{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:13:09Z","timestamp":1788401589877,"version":"build-2803163510"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016302","name":"Coalition for Epidemic Preparedness Innovations","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016302","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health and Medical Research Council of Australia"},{"DOI":"10.13039\/501100003550","name":"Queensland Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003550","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A coronavirus disease 2019 (COVID-19) subunit vaccine developed with the molecular clamp platform was among the first to enter clinical trials in 2020. While the vaccine was well suited to large-scale manufacture and demonstrated a favorable safety and immunogenicity profile, it did not progress into further clinical testing due to the human immunodeficiency virus 1 (HIV-1)\u2013derived sequence in the molecular clamp, interfering with certain point-of-care HIV-1 diagnostic tests. A second-generation molecular clamp (MC2) has since been developed. Here, we describe a phase I clinical trial of an MC2-stabilized severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike subunit vaccine, UQSC2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A phase I, double-blind, active comparator-controlled trial was conducted in Australia (ClinicalTrials.gov NCT05775887). Healthy adults (aged 18\u201350 years), who had previously received \u22653 doses of an approved messenger RNA SARS-CoV-2 vaccine, received a single booster dose of either UQSC2 or the approved comparator NVX-CoV2373 (Nuvaxovid; Novavax) (n = 70; 35 per group). Safety, humoral immunogenicity (including against virus variants), and cellular immunogenicity were assessed through day 183. Cases of confirmed coronavirus disease 2019 (COVID-19) infection during the study were also examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both vaccines were equally well tolerated and elicited comparable increases in neutralizing humoral responses against the vaccine-matched prototypic, Wuhan strain of SARS-CoV-2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>UQSC2 was as well tolerated as the authorized comparator vaccine and produced an equally robust boost in neutralizing immune response. These findings support the effectiveness of the MC2 platform in producing vaccines against newly emerging variants of SARS-CoV-2 and other respiratory viruses, as well as the platform's potential use in emergency response to novel viruses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf568","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T12:35:58Z","timestamp":1762778158000},"page":"e373-e382","source":"Crossref","is-referenced-by-count":2,"title":["Safety and Immunogenicity of a Severe Acute Respiratory Syndrome Coronavirus 2 Spike Subunit Vaccine Stabilized in the Prefusion Conformation by a Second-Generation Molecular Clamp and Evaluated in Adults Aged 18\u201355 Years: A Randomized, Double-Blind, Active Comparator, Phase I Trial"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8636-5067","authenticated-orcid":false,"given":"Keith J","family":"Chappell","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"Australian Infectious Diseases Research Centre, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3754-2642","authenticated-orcid":false,"given":"Francesca L","family":"Mordant","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Parkville, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6640-3377","authenticated-orcid":false,"given":"Alberto A","family":"Amarilla","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3205-4970","authenticated-orcid":false,"given":"Naphak","family":"Modhiran","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0933-3998","authenticated-orcid":false,"given":"Julia A","family":"Lackenby","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noushin","family":"Jaberolansar","sequence":"additional","affiliation":[{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Kienzle","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varsha","family":"Kommajosyula","sequence":"additional","affiliation":[{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Tardiota","sequence":"additional","affiliation":[{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1983-8642","authenticated-orcid":false,"given":"Jillian K","family":"Bennet","sequence":"additional","affiliation":[{"name":"Independent consultant , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3374-6007","authenticated-orcid":false,"given":"Christina L","family":"Henderson","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2660-1424","authenticated-orcid":false,"given":"Rhiannon L","family":"Dalrymple","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4982-193X","authenticated-orcid":false,"given":"Justin","family":"Goh","sequence":"additional","affiliation":[{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kym","family":"Hoger","sequence":"additional","affiliation":[{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Gillard","sequence":"additional","affiliation":[{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5154-6017","authenticated-orcid":false,"given":"Martina L","family":"Jones","sequence":"additional","affiliation":[{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Hughes","sequence":"additional","affiliation":[{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3289-2195","authenticated-orcid":false,"given":"Ben","family":"Hughes","sequence":"additional","affiliation":[{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Barnes","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C","family":"Reading","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Parkville, Victoria ,","place":["Australia"]},{"name":"WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charani","family":"Ranasinghe","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University , Canberra, Australian Capital Territory ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanta","family":"Subbarao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Parkville, Victoria ,","place":["Australia"]},{"name":"WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1987-2020","authenticated-orcid":false,"given":"Trent P","family":"Munro","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R","family":"Young","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"Australian Infectious Diseases Research Centre, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Watterson","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]},{"name":"Australian Infectious Diseases Research Centre, The University of Queensland , St Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"2026031304544449600_jiaf568-B1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1080\/14760584.2022.2042257","article-title":"Clinical development and approval of COVID-19 vaccines","volume":"21","author":"Kalinke","year":"2022","journal-title":"Expert Rev Vaccines"},{"key":"2026031304544449600_jiaf568-B2","doi-asserted-by":"crossref","first-page":"e936523","DOI":"10.12659\/MSM.936523","article-title":"Editorial: first approval of the protein-based adjuvanted Nuvaxovid (NVX-CoV2373) Novavax vaccine for SARS-CoV-2 could increase vaccine uptake and provide immune protection from viral variants","volume":"28","author":"Parums","year":"2022","journal-title":"Med Sci Monit"},{"key":"2026031304544449600_jiaf568-B3","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/s41467-020-20653-8","article-title":"SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice","volume":"12","author":"Tian","year":"2021","journal-title":"Nat Commun"},{"key":"2026031304544449600_jiaf568-B4","doi-asserted-by":"crossref","first-page":"592370","DOI":"10.3389\/fimmu.2020.592370","article-title":"Rapid response subunit vaccine design in the absence of structural information","volume":"11","author":"Wijesundara","year":"2020","journal-title":"Front Immunol"},{"key":"2026031304544449600_jiaf568-B5","doi-asserted-by":"crossref","first-page":"963023","DOI":"10.3389\/fimmu.2022.963023","article-title":"A platform technology for generating subunit vaccines against diverse viral pathogens","volume":"13","author":"Young","year":"2022","journal-title":"Front Immunol"},{"key":"2026031304544449600_jiaf568-B6","doi-asserted-by":"crossref","first-page":"e1013312","DOI":"10.1371\/journal.ppat.1013312","article-title":"A second-generation molecular clamp stabilised bivalent candidate vaccine for protection against diseases caused by respiratory syncytial virus and human metapneumovirus","volume":"21","author":"Young","year":"2025","journal-title":"PLoS Pathog"},{"key":"2026031304544449600_jiaf568-B7","doi-asserted-by":"crossref","first-page":"e1269","DOI":"10.1002\/cti2.1269","article-title":"Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2","volume":"10","author":"Watterson","year":"2021","journal-title":"Clin Transl Immunol"},{"key":"2026031304544449600_jiaf568-B8","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/S1473-3099(21)00200-0","article-title":"Safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2: a randomised, double-blind, placebo-controlled, phase 1 trial","volume":"21","author":"Chappell","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"2026031304544449600_jiaf568-B9","doi-asserted-by":"crossref","first-page":"104842","DOI":"10.1016\/j.ebiom.2023.104842","article-title":"Long-term safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2 in adults aged 18\u201355 years or \u226556 years: 12-month results from a randomised, double-blind, placebo-controlled, phase 1 trial","volume":"97","author":"Chappell","year":"2023","journal-title":"EBioMedicine"},{"key":"2026031304544449600_jiaf568-B10","doi-asserted-by":"crossref","first-page":"459","DOI":"10.5694\/mja2.50569","article-title":"Isolation and rapid sharing of the 2019 novel coronavirus (SARS-CoV-2) from the first patient diagnosed with COVID-19 in Australia","volume":"212","author":"Caly","year":"2020","journal-title":"Med J Aust"},{"key":"2026031304544449600_jiaf568-B11","doi-asserted-by":"crossref","first-page":"625136","DOI":"10.3389\/fmicb.2021.625136","article-title":"An optimized high-throughput immuno-plaque assay for SARS-CoV-2","volume":"12","author":"Amarilla","year":"2021","journal-title":"Front Microbiol"},{"key":"2026031304544449600_jiaf568-B12","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/S1473-3099(22)00320-6","article-title":"Global impact of the first year of COVID-19 vaccination: a mathematical modelling study","volume":"22","author":"Watson","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"2026031304544449600_jiaf568-B13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.idc.2022.11.001","article-title":"Epidemiology and clinical presentation of COVID-19 in older adults","volume":"37","author":"Abul","year":"2023","journal-title":"Infect Dis Clin North Am"},{"key":"2026031304544449600_jiaf568-B14","author":"Food_and_Drug_Administration"},{"key":"2026031304544449600_jiaf568-B15","author":"European_Medicines_Agency"},{"key":"2026031304544449600_jiaf568-B16","doi-asserted-by":"crossref","first-page":"E7348","DOI":"10.1073\/pnas.1707304114","article-title":"Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen","volume":"114","author":"Pallesen","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026031304544449600_jiaf568-B17","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41541-021-00369-6","article-title":"Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action","volume":"6","author":"Heinz","year":"2021","journal-title":"NPJ Vaccines"},{"key":"2026031304544449600_jiaf568-B18","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N Engl J Med"},{"key":"2026031304544449600_jiaf568-B19","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N Engl J Med"},{"key":"2026031304544449600_jiaf568-B20","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1056\/NEJMoa2107659","article-title":"Safety and efficacy of NVX-CoV2373 COVID-19 vaccine","volume":"385","author":"Heath","year":"2021","journal-title":"N Engl J Med"},{"key":"2026031304544449600_jiaf568-B21","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1056\/NEJMoa2105290","article-title":"Phase 3 safety and efficacy of AZD1222 (ChAdOx1 nCoV-19) COVID-19 vaccine","volume":"385","author":"Falsey","year":"2021","journal-title":"N Engl J Med"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaf568\/65492611\/jiaf568.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/233\/2\/e373\/65492611\/jiaf568.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/233\/2\/e373\/65492611\/jiaf568.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:56:37Z","timestamp":1773392197000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/233\/2\/e373\/8341580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":21,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,11,25]]},"published-print":{"date-parts":[[2026,2,18]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaf568","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,2,15]]},"published":{"date-parts":[[2025,11,25]]}}}