Wang Shaoyan, Li Ruihua, Pan Xiaoyan, Wang Meirong, Wu Yan, Li Yaohui, Huang Xiaoyan, Zhu Rui, Wang Xiaolin, Zhang Yue, Yang Yilong, Zhang Jun, Xiao Gengfu, Zai Xiaodong, Xu Junjie, Chen Wei
Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, China.
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
NPJ Vaccines. 2025 Feb 22;10(1):37. doi: 10.1038/s41541-025-01090-4.
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.
拉沙病毒（LASV）属于沙粒病毒科，可引起人类严重出血热。尽管目前有许多针对拉沙热的候选疫苗，但尚无疫苗获批用于临床。前体糖蛋白复合物（GPC）以三聚体形式表达于病毒表面，是疫苗研发的主要靶点。然而，诱导产生针对LASV的有效中和抗体一直是一项重大挑战。在本研究中，我们设计并制备了一种LASV的预融合GPC三聚体抗原，命名为GPCv2。基于GPC的结构信息，我们通过将第328位氨基酸替换为脯氨酸并附加三聚化结构域进行修饰。这导致GPCv2以预融合三聚体形式高度表达，保留了重要的构象表位并刺激产生更高水平的中和抗体。此外，用GPCv2免疫可保护小鼠免受LASV假病毒攻击。另外，免疫组库测序显示，与单体组相比，三聚体组诱导的免疫克隆更趋同，且有其独特的V-J配对偏好。这些发现证明了GPCv2作为一种有效抗LASV疫苗的有前景的候选抗原的潜力。
