Safety and immunogenicity of VLPCOV-02, a SARS-CoV-2 self-amplifying RNA vaccine with a modified base, 5-methylcytosine

Masayuki Aboshi; Kenta Matsuda; Daisuke Kawakami; Kaoru Kono; Yoko Kazami; Takashi Sekida; Mai Komori; Amber L Morey; Shigeru Suga; Jonathan F Smith; Takasuke Fukuhara; Yasumasa Iwatani; Takuya Yamamoto; Nobuaki Sato; Wataru Akahata

doi:10.1016/j.isci.2024.108964

Safety and immunogenicity of VLPCOV-02, a SARS-CoV-2 self-amplifying RNA vaccine with a modified base, 5-methylcytosine

iScience. 2024 Jan 22;27(2):108964. doi: 10.1016/j.isci.2024.108964. eCollection 2024 Feb 16.

Authors

Masayuki Aboshi¹, Kenta Matsuda², Daisuke Kawakami¹, Kaoru Kono¹, Yoko Kazami¹, Takashi Sekida¹, Mai Komori², Amber L Morey², Shigeru Suga³, Jonathan F Smith², Takasuke Fukuhara^{4

5}, Yasumasa Iwatani^{6

7}, Takuya Yamamoto⁸, Nobuaki Sato¹, Wataru Akahata¹

Affiliations

¹ VLP Therapeutics Japan, Inc., 1-16-4 Nishi-Shinbashi, Minato-ku, Tokyo 105-0003, Japan.
² VLP Therapeutics, Inc., Gaithersburg, MD 20878, USA.
³ National Hospital Organization, Mie National Hospital, Tsu, Mie 514-0125, Japan.
⁴ Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan.
⁵ Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
⁶ Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi 460-0001, Japan.
⁷ Division of Basic Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
⁸ Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan.

Abstract

Continuing emergence of variants of concern resulting in reduced SARS-CoV-2 vaccine efficacy necessitates additional prevention strategies. The structure of VLPCOV-01, a lipid nanoparticle-encapsulated, self-amplifying RNA COVID-19 vaccine with a comparable immune response to BNT162b2, was revised by incorporating a modified base, 5-methylcytosine, to reduce reactogenicity, and an updated receptor-binding domain derived from the Brazil (gamma) variant. Interim analyses of a phase 1 dose-escalation booster vaccination study with the resulting construct, VLPCOV-02, in healthy, previously vaccinated Japanese individuals (N = 96) are reported (jRCT2051230005). A dose-related increase in solicited local and systemic adverse events was observed, which were generally rated mild or moderate. The most commonly occurring events were tenderness, pain, fatigue, and myalgia. Serum SARS-CoV-2 immunoglobulin titers increased during the 4 weeks post-immunization. VLPCOV-02 demonstrated a favorable safety profile compared with VLPCOV-01, with reduced adverse events and fewer fever events at an equivalent dose. These findings support further study of VLPCOV-02.

Keywords: Immunology; Virology.