{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:29Z","timestamp":1787028509792,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan","award":["18 2013-04-01"],"award-info":[{"award-number":["18 2013-04-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tuberculosis is a major global threat to human health. Since the widely used BCG vaccine is poorly effective in adults, there is a demand for the development of a new type of boost tuberculosis vaccine. We designed a novel intranasal tuberculosis vaccine candidate, TB\/FLU-04L, which is based on an attenuated influenza A virus vector encoding two mycobacterium antigens, Ag85A and ESAT-6. As tuberculosis is an airborne disease, the ability to induce mucosal immunity is one of the potential advantages of influenza vectors. Sequences of ESAT-6 and Ag85A antigens were inserted into the NS1 open reading frame of the influenza A virus to replace the deleted carboxyl part of the NS1 protein. The vector expressing chimeric NS1 protein appeared to be genetically stable and replication-deficient in mice and non-human primates. Intranasal immunization of C57BL\/6 mice or cynomolgus macaques with the TB\/FLU-04L vaccine candidate induced Mtb-specific Th1 immune response. Single TB\/FLU-04L immunization in mice showed commensurate levels of protection in comparison to BCG and significantly increased the protective effect of BCG when applied in a \u201cprime-boost\u201d scheme. Our findings show that intranasal immunization with the TB\/FLU-04L vaccine, which carries two mycobacterium antigens, is safe, and induces a protective immune response against virulent M. tuberculosis.<\/jats:p>","DOI":"10.3390\/ijms24087439","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T05:18:13Z","timestamp":1681795093000},"page":"7439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Preclinical Evaluation of TB\/FLU-04L\u2014An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3685-7068","authenticated-orcid":false,"given":"Anna-Polina","family":"Shurygina","sequence":"first","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Zabolotnykh","sequence":"additional","affiliation":[{"name":"Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation, 191036 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Vinogradova","sequence":"additional","affiliation":[{"name":"Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation, 191036 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berik","family":"Khairullin","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markhabat","family":"Kassenov","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainur","family":"Nurpeisova","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1310-3936","authenticated-orcid":false,"given":"Gulbanu","family":"Sarsenbayeva","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abylai","family":"Sansyzbay","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill","family":"Vasilyev","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna","family":"Buzitskaya","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Egorov","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Stukova","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022). 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