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

Ryuta Uraki; Masaki Imai; Mutsumi Ito; Seiya Yamayoshi; Maki Kiso; Nao Jounai; Kazuki Miyaji; Kiyoko Iwatsuki-Horimoto; Fumihiko Takeshita; Yoshihiro Kawaoka

doi:10.1038/s41541-023-00800-0

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

NPJ Vaccines. 2024 Jan 2;9(1):4. doi: 10.1038/s41541-023-00800-0.

Authors

Ryuta Uraki^{1

2}, Masaki Imai^{1

2}, Mutsumi Ito¹, Seiya Yamayoshi^{1

2}, Maki Kiso¹, Nao Jounai³, Kazuki Miyaji³, Kiyoko Iwatsuki-Horimoto¹, Fumihiko Takeshita³, Yoshihiro Kawaoka^{4

5

6

7}

Affiliations

¹ Division of Virology, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
² The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, 162-8655, Japan.
³ Biologics Division, Vaccine Research Laboratories, Daiichi Sankyo Co., Ltd, Tokyo, 134-0081, Japan.
⁴ Division of Virology, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan. yoshihiro.kawaoka@wisc.edu.
⁵ The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, 162-8655, Japan. yoshihiro.kawaoka@wisc.edu.
⁶ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-, Madison, WI, 53711, USA. yoshihiro.kawaoka@wisc.edu.
⁷ The University of Tokyo, Pandemic Preparedness, Infection and Advanced Research Center, Tokyo, 162-8655, Japan. yoshihiro.kawaoka@wisc.edu.

Abstract

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.

Abstract

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