Structure-guided design of a prefusion GPC trimer induces neutralizing responses against LASV.

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Tác giả: Wei Chen, Xiaoyan Huang, Ruihua Li, Yaohui Li, Xiaoyan Pan, Meirong Wang, Shaoyan Wang, Xiaolin Wang, Yan Wu, Gengfu Xiao, Junjie Xu, Yilong Yang, Xiaodong Zai, Jun Zhang, Yue Zhang, Rui Zhu

Ngôn ngữ: eng

Ký hiệu phân loại: 624.177 Structural design and specific structural elements

Thông tin xuất bản: England : NPJ vaccines , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 579485

Lassa virus (LASV) belongs to the Arenaviridae family and causes severe hemorrhagic fever in humans. Although many vaccine candidates for Lassa fever exist, no vaccines have been approved for clinical use currently. The precursor glycoprotein complex (GPC), which is expressed as a trimer on the viral surface, is the main target for vaccine development. However, it has been a significant challenge to elicit effective neutralizing antibodies against LASV. In this study, we designed and produced a prefusion GPC trimer antigen of LASV, named GPCv2. Based on the structural information of GPC, we made modifications by replacing the amino acid at position 328 with proline and appending the trimerization domain. This resulted in a highly expressed prefusion trimeric form of GPCv2 that retained important conformational epitopes and stimulated higher levels of neutralizing antibodies. Moreover, vaccination with GPCv2 protected mice from LASV pseudovirus challenge. Additionally, immune repertoire sequencing showed that the induced immune clones in the trimeric group were more convergent and has its own unique V-J pairing bias compared with monomeric group. These findings demonstrate the potential of GPCv2 as a promising candidate antigen for an effective vaccine against LASV.
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