A phase I/II randomized, double-blinded, placebo-controlled trial of a self-amplifying Covid-19 mRNA vaccine
Open accessAbstract
Coronavirus disease-19 (Covid-19) pandemic have demonstrated the importantance of vaccines in disease prevention. Self-amplifying mRNA vaccines could be another option for disease prevention if demonstrated to be safe and immunogenic. Phase 1 of this randomized, double-blinded, placebo-controlled trial ( N = 42) assessed the safety, tolerability, and immunogenicity in healthy young and older adults of ascending levels of one-dose ARCT-021, a self-amplifying mRNA vaccine against Covid-19. Phase 2 ( N = 64) tested two-doses of ARCT-021 given 28 days apart. During phase 1, ARCT-021 was well tolerated up to one 7.5 μg dose and two 5.0 μg doses. Local solicited AEs, namely injection-site pain and tenderness were more common in ARCT-021vaccinated, while systemic solicited AEs, mainly fatigue, headache and myalgia were reported in 62.8% and 46.4% of ARCT-021 and placebo recipients, respectively. Seroconversion rate for anti-S IgG was 100% in all cohorts, except for the 1 μg one-dose in younger adults and the 7.5 μg one-dose in older adults. Anti-S IgG and neutralizing antibody titers showed a general increase with increasing dose, and overlapped with titers in Covid-19 convalescent patients. T-cell responses were also observed in response to stimulation with S-protein peptides. Taken collectively, ARCT-021 is immunogenic and has favorable safety profile for further development.
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Early saRNA vaccine trials showed lower efficacy and neutralizing antibody levels than mRNA vaccine trials.
“However, early saRNA vaccine trials showed lower efficacy and neutralizing antibody levels than mRNA vaccine trials11.”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [11]
The Discussion reports that neutralizing antibody titers for the saRNA vaccine ARCT-021 were low. It does not compare those titers with mRNA vaccine trials or report lower clinical efficacy for ARCT-021; the efficacy figure it mentions concerns a different saRNA vaccine, ARCT-154. No page number is available in our copy. (LLM, conf=0.84)
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“However, early saRNA vaccine trials showed lower efficacy and neutralizing antibody levels than mRNA vaccine trials 11 .”
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- Authors
- Low, J. G., de Alwis, R., Chen, S., Kalimuddin, S., Leong, Y. S., Mah, T. K. L., Yuen, N., Tan, H. C., Zhang, S. L., Sim, J. X. Y., Chan, Y. F. Z., Syenina, A., Yee, J. X., Ong, E. Z., Sekulovich, R., Sullivan, B. B., Lindert, K., Sullivan, S. M., Chivukula, P., Hughes, S. G., & Ooi, E. E.
- Affiliations
- SingHealth (SG)
- National University of Singapore (SG)
- Singapore General Hospital (SG)
- Arcturus Therapeutics (United States) (US)
- Corresponding author
- Hughes, Steven G.
- ORCID
- Venue
- npj Vaccines
- Published
- 2022-12-13
- Volume
- 7
- Issue
- 1
- Pages
- 161-161
- ISSN
- 2059-0105 (ISSN-L)
- PMC
- PMC9745278
- OpenAlex
- W4311822524
- Cited by
- 61
- References
- 26
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 19 · 2023: 16 · 2022: 2
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Vaccines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DR-NTU (Nanyang Technological University) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Keywords
- self-amplifying mRNA vaccine, COVID-19 vaccines, SARS-CoV-2 spike protein, vaccine safety, immunogenicity, dose escalation, neutralizing antibodies, T cell response, adverse events, older adults, young adults
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