{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:31:28Z","timestamp":1784381488920,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Health and Social Care","award":["EP\/R013764\/1"],"award-info":[{"award-number":["EP\/R013764\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: 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\u2019s 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. Methods: This non-randomised phase 1 trial (December 2021\u2013April 2022) enrolled 42 healthy adults (18\u201345 years), including 12 seronegative and 30 seropositive for SARS-CoV-2. Participants received two 5 \u03bcg 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. Findings: 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 &lt; 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. Conclusion: 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.<\/jats:p>","DOI":"10.3390\/vaccines13060553","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T06:35:09Z","timestamp":1747982109000},"page":"553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Safety and Immunogenicity of a Modified Self-Amplifying Ribonucleic Acid (saRNA) Vaccine Encoding SARS-CoV-2 Spike Glycoprotein in SARS-CoV-2 Seronegative and Seropositive Ugandan Individuals"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2467-4037","authenticated-orcid":false,"given":"Jonathan","family":"Kitonsa","sequence":"first","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Serwanga","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"},{"name":"Uganda Virus Research Institute, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9044-1341","authenticated-orcid":false,"given":"Hannah M.","family":"Cheeseman","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Abaasa","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"},{"name":"Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane Frances","family":"Lunkuse","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7291-1693","authenticated-orcid":false,"given":"Eugene","family":"Ruzagira","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laban","family":"Kato","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Nambaziira","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald Kevin","family":"Oluka","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Gombe","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sembera","family":"Jackson","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6540-5522","authenticated-orcid":false,"given":"Joseph Katende","family":"Ssebwana","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon R.","family":"McFarlane","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-5201","authenticated-orcid":false,"given":"Benjamin F.","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.","family":"Shattock","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontiano","family":"Kaleebu","sequence":"additional","affiliation":[{"name":"Medical Research Council, Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda"},{"name":"Uganda Virus Research Institute, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020). Impact of COVID-19 on People\u2019s Livelihoods, Their Health and Our Food Systems, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100042","DOI":"10.1016\/j.sintl.2020.100042","article-title":"Global impacts of pre- and post-COVID-19 pandemic: Focus on socio-economic consequences","volume":"1","author":"Mishra","year":"2020","journal-title":"Sens. Int."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wise, J. (2023). COVID-19: WHO Declares End of Global Health Emergency, British Medical Journal Publishing Group.","DOI":"10.1136\/bmj.p1041"},{"key":"ref_4","unstructured":"WHO (2024, May 28). COVID-19 Dashboard. 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