Safety and immunogenicity of SARS-CoV-2 self-amplifying RNA vaccine expressing anchored RBD: a randomised, observer-blind, phase 1 study, Akahata et al.

Published: 24 July 2023| Version 3 | DOI: 10.17632/k7zf8893x2.3
Wataru Akahata, Takashi Sekida, Takuto Nogimori, Hirotaka Ode, Tomokazu Tamura, Kaoru Kono, Yoko Kazami, Ayaka Washizaki, Yuji Masuta, Rigel Suzuki, Kenta Matsuda, Mai Komori, Amber Morey, Keiko Ishimoto, Misako Nakata, Tomoko Hasunuma, Takasuke Fukuhara, Yasumasa Iwatani, Takuya Yamamoto, Jonathan Smith, Nobuaki Sato


VLPCOV-01 is a lipid nanoparticle-encapsulated self-amplifying RNA (saRNA) vaccine that expresses a membrane-anchored receptor-binding domain (RBD) derived from the SARS-CoV-2 spike protein. A phase 1 study of VLPCOV-01 is conducted (jRCT2051210164). Participants who had completed two doses of the BNT162b2 mRNA vaccine previously are randomised to receive one intramuscular vaccination of 0·3, 1·0, or 3·0 µg VLPCOV-01, 30 µg BNT162b2, or placebo. No serious adverse events have been reported. VLPCOV-01 induces robust IgG titres against RBD protein that are maintained up to 26 weeks in non-elderly participants, with geometric means ranging from 5037 (95% CI 1,272–19,940) at 0·3 µg to 12,873 (95% CI 937–17,686) at 3 µg, in comparison to 3,166 (95% CI 1,619–6,191) with 30 µg BNT162b2. Neutralising antibody titres against all variants of SARS-CoV-2 tested are induced. VLPCOV-01 is immunogenic following low dose administration. These findings support the potential for saRNA as a vaccine platform.



Vaccine, RNA, Adverse Event, Safety, Phase I Trials, COVID-19 Vaccine


Japan Agency for Medical Research and Development