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

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.