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 F Smith; Nobuaki Sato

doi:10.1016/j.xcrm.2023.101134

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

Cell Rep Med. 2023 Aug 15;4(8):101134. doi: 10.1016/j.xcrm.2023.101134.

Authors

Wataru Akahata¹, Takashi Sekida², Takuto Nogimori³, Hirotaka Ode⁴, Tomokazu Tamura⁵, Kaoru Kono², Yoko Kazami², Ayaka Washizaki³, Yuji Masuta³, Rigel Suzuki⁵, Kenta Matsuda⁶, Mai Komori⁶, Amber L Morey⁶, Keiko Ishimoto⁶, Misako Nakata², Tomoko Hasunuma⁷, Takasuke Fukuhara⁸, Yasumasa Iwatani⁹, Takuya Yamamoto³, Jonathan F Smith⁶, Nobuaki Sato²

Affiliations

¹ VLP Therapeutics Japan, Inc., Marunouchi, Minato-ku, Tokyo 105-0003, Japan. Electronic address: wakahata@vlptherapeutics.com.
² VLP Therapeutics Japan, Inc., Marunouchi, Minato-ku, Tokyo 105-0003, Japan.
³ Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan.
⁴ Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi 460-0001, Japan.
⁵ Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
⁶ VLP Therapeutics, Inc., Gaithersburg, MD 20878, USA.
⁷ Department of Research, Kitasato University, Kitasato Institute Hospital, Minato-ku, Tokyo 108-0072, Japan.
⁸ Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
⁹ Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi 460-0001, Japan; Division of Basic Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.

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.

Keywords: COVID-19; RBD antigen; SARS-CoV-2; booster vaccine; immunogenicity; safety; self-amplifying RNA.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

BNT162 Vaccine
COVID-19 Vaccines / adverse effects
COVID-19* / prevention & control
Humans
Middle Aged
RNA
SARS-CoV-2 / genetics
Vaccines*
mRNA Vaccines

Substances

COVID-19 Vaccines
BNT162 Vaccine
RNA
Vaccines
mRNA Vaccines