{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T11:09:46Z","timestamp":1772449786922,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shenzhen Medical Research Special Fund Project","award":["A2304001"],"award-info":[{"award-number":["A2304001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130066"],"award-info":[{"award-number":["82130066"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Effective tuberculosis vaccines capable of inducing durable pulmonary immunity remain an unmet need. Mucosal vaccination strategies and rational antigen selection are increasingly recognized as critical for improving protection against aerosol Mycobacterium tuberculosis (Mtb) infection. Objective: The objective of this study was to establish an intranasal recombinant adeno-associated virus (rAAV) platform and evaluate SapM (Rv3310) as a mucosal TB vaccine antigen in mice. Methods: We established and optimized an rAAV production and purification platform suitable for intranasal immunization and applied it to deliver Mtb antigen SapM. Immunogenicity was assessed by lung mucosal T-cell responses (CD69\/CD103) and IFN-\u03b3 production in the lungs and spleen after mycobacterial antigen stimulation. Protective efficacy was evaluated after aerosol H37Rv challenge by quantifying pulmonary bacterial burden and lung pathology compared with vector controls and BCG. Results: rAAV6-SapM was successfully produced and efficiently transduced antigen-presenting cells without inducing phenotypic maturation. Intranasal immunization in mice induced mucosal T-cell responses in the lungs and increased expression of tissue residency-related markers (CD69 and CD103). It also elicited a Th1-biased cellular immune response characterized by enhanced IFN-\u03b3 production in both the lungs and spleen in response to mycobacterial antigen stimulation. Upon aerosol challenge with virulent Mtb H37Rv, rAAV6-SapM-immunized mice exhibited a significant reduction in pulmonary bacterial burden and attenuated lung pathology compared with vector-immunized controls. Conclusions: These findings provide proof-of-concept evidence that intranasal delivery of an AAV-based vaccine encoding SapM can induce antigen-responsive Th1 immunity and confer significant protection against early pulmonary TB, supporting further exploration of SapM as a vaccine antigen and AAV-based mucosal gene vaccination as a platform for TB vaccine development.<\/jats:p>","DOI":"10.3390\/vaccines14030224","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:24:34Z","timestamp":1772447074000},"page":"224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intranasal Vaccination with a Recombinant Adeno-Associated Virus Type 6 Encoding SapM Confers Protection Against Tuberculosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Chaonan","family":"Xing","sequence":"first","affiliation":[{"name":"College of Biological Sciences, China Agricultural University, Beijing 100193, China"},{"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenfei","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siwan","family":"Feng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningjian","family":"Cai","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siwei","family":"Mo","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1363-2328","authenticated-orcid":false,"given":"Yi","family":"Cai","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinchun","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyan","family":"Shi","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen 518060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). 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