An mRNA vaccine encoding the SARS-CoV-2 receptor-binding domain protects mice from various Omicron variants

作者：Ryuta Uraki, Masaki Imai, Mutsumi Ito, Seiya Yamayoshi, Maki Kiso, Nao Jounai, Kazuki Miyaji, Kiyoko Iwatsuki‐Horimoto, Fumihiko Takeshita, Yoshihiro Kawaoka · 发表于：npj Vaccines · 年份：2024 · DOI：10.1038/s41541-023-00800-0 · 被引用次数：15 · 研究领域：SARS-CoV-2 and COVID-19 Research、Animal Virus Infections Studies、RNA Interference and Gene Delivery

Here, we assessed the efficacy of a lipid nanoparticle-based mRNA vaccine candidate encoding the receptor-binding domain (LNP-mRNA-RBD) in mice. Mice immunized with LNP-mRNA-RBD based on the ancestral strain (ancestral-type LNP-mRNA-RBD) showed similar cellular responses against the ancestral strain and BA.5, but their neutralizing activity against BA.5 was lower than that against the ancestral strain. The ancestral-type LNP-mRNA-RBD protected mice from the ancestral strain or BA.5 challenge; however, its ability to reduce the viral burdens after BA.5 challenge was limited. In contrast, immunization with bivalent LNP-mRNA-RBD consisting of the ancestral-type and BA.4/5-type LNP-mRNA-RBD or monovalent BA.4/5-type LNP-mRNA-RBD elicited robust cellular responses, as well as high and moderate neutralizing titers against BA.5 and XBB.1.5, respectively. Furthermore, the vaccines containing BA.4/5-type LNP-mRNA-RBD remarkably reduced the viral burdens following BA.5 or XBB.1.5 challenge. Overall, our findings suggest that LNP-mRNA-RBD is effective against SARS-CoV-2 infection.