Safety and immunogenicity of VLPCOV-02, a SARS-CoV-2 self-amplifying RNA vaccine with a modified base, 5-methylcytosine
Open accessAbstract
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.
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Recently, a study reported that 5% m5C-modified saRNA affords a functional construct as a SARS-CoV-2 booster in a phase 1 human safety study.
“Recently, a study reported that 5% m5C-modified saRNA affords a functional construct as a SARS-CoV-2 booster in a phase 1 human safety study47.”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [47]
The Introduction identifies VLPCOV-02 as a 5-methylcytosine–modified saRNA booster, and the Methods describe the reported phase 1 human safety study. The Conclusions report improved immune responses and a favorable safety profile, supporting the description of a functional construct. Our copy does not establish the claimed 5% modification level (searched: “5%” and “5% 5-methylcytosine modified saRNA”). (LLM, conf=0.85)
Experimental — accuracy not yet measuredHealthy participants vaccinated with LNPs containing 1, 3, 7.5, or 15 μg of 5% m5C saRNA had ~3-fold higher IgG titers at day 28.
“Healthy participants vaccinated with LNPs containing 1, 3, 7.5, or 15 μg of 5% m5C saRNA had ~3-fold higher IgG titers at day 28.”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [47]
The Results (Immunogenicity; page unavailable) report that IgG geometric mean titers rose from day 0 to day 28 at each dose, but the increases ranged from 2.3–5.1-fold in non-elderly participants and 2.3–2.9-fold in elderly participants, rather than being approximately threefold throughout. The Introduction and Discussion (Conclusions; pages unavailable) identify VLPCOV-02 as a 5-methylcytosine–modified, LNP-encapsulated saRNA vaccine, but the passages found do not establish the claimed 5% modification level. (LLM, conf=0.87)
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- Authors
- Aboshi, M., Matsuda, K., Kawakami, D., Kono, K., Kazami, Y., Sekida, T., Komori, M., Morey, A. L., Suga, S., Smith, J. F., Fukuhara, T., Iwatani, Y., Yamamoto, T., Sato, N., & Akahata, W.
- Affiliations
- VLP Therapeutics (United States) (US)
- National Hospital Organization (JP)
- Hokkaido University (JP)
- National Institute of Biomedical Innovation, Health and Nutrition (JP)
- Corresponding author
- Akahata, Wataru
- ORCID
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2024-02
- Volume
- 27
- Issue
- 2
- Pages
- 108964
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC10863314
- OpenAlex
- W4391113138
- Cited by
- 36
- References
- 19
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 8
- FWCI
- 12.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Japan Agency for Medical Research and Development (JP21nf0101627)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- self-amplifying RNA vaccine, SARS-CoV-2, 5-methylcytosine, modified nucleosides, lipid nanoparticle vaccine, COVID-19 vaccines, vaccine safety, immunogenicity, dose escalation, booster vaccination, receptor binding domain, reactogenicity
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