Publication date: May 23, 2025
The COVID-19 pandemic highlighted the need for innovative vaccine platforms that elicit durable immunity. Self-amplifying RNA (saRNA) vaccines offer rapid production and dose-sparing advantages over traditional mRNA platforms. In Uganda’s first SARS-CoV-2 vaccine trial (NCT04934111), we assessed the safety and immunogenicity of a saRNA vaccine encoding the SARS-CoV-2 spike (S) glycoprotein in seronegative and seropositive adults. This non-randomised phase 1 trial (December 2021-April 2022) enrolled 42 healthy adults (18-45 years), including 12 seronegative and 30 seropositive for SARS-CoV-2. Participants received two 5 μg doses of saRNA vaccine, four weeks apart. Reactogenicity was assessed using diary cards for seven days post-vaccination, and adverse events were monitored throughout the 24-week study. Binding and neutralising antibody levels were quantified using ELISA and pseudovirus neutralisation assays. The vaccine was well tolerated, with only mild-to-moderate adverse events, including fatigue, headache, and chills. No serious vaccine-related events occurred. Among seronegative participants, 91. 6% seroconverted after two doses (median S-IgG: 3695 ng/mL, p < 0. 001). In the seropositive participants, S-IgG rose modestly from 7496 to 11,028 ng/mL after the second dose. Neutralising titres increased modestly across WT, BA. 2, and A. 23. 1 variants, with no significant differences between groups. The saRNA SARS-CoV-2 vaccine was safe and immunogenic, inducing robust spike glycoprotein-specific antibody responses, particularly in seronegative participants. This trial demonstrates the potential of saRNA vaccines for broader use.
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| Concepts | Keywords |
|---|---|
| Headache | neutralising antibody responses |
| Healthy | phase 1 clinical trial |
| Nct04934111 | SARS-CoV-2 immunogenicity |
| Vaccine | spike-specific IgG antibodies |