saRNA vaccine expressing membrane-anchored RBD elicits broad and durable immunity against SARS-CoV-2 variants of concern

Mai Komori, Takuto Nogimori, Amber L. Morey, Takashi Sekida, Keiko Ishimoto, Matthew R. Hassett, Yuji Masuta, Hirotaka Ode, Tomokazu Tamura, Rigel Suzuki, Jeff Alexander, Yasutoshi Kido, Kenta Matsuda, Takasuke Fukuhara, Yasumasa Iwatani, Takuya Yamamoto (), Jonathan F. Smith () and Wataru Akahata ()
Additional contact information
Mai Komori: VLP Therapeutics
Takuto Nogimori: National Institutes of Biomedical Innovation, Health, and Nutrition
Amber L. Morey: VLP Therapeutics
Takashi Sekida: VLP Therapeutics Japan
Keiko Ishimoto: VLP Therapeutics
Matthew R. Hassett: VLP Therapeutics
Yuji Masuta: National Institutes of Biomedical Innovation, Health, and Nutrition
Hirotaka Ode: National Hospital Organization Nagoya Medical Center
Tomokazu Tamura: Hokkaido University
Rigel Suzuki: Hokkaido University
Jeff Alexander: VLP Therapeutics
Yasutoshi Kido: Osaka Metropolitan University
Kenta Matsuda: VLP Therapeutics
Takasuke Fukuhara: Hokkaido University
Yasumasa Iwatani: National Hospital Organization Nagoya Medical Center
Takuya Yamamoto: National Institutes of Biomedical Innovation, Health, and Nutrition
Jonathan F. Smith: VLP Therapeutics
Wataru Akahata: VLP Therapeutics Japan

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Several vaccines have been widely used to counteract the global pandemic caused by SARS-CoV-2. However, due to the rapid emergence of SARS-CoV-2 variants of concern (VOCs), further development of vaccines that confer broad and longer-lasting protection against emerging VOCs are needed. Here, we report the immunological characteristics of a self-amplifying RNA (saRNA) vaccine expressing the SARS-CoV-2 Spike (S) receptor binding domain (RBD), which is membrane-anchored by fusing with an N-terminal signal sequence and a C-terminal transmembrane domain (RBD-TM). Immunization with saRNA RBD-TM delivered in lipid nanoparticles (LNP) efficiently induces T-cell and B-cell responses in non-human primates (NHPs). In addition, immunized hamsters and NHPs are protected against SARS-CoV-2 challenge. Importantly, RBD-specific antibodies against VOCs are maintained for at least 12 months in NHPs. These findings suggest that this saRNA platform expressing RBD-TM will be a useful vaccine candidate inducing durable immunity against emerging SARS-CoV-2 strains.

Date: 2023
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DOI: 10.1038/s41467-023-38457-x

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