Optimization of an LNP-mRNA vaccine candidate targeting SARS-CoV-2 receptor-binding domain
Optimization of an LNP-mRNA vaccine candidate targeting SARS-CoV-2 receptor-binding domain
In 2020, two mRNA-based vaccines, encoding the full length of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, have been introduced for control of the coronavirus disease (COVID-19) pandemic1,2. However, reactogenicity, such as fever, caused by innate immune responses to the vaccine formulation remains to be improved. Here, we optimized a lipid nanoparticle (LNP)-based mRNA vaccine candidate, encoding the SARS-CoV-2 spike protein receptor-binding domain (LNP-mRNA-RBD), which showed improved immunogenicity by removing reactogenic materials from the vaccine formulation and protective potential against SARS-CoV-2 infection in cynomolgus macaques. LNP-mRNA-RBD induced robust antigen-specific B cells and follicular helper T cells in the BALB/c strain but not in the C57BL/6 strain; the two strains have contrasting abilities to induce type I interferon production by dendritic cells. Removal of reactogenic materials from original synthesized mRNA by HPLC reduced type I interferon (IFN) production by dendritic cells, which improved immunogenicity. Immunization of cynomolgus macaques with an LNP encapsulating HPLC-purified mRNA induced robust anti-RBD IgG in the plasma and in various mucosal areas, including airways, thereby conferring protection against SARS-CoV-2 infection. Therefore, fine-tuning the balance between the immunogenic and reactogenic activity of mRNA-based vaccine formulations may offer safer and more efficacious outcomes.
Imai Masaki、Kobiyama Kouji、Nakayama Misako、Hioki Kou、Yamayoshi Seiya、Tsuchida Jun、Suzuki Takashi、Temizoz Burcu、Itoh Yasushi、Takeshita Fumihiko、Kitagawa Yoshinori、Ishigaki Hirohito、Kawaoka Yoshihiro、Yamada Shinya、Watanabe Tokiko、Nguyen Cong Thanh、Iwatsuki-Horimoto Kiyoko、Niwa Takako、Ishii Ken J.、Ito Mutsumi、Negishi Hideo、Jounai Nao、Kiso Maki
Division of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of TokyoDivision of Vaccine Science, The Institute of Medical Science, The University of TokyoDivision of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical ScienceDivision of Vaccine Science, The Institute of Medical Science, The University of TokyoDivision of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of TokyoDivision of Vaccine Science, The Institute of Medical Science, The University of TokyoBiologics Division, Modality Research LaboratoriesDivision of Vaccine Science, The Institute of Medical Science, The University of TokyoDivision of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical ScienceBiologics Division, Vaccine Research LaboratoriesDivision of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical ScienceDivision of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical ScienceDivision of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of TokyoDivision of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of TokyoDivision of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of TokyoDivision of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical ScienceDivision of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of TokyoBiologics Division, Modality Research LaboratoriesDivision of Vaccine Science, The Institute of Medical Science, The University of TokyoDivision of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of TokyoDivision of Vaccine Science, The Institute of Medical Science, The University of TokyoBiologics Division, Vaccine Research LaboratoriesDivision of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo
预防医学生物科学现状、生物科学发展生物科学研究方法、生物科学研究技术
Imai Masaki,Kobiyama Kouji,Nakayama Misako,Hioki Kou,Yamayoshi Seiya,Tsuchida Jun,Suzuki Takashi,Temizoz Burcu,Itoh Yasushi,Takeshita Fumihiko,Kitagawa Yoshinori,Ishigaki Hirohito,Kawaoka Yoshihiro,Yamada Shinya,Watanabe Tokiko,Nguyen Cong Thanh,Iwatsuki-Horimoto Kiyoko,Niwa Takako,Ishii Ken J.,Ito Mutsumi,Negishi Hideo,Jounai Nao,Kiso Maki.Optimization of an LNP-mRNA vaccine candidate targeting SARS-CoV-2 receptor-binding domain[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.03.04.433852.点此复制
评论