{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:43:25Z","timestamp":1785437005940,"version":"3.56.0"},"reference-count":60,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF) of Korea","doi-asserted-by":"publisher","award":["RS-2024-00442345"],"award-info":[{"award-number":["RS-2024-00442345"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2024-00442345"],"award-info":[{"award-number":["RS-2024-00442345"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Technology R&D Project","doi-asserted-by":"publisher","award":["RS-2024-00335889"],"award-info":[{"award-number":["RS-2024-00335889"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00fdzyk40","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministry of Health & Welfare, Republic of Korea"},{"id":[{"id":"https:\/\/ror.org\/00vxgjw72","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through the interaction between the spike protein receptor-binding domain (RBD) and the human angiotensin-converting enzyme 2 (hACE2) receptor, which is expressed on epithelial cells in various tissues, including the respiratory tract. Therefore, mucosal immunity in the respiratory tract plays a key role in protection against viral infection. Previously, we demonstrated that intranasal administration of antigens (Ags) conjugated with the M cell-targeting peptide Co4B enhances both mucosal and systemic immune responses. That conjugation with human \u03b2-defensin 2 (HBD2) increases neutralizing antibody (Ab) responses. Methods: A recombinant antigen conjugate incorporating both Co4B and HBD2 was designed to enhance immunogenicity. Its immunogenicity was evaluated in mice following intranasal immunization. Antigen-specific antibody responses were measured in serum and bronchoalveolar lavage fluid. T-cell responses were evaluated in lungs and spleens. Protective efficacy was assessed using SARS-CoV-2-susceptible hACE2 knock-in mice. Results: Ag-specific Ab levels increased in both serum and bronchoalveolar lavage fluid of mice immunized intranasally with the conjugate. Especially, T-cell responses were significantly enhanced in the lungs and spleens of immunized hACE2 knock-in mice. In challenge experiments, intranasal administration of the conjugate reduced viral load. Moreover, Siglec F was identified as a potential receptor for Co4B, a previously uncharacterized M cell-targeting ligand. Conclusions: A recombinant viral Ag containing Co4B and HBD2 induces virus-specific humoral and cellular immune responses. Although further optimization of the vaccine formulation and administration strategy is needed, this conjugate shows potential as a platform for improving mucosal and systemic immunity.<\/jats:p>","DOI":"10.3390\/vaccines14050421","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T09:03:37Z","timestamp":1778144617000},"page":"421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mucosal Delivery of Recombinant SARS-CoV-2 Spike Receptor-Binding Domain Antigen Containing Immune-Stimulating Peptides Induces Protective Immune Responses Against Viral Infection in huACE2 Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9847-6933","authenticated-orcid":false,"given":"Byeol-Hee","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, Republic of Korea"},{"name":"Korea Research Institute for Veterinary Biologics, Iksan 54531, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3615-0628","authenticated-orcid":false,"given":"Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-4224","authenticated-orcid":false,"given":"Yong-Suk","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, Republic of Korea"},{"name":"Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2002083","DOI":"10.1080\/21645515.2021.2002083","article-title":"A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson & Johnson","volume":"18","author":"Patel","year":"2022","journal-title":"Hum. 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