{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:39:16Z","timestamp":1785425956950,"version":"3.56.0"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002999","name":"Ministry of Health Welfare and Sport","doi-asserted-by":"publisher","award":["1006173-PDC19"],"award-info":[{"award-number":["1006173-PDC19"]}],"id":[{"id":"10.13039\/501100002999","id-type":"DOI","asserted-by":"publisher"}]},{"award":["1006173-PDC19"],"award-info":[{"award-number":["1006173-PDC19"]}],"id":[{"id":"https:\/\/ror.org\/041evnj42","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: The COVID-19 pandemic exposed critical gaps in pandemic preparedness and highlighted the need for vaccine platforms capable of rapid adaptation. Outer membrane vesicle (OMV)-based platforms utilizing vesicles derived from genetically detoxified Neisseria meningitidis serogroup B (Nm-nOMV) represent a promising plug-and-play approach. Methods: This Phase I, first-in-human, randomized, double-blind, placebo- and OMV-controlled trial, evaluated safety, tolerability, and immunogenicity of intranasally administered OMVs combined with SARS-CoV-2 Spike protein in healthy SARS-CoV-2 seropositive adults aged 18\u201355 years. Forty participants were enrolled across two cohorts: a low-dose cohort receiving 140 \u03bcg OMV\/70 \u03bcg Spike (OMV + Spike, n = 13; OMV alone, n= 3; Placebo, n = 5) and a high-dose cohort receiving 280 \u03bcg of OMV\/140 \u03bcg of Spike (OMV + Spike, n = 13; OMV alone, n = 3; Placebo, n = 3), administered on Days 1 and 22. Safety was assessed through adverse events, vital signs, laboratory parameters, ECG, and pulse oximetry. Immunogenicity was evaluated via systemic SARS-CoV-2 neutralizing antibodies, antigen-specific antibodies (IgG and IgA), and mucosal antibodies (IgA in nasal wash). Results: Intranasal administration of OMVs combined with SARS-CoV-2 Spike protein was safe, well-tolerated, and immunogenic. No serious adverse events were reported, and adverse events were predominantly mild and transient. Dose-dependent increases in systemic and mucosal immune responses were observed, with statistically significant enhanced serum IgG and nasal wash IgA antibodies in the high-dose group. Conclusions: The current clinical data confirm key aspects of the preclinical profile, which demonstrate the potential of the Nm-nOMV platform as a strong adjuvant for mucosal vaccines. These findings support the broader application of the Nm-nOMV vaccine platform in pandemic preparedness.<\/jats:p>","DOI":"10.3390\/vaccines14070575","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Randomized, Double-Blind, Placebo-Controlled Phase I Study to Evaluate the Safety, Tolerability, and Immunogenicity of an Outer Membrane Vesicle (OMV) Platform-Based Vaccine Administered Intranasally to Healthy Adults"],"prefix":"10.3390","volume":"14","author":[{"given":"Heleen","family":"Kraan","sequence":"first","affiliation":[{"name":"AdJane BV, Thijsseweg 11, 2629 JA Delft, The Netherlands"},{"name":"Intravacc BV, Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0977-8516","authenticated-orcid":false,"given":"Anne","family":"van der Geest","sequence":"additional","affiliation":[{"name":"Athena Institute, Vrije Universiteit, Boelelaan 1105, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8707-2266","authenticated-orcid":false,"given":"Dinja","family":"Oosterhoff","sequence":"additional","affiliation":[{"name":"Intravacc BV, Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corine","family":"Kruiswijk","sequence":"additional","affiliation":[{"name":"Intravacc BV, Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Soema","sequence":"additional","affiliation":[{"name":"Intravacc BV, Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/cei.13517","article-title":"Vaccines for COVID-19","volume":"202","author":"Tregoning","year":"2020","journal-title":"Clin. 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