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

Author:

Komori MaiORCID,Nogimori TakutoORCID,Morey Amber L.ORCID,Sekida Takashi,Ishimoto KeikoORCID,Hassett Matthew R.,Masuta YujiORCID,Ode Hirotaka,Tamura TomokazuORCID,Suzuki Rigel,Alexander Jeff,Kido YasutoshiORCID,Matsuda Kenta,Fukuhara TakasukeORCID,Iwatani YasumasaORCID,Yamamoto TakuyaORCID,Smith Jonathan F.ORCID,Akahata WataruORCID

Abstract

AbstractSeveral 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.

Funder

Japan Agency for Medical Research and Development

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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