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

Abstract

BACKGROUNDVLPCOV–01 is a lipid nanoparticle-encapsulated self–amplifying (sa) RNA vaccine that expresses a membrane-anchored receptor–binding domain (RBD) derived from the SARS–CoV–2 spike protein.METHODSA phase 1 study of VLPCOV–01 was conducted at Medical Corporation Heishinkai OPHAC Hospital, Japan. The investigational vaccines were administered to participants, between February 16, 2022, and March 17, 2022. Participants aged 18 to 55 or ≥65 years who had completed two doses of the BNT162b2 mRNA vaccine 6 to 12 months previously were randomised to receive one intramuscular vaccination of 0·3, 1·0, or 3·0 µg VLPCOV–01, 30 µg BNT162b2, or placebo. Solicited adverse events were collected up to 6 days post–administration, with follow–up on all adverse events until week 4. Interim immunogenicity analyses following data cutoff at day 29 included SARS-CoV-2 IgG and neutralising antibody titres. (The trial is registered: jRCT2051210164).FINDINGS92 healthy adults were enrolled, with 60 participants receiving VLPCOV–01. No serious adverse events were reported up to 26 weeks, and no prespecified trial-halting events were met. VLPCOV-01 induced robust IgG titres against SARS-CoV-2 RBD protein that were maintained up to 26 weeks in non-elderly participants, with geometric means ranging from 5037 (95% CI 1272–19,940) at 0·3 µg to 12,873 (95% CI 937–17,686) at 3 µg, in comparison to 3166 (95% CI 1619–6191) with 30 µg BNT162b2. Among elderly participants, IgG titres at 26 weeks post-vaccination with 3 µg VLPCOV–01 were 9865 (95% CI 4396–22138) compared to 4183 (95% CI 1436–12180) following vaccination with 30 µg BNT162b2. Pseudovirus–Neutralising antibody responses were observed against multiple SARS–CoV–2 variants and strongly correlated with anti–SARS–CoV–2 IgG (r=0·950, p<0·001).INTERPRETATIONVLPCOV–01 is immunogenic following low dose administration, with anti-SARS–CoV–2 immune responses comparable to BNT162b2. These findings support further development of VLPCOV–01 as a COVID–19 booster vaccine and the potential for saRNA vectors as a vaccine platform.FUNDINGSupported by AMED, Grant No. JP21nf0101627.