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A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates

Activation of nucleic acid sensing Toll-like receptors (TLRs) in B cells is involved in antiviral responses by promoting B cell activation and germinal center responses. In order to take advantage of this natural pathway for vaccine development, synthetic pathogen-like antigens (PLAs) constructed of...

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Detalles Bibliográficos
Autores principales: Guo, Chang, Peng, Yanan, Lin, Lin, Pan, Xiaoyan, Fang, Mengqi, Zhao, Yun, Bao, Keyan, Li, Runhan, Han, Jianbao, Chen, Jiaorong, Song, Tian-Zhang, Feng, Xiao-Li, Zhou, Yahong, Zhao, Gan, Zhang, Leike, Zheng, Yongtang, Zhu, Ping, Hang, Haiying, Zhang, Linqi, Hua, Zhaolin, Deng, Hongyu, Hou, Baidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536523/
https://www.ncbi.nlm.nih.gov/pubmed/34723223
http://dx.doi.org/10.1016/j.xcrm.2021.100448
Descripción
Sumario:Activation of nucleic acid sensing Toll-like receptors (TLRs) in B cells is involved in antiviral responses by promoting B cell activation and germinal center responses. In order to take advantage of this natural pathway for vaccine development, synthetic pathogen-like antigens (PLAs) constructed of multivalent antigens with encapsulated TLR ligands can be used to activate B cell antigen receptors and TLRs in a synergistic manner. Here we report a PLA-based coronavirus disease 2019 (COVID-19) vaccine candidate designed by combining a phage-derived virus-like particle carrying bacterial RNA as TLR ligands with the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein as the target antigen. This PLA-based vaccine candidate induces robust neutralizing antibodies in both mice and non-human primates (NHPs). Using a NHP infection model, we demonstrate that the viral clearance is accelerated in vaccinated animals. In addition, the PLA-based vaccine induces a T helper 1 (Th1)-oriented response and a durable memory, supporting its potential for further clinical development.