{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T01:19:40Z","timestamp":1787534380086,"version":"build-2736575974"},"reference-count":38,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"BPI France","award":["DOS0123291"],"award-info":[{"award-number":["DOS0123291"]}]},{"name":"BPI France","award":["DOS0123290"],"award-info":[{"award-number":["DOS0123290"]}]},{"name":"BPI France","award":["DOS0152140"],"award-info":[{"award-number":["DOS0152140"]}]},{"name":"BPI France","award":["DOS0152141"],"award-info":[{"award-number":["DOS0152141"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>OVX033 is a potential universal sarbecovirus vaccine candidate targeting the highly conserved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein. Preclinical studies have demonstrated cross-variant protection and favorable tolerability. This first-in-human trial evaluated the safety and immunogenicity of a single intramuscular dose of OVX033 in healthy adults (18\u201349 years).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this randomized, placebo-controlled, observer-blind, sequential, dose-escalation study, 48 participants, previously vaccinated with SARS-CoV-2 licensed vaccines, received either OVX033 (100\u2005\u00b5g, 250\u2005\u00b5g, or 500\u2005\u00b5g; n = 12 per cohort) or placebo (n = 12, 4 per cohort). Solicited reactogenicity was recorded for 7 days, unsolicited adverse events (AEs) for 28 days, and serious AEs (SAEs) for 6 months. Immunogenicity assessments included anti-N immunoglobulin G (IgG) and N-specific T-cell responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>OVX033 was safe and well-tolerated whatever the dose level. Injection site pain was the most common local reaction; fatigue, headache, and myalgia were the most frequent systemic symptoms. No severe reactogenicity, treatment-related SAEs, or safety signals were identified. OVX033 elicited a robust anamnestic anti-N IgG response, with titers peaking at day 29, and 4-fold rises versus baseline observed in 67%\u2013100% of vaccinees. Modest increases of N-specific IFN-\u03b3 CD4+ T-cell responses were measured on days 8 and 29 after vaccination, while CD8+ T-cell responses remained below the limit of quantification. No clear OVX033 dose effect was evidenced.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>OVX033 demonstrated a favorable safety profile and strong boosting of preexisting N-specific humoral immunity. Although a N-specific T-cell\u2013mediated immune response was achieved, it remained of limited amplitude. This limitation could be addressed by implementing a 2-dose regimen, or through the adjuvantation of the vaccine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trials Registration<\/jats:title>\n                    <jats:p>NCT06128382; EU-CT 2023-506396-94-00.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag409","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T11:50:23Z","timestamp":1786189823000},"source":"Crossref","is-referenced-by-count":0,"title":["Phase 1, First-in-Human, Randomized, Placebo-Controlled, Dose-Escalating Study to Evaluate OVX033, a Nucleocapsid-Based SARS-CoV-2 Candidate Vaccine"],"prefix":"10.1093","author":[{"given":"Odile","family":"Launay","sequence":"first","affiliation":[{"name":"Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Cochin , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Piat","sequence":"additional","affiliation":[{"name":"Osivax , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7681-9715","authenticated-orcid":false,"given":"Olivia","family":"Bonduelle","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm U1135, Centre d\u2019Immunologie et des Maladies Infectieuses\u2013Cimi-Paris , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4957-4038","authenticated-orcid":false,"given":"Jacques","family":"Bruhwyler","sequence":"additional","affiliation":[{"name":"Osivax , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5235-0868","authenticated-orcid":false,"given":"Liem Binh","family":"Luong","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Cochin , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9330-0637","authenticated-orcid":false,"given":"Mich\u00e8le","family":"Wokam","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm U1135, Centre d\u2019Immunologie et des Maladies Infectieuses\u2013Cimi-Paris , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessika","family":"Tourneur","sequence":"additional","affiliation":[{"name":"Osivax , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Moris","sequence":"additional","affiliation":[{"name":"Osivax , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Parfait","sequence":"additional","affiliation":[{"name":"Centre de Ressources Biologiques, H\u00f4pital Cochin Port-Royal , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Paques","sequence":"additional","affiliation":[{"name":"Osivax , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3958-6825","authenticated-orcid":false,"given":"Thalia Garcia","family":"T\u00e9llez","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Cochin , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Combadi\u00e8re","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Est Cr\u00e9teil, Inserm U955, Institut Mondor de Recherche Biom\u00e9dicale , Cr\u00e9teil ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Boissonnas","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Est Cr\u00e9teil, Inserm U955, Institut Mondor de Recherche Biom\u00e9dicale , Cr\u00e9teil ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1014-1858","authenticated-orcid":false,"given":"Alexandre","family":"Le Vert","sequence":"additional","affiliation":[{"name":"Osivax , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6564-4245","authenticated-orcid":false,"given":"Nicola","family":"Groth","sequence":"additional","affiliation":[{"name":"Osivax , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Nicolas","sequence":"additional","affiliation":[{"name":"Osivax , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2026082321115831700_jiag409-B1","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1016\/j.jinf.2020.07.002","article-title":"A comparison of mortality-related risk factors of COVID-19, SARS, and MERS: a systematic review and meta-analysis","volume":"81","author":"Lu","year":"2020","journal-title":"J Infect"},{"key":"2026082321115831700_jiag409-B2","doi-asserted-by":"crossref","first-page":"100967","DOI":"10.1016\/j.lanmic.2024.100967","article-title":"Prevalence and clinical relevance of viraemia in viral respiratory tract infections: a systematic review","volume":"6","author":"Hagman","year":"2025","journal-title":"Lancet Microbe"},{"key":"2026082321115831700_jiag409-B3","doi-asserted-by":"crossref","first-page":"106950","DOI":"10.1016\/j.ijid.2024.01.017","article-title":"Case fatality rates of COVID-19 during epidemic periods of variants of concern: a meta-analysis by continents","volume":"141","author":"Xia","year":"2024","journal-title":"Int J Infect Dis"},{"key":"2026082321115831700_jiag409-B4","first-page":"E311","article-title":"Case fatality rate of COVID-19: a systematic review and meta-analysis","volume":"62","author":"Alimohamadi","year":"2021","journal-title":"J Prev Med Hyg"},{"key":"2026082321115831700_jiag409-B5","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/s41392-023-01640-z","article-title":"The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"2026082321115831700_jiag409-B6","author":"World Health Organization"},{"key":"2026082321115831700_jiag409-B7","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1056\/NEJMp2211314","article-title":"A COVID-19 milestone attained\u2014a correlate of protection for vaccines","volume":"387","author":"Gilbert","year":"2022","journal-title":"N Engl J Med"},{"key":"2026082321115831700_jiag409-B8","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.cmi.2021.10.005","article-title":"Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review","volume":"28","author":"Fiolet","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"2026082321115831700_jiag409-B9","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.52225\/narra.v1i3.57","article-title":"Global acceptance and hesitancy of COVID-19 vaccination: a narrative review","volume":"1","author":"Hassan","year":"2021","journal-title":"Narra J"},{"key":"2026082321115831700_jiag409-B10","doi-asserted-by":"crossref","first-page":"106288","DOI":"10.1016\/j.jinf.2024.106288","article-title":"N-protein vaccine is effective against COVID-19: phase 3, randomized, double-blind, placebo-controlled clinical trial","volume":"89","author":"Rabdano","year":"2024","journal-title":"J Infect"},{"key":"2026082321115831700_jiag409-B11","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.cell.2020.08.017","article-title":"Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19","volume":"183","author":"Sekine","year":"2020","journal-title":"Cell"},{"key":"2026082321115831700_jiag409-B12","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1038\/s41467-023-38020-8","article-title":"Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion","volume":"14","author":"Eser","year":"2023","journal-title":"Nat Commun"},{"key":"2026082321115831700_jiag409-B13","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41590-021-01122-w","article-title":"The T cell immune response against SARS-CoV-2","volume":"23","author":"Moss","year":"2022","journal-title":"Nat Immunol"},{"key":"2026082321115831700_jiag409-B14","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41467-021-27674-x","article-title":"Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts","volume":"13","author":"Kundu","year":"2022","journal-title":"Nat Commun"},{"key":"2026082321115831700_jiag409-B15","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2021.01.007","article-title":"Adaptive immunity to SARS-CoV-2 and COVID-19","volume":"184","author":"Sette","year":"2021","journal-title":"Cell"},{"key":"2026082321115831700_jiag409-B16","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41586-020-2550-z","article-title":"SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls","volume":"584","author":"Le Bert","year":"2020","journal-title":"Nature"},{"key":"2026082321115831700_jiag409-B17","doi-asserted-by":"crossref","first-page":"4401","DOI":"10.1016\/j.cell.2021.06.029","article-title":"Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses","volume":"184","author":"Nathan","year":"2021","journal-title":"Cell"},{"key":"2026082321115831700_jiag409-B18","doi-asserted-by":"crossref","first-page":"e0135024","DOI":"10.1128\/jvi.01350-24","article-title":"Role of antiviral CD8+ T cell immunity to SARS-CoV-2 infection and vaccination","volume":"99","author":"Karl","year":"2025","journal-title":"J Virol"},{"key":"2026082321115831700_jiag409-B19","doi-asserted-by":"crossref","first-page":"eabp9770","DOI":"10.1126\/sciadv.abp9770","article-title":"Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity","volume":"8","author":"L\u00f3pez-Mu\u00f1oz","year":"2022","journal-title":"Sci Adv"},{"key":"2026082321115831700_jiag409-B20","doi-asserted-by":"crossref","first-page":"e162282","DOI":"10.1172\/JCI162282","article-title":"Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody","volume":"132","author":"Dangi","year":"2022","journal-title":"J Clin Invest"},{"key":"2026082321115831700_jiag409-B21","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/s43856-025-00894-8","article-title":"Serum anti-nucleocapsid antibody correlates of protection from SARS-CoV-2 re-infection regardless of symptoms or immune history","volume":"5","author":"Miyamoto","year":"2025","journal-title":"Commun Med"},{"key":"2026082321115831700_jiag409-B22","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.jmb.2012.12.017","article-title":"Arranged sevenfold: structural insights into the C-terminal oligomerization domain of human C4b-binding protein","volume":"425","author":"Hofmeyer","year":"2013","journal-title":"J Mol Biol"},{"key":"2026082321115831700_jiag409-B23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41541-019-0098-4","article-title":"OVX836 a recombinant nucleoprotein vaccine inducing cellular responses and protective efficacy against multiple influenza A subtypes","volume":"4","author":"Del Campo","year":"2019","journal-title":"NPJ Vaccines"},{"key":"2026082321115831700_jiag409-B24","doi-asserted-by":"crossref","first-page":"1188605","DOI":"10.3389\/fimmu.2023.1188605","article-title":"OVX033, a nucleocapsid-based vaccine candidate, provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model","volume":"14","author":"Primard","year":"2023","journal-title":"Front Immunol"},{"key":"2026082321115831700_jiag409-B25","article-title":"OVX033 nucleocapsid vaccine induces cross-reactive T cells and boosts memory in SARS-CoV-2 primed non-human primates","author":"Marlin","journal-title":"Commun Biol"},{"key":"2026082321115831700_jiag409-B26","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1001\/jama.2021.5374","article-title":"Reactogenicity following receipt of mRNA-based COVID-19 vaccines","volume":"325","author":"Chapin-Bardales","year":"2021","journal-title":"JAMA"},{"key":"2026082321115831700_jiag409-B27","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1080\/14760584.2022.2098719","article-title":"Comparing reactogenicity of COVID-19 vaccines: a systematic review and meta-analysis","volume":"21","author":"Sutton","year":"2022","journal-title":"Expert Rev Vaccines"},{"key":"2026082321115831700_jiag409-B28","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1080\/14760584.2024.2315089","article-title":"Comparing reactogenicity of COVID-19 vaccine boosters: a systematic review and meta-analysis","volume":"23","author":"San Francisco Ramos","year":"2024","journal-title":"Expert Rev Vaccines"},{"key":"2026082321115831700_jiag409-B29","doi-asserted-by":"crossref","first-page":"852904","DOI":"10.3389\/fimmu.2022.852904","article-title":"Randomized, double-blind, reference-controlled, phase 2a study evaluating the immunogenicity and safety of OVX836, a nucleoprotein-based influenza vaccine","volume":"13","author":"Leroux-Roels","year":"2022","journal-title":"Front Immunol"},{"key":"2026082321115831700_jiag409-B30","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/S1473-3099(23)00351-1","article-title":"Immunogenicity, safety, and preliminary efficacy evaluation of OVX836, a nucleoprotein-based universal influenza A vaccine candidate: a randomised, double-blind, placebo-controlled, phase 2a trial","volume":"23","author":"Leroux-Roels","year":"2023","journal-title":"Lancet Infect Dis"},{"key":"2026082321115831700_jiag409-B31","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.3390\/vaccines12121391","article-title":"Evaluation of safety, immunogenicity and cross-reactive immunity of OVX836, a nucleoprotein-based universal influenza vaccine, in older adults","volume":"12","author":"Jacobs","year":"2024","journal-title":"Vaccines"},{"key":"2026082321115831700_jiag409-B32","doi-asserted-by":"crossref","first-page":"558","DOI":"10.3390\/vaccines13060558","article-title":"Safety and immunogenicity of OVX836, a nucleoprotein-based universal influenza vaccine, co-administered with Fluarix Tetra, a seasonal hemagglutinin-based vaccine","volume":"13","author":"Groth","year":"2025","journal-title":"Vaccines"},{"key":"2026082321115831700_jiag409-B33","doi-asserted-by":"crossref","first-page":"127593","DOI":"10.1016\/j.vaccine.2025.127593","article-title":"From first infection to reinfection: comparing nucleocapsid antibody kinetics in vaccinated and unvaccinated adults","volume":"62","author":"Lindsey","year":"2025","journal-title":"Vaccine"},{"key":"2026082321115831700_jiag409-B34"},{"key":"2026082321115831700_jiag409-B35","doi-asserted-by":"crossref","first-page":"984642","DOI":"10.3389\/fimmu.2022.984642","article-title":"Harmonization and qualification of an IFN-\u03b3 enzyme-linked immunospot assay (ELISPOT) to measure influenza-specific cell-mediated immunity within the FLUCOP consortium","volume":"13","author":"Waerlop","year":"2022","journal-title":"Front Immunol"},{"key":"2026082321115831700_jiag409-B36","doi-asserted-by":"crossref","first-page":"982887","DOI":"10.3389\/fimmu.2022.982887","article-title":"Harmonization and qualification of intracellular cytokine staining to measure influenza-specific CD4+ T cell immunity within the FLUCOP consortium","volume":"13","author":"Begue","year":"2022","journal-title":"Front Immunol"},{"key":"2026082321115831700_jiag409-B37","doi-asserted-by":"crossref","first-page":"967","DOI":"10.3390\/v15040967","article-title":"SARS-CoV-2 reinfection and severity of the disease: a systematic review and meta-analysis","volume":"15","author":"Nguyen","year":"2023","journal-title":"Viruses"},{"key":"2026082321115831700_jiag409-B38","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3390\/vaccines12010100","article-title":"Safety and immunogenicity of the Convacell recombinant N protein COVID-19 vaccine","volume":"12","author":"Rabdano","year":"2024","journal-title":"Vaccines"}],"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\/jiag409\/70616928\/jiag409.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiag409\/70616928\/jiag409.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T01:12:04Z","timestamp":1787533924000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/advance-article\/doi\/10.1093\/infdis\/jiag409\/8759460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":38,"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiag409","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"article-number":"jiag409"}}