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

• DOI: 10.1016/j.xcrm.2023.101134
• Publication Date: 2023-08-15T15:07:14Z
• Authors: 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 L. Morey; Keiko Ishimoto; Misako Nakata; Tomoko Hasunuma; Takasuke Fukuhara; Yasumasa Iwatani; Takuya Yamamoto; Jonathan F. Smith; Nobuaki Sato
• Keywords: 0301 basic medicine; Vaccines; 0303 health sciences; COVID-19 Vaccines; SARS-CoV-2; COVID-19; Middle Aged; 16. Peace & justice; Article; 3. Good health; 03 medical and health sciences; Humans; RNA; mRNA Vaccines; BNT162 Vaccine

SummaryBACKGROUNDVLPCOV-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.METHODSA 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).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.