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

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 SARS-CoV-2 is needed. Here, we report the immunogenic characteristics of self-amplifying RNA (saRNA) vaccine expressing the SARS-CoV-2 Spike (S) receptor binding domain (RBD), which is membrane-anchored by using 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.

Mai Komori, Takuto Nogimori, Amber L. Morey, Takashi Sekida, Keiko Ishimoto, Matthew R. Hassett, Yuji Matsuda, Hirotaka Ode, Tomokazu Tamura, Rigel Suzuki, Jeff Alexander, Yasutoshi Kido, Kenta Matsuda, Takasuke Fukuhara, Yasumasa Iwatani, Takuya Yamamoto, Jonathan F. Smith, Wataru Akahata