ 影响因子：11.1； 五年影响因子：12.0 ）
ISSN： 0027-8424
年卷期： 2024 年 121 卷 4 期
页码：
收录情况： SCI
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.
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