Safety and Immunogenicity of SARS-CoV-2 Self-Amplifying RNA Vaccine Expressing Anchored RBD: A Randomised, Observer-Blind, Phase 1 Study

Abstract

Background: 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.

Method: A phase 1 study of VLPCOV-01 was conducted at Medical Corporation Heishinkai OPHAC Hospital, Japan. 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 between February 16, 2022, and March 17, 2022. Solicited adverse events were collected up to 6 days post-administration. Interim immunogenicity analyses included SARS-CoV-2 IgG and neutralising antibody titres. Follow-up for safety and immunogenicity evaluation is ongoing. (The trial is registered: jRCT2051210164).

Findings: 92 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 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. Among elderly participants, IgG titres at 26 weeks post-vaccination with 3 µg VLPCOV-01 were 9865 (95% CI 4,396–22,138) compared to 4183 (95% CI 1,436–12,180) 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). 

Conclusions: VLPCOV-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.

Note:
Clinical Trial Registration Details: The trial is registered :jRCT205121016

Funding Information: Supported by AMED, Grant No. JP21nf0101627.

Declaration of Interests: M Komori, A Morey, K Ishimoto and K Matsuda are employees of VLP Therapeutics, Inc.; W Akahata is a board member, an employee and holds stocks in VLP Therapeutics, Inc. and is a management board member of VLP Therapeutics Japan, LLC; J F Smith and M Nakata are employees and hold stocks in VLP Therapeutics. Inc.; T Sekida, N Sato, K Kono and Y Kazami are employees of VLP Therapeutics Japan, LLC; T Hasunuma received a consultation fee from VLP Therapeutics Japan, LLC. for medical advice and consultation on clinical trial design; W Akahata and J F Smith are inventors on related vaccine patent. T Nogimori, H Ode, T Tamura, A Washizaki, Y Masuta, R Suzuki, T Fukuhara, Y Iwatani, and T Yamamoto has no conflict of interest.

Ethics Approval Statement: The study protocol was reviewed and approved by the Medical Corporation Heishinkai OPHAC Hospital institutional review board, and the trial was conducted at Medical Corporation Heishinkai OPHAC Hospital. No important changes to the methods were made following trial commencement. All participants provided written informed consent before enrolment.

Keywords: SARS-CoV-2, self-amplifying RNA vaccine, phase 1 study