Safety and immunogenicity of SARS-CoV-2 self-amplifying RNA vaccine expressing an anchored RBD: A randomized, observer-blind phase 1 study
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 Smith, Nobuaki Sato
Abstract
VLPCOV-01 is a lipid nanoparticle-encapsulated self-amplifying RNA (saRNA) vaccine that expresses a membrane-anchored receptor-binding domain (RBD) derived from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. A phase 1 study of VLPCOV-01 is conducted (jRCT2051210164). Participants who completed two doses of the BNT162b2 mRNA vaccine previously are randomized 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 immunoglobulin G (IgG) titers against the RBD protein that are maintained up to 26 weeks in non-elderly participants, with geometric means ranging from 5,037 (95% confidence interval [CI] 1,272-19,940) at 0.3 μg to 12,873 (95% CI 937-17,686) at 3 μg compared with 3,166 (95% CI 1,619-6,191) with 30 μg BNT162b2. Neutralizing antibody titers 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.