{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T18:13:27Z","timestamp":1778004807994,"version":"3.51.4"},"reference-count":80,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education and Science of Russia","award":["14.N08.11.0192"],"award-info":[{"award-number":["14.N08.11.0192"]}]},{"name":"Ministry of Health of Russia","award":["125020501441-9"],"award-info":[{"award-number":["125020501441-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Tuberculosis (TB) remains the leading cause of death from a single infectious agent worldwide. In line with the World Health Organization\u2019s (WHO) goal to end TB by 2035, the rapid development and clinical implementation of new, effective vaccines is urgently needed. To support global TB control efforts, we developed a novel candidate subunit multistage vaccine. Methods: This vaccine incorporates multiple Mycobacterium tuberculosis antigens expressed during both dormant and active stages of infection, fused into a single recombinant protein (ESAT6-CFP10-Ag85A-Rv2660c-Rv1813c). The antigen was encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles along with the pattern recognition receptor (PRR) agonists monophosphoryl lipid A (MPLA) and muramyl dipeptide (MDP), which function as adjuvants. Results: Using a mixed intramuscular\/nasal prime-boost regimen, the vaccine elicited a mixed Th1\/Th17 cell-mediated immune response, as well as a robust humoral response characterized by sustained systemic IgG (lasting at least one year) and prominent local secretory IgA. The vaccine demonstrated protective efficacy as a prophylactic booster following BCG priming in both murine and guinea pig models and was also effective in a therapeutic setting in a murine infection model. Conclusions: The results of this study provide empirical evidence that multistage tuberculosis vaccines represent a promising strategy for achieving global TB control.<\/jats:p>","DOI":"10.3390\/vaccines14010005","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T16:19:26Z","timestamp":1766420366000},"page":"5","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Multistage Subunit Mycobacterium tuberculosis Nanoparticle Vaccine Confers Protection Against Experimental Infection in Prophylactic and Therapeutic Regimens"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-2339","authenticated-orcid":false,"given":"Amir I.","family":"Tukhvatulin","sequence":"first","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1743-0798","authenticated-orcid":false,"given":"Alina S.","family":"Dzharullaeva","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1965-0700","authenticated-orcid":false,"given":"Daria V.","family":"Vasina","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9137-9551","authenticated-orcid":false,"given":"Mikhail V.","family":"Fursov","sequence":"additional","affiliation":[{"name":"The Federal Budgetary Institution of Science \u201cState Research Center for Applied Microbiology and Biotechnology\u201d of the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Territory \u201cKvartal A\u201d, 142279 Obolensk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4110-3941","authenticated-orcid":false,"given":"Fatima M.","family":"Izhaeva","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9422-7238","authenticated-orcid":false,"given":"Denis A.","family":"Kleymenov","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8518-1669","authenticated-orcid":false,"given":"Dmitry N.","family":"Shcherbinin","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1647-5815","authenticated-orcid":false,"given":"Nikita B.","family":"Polyakov","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7389-6157","authenticated-orcid":false,"given":"Andrey I.","family":"Solovyev","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4653-2446","authenticated-orcid":false,"given":"Vladimir G.","family":"Zhukhovitsky","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"},{"name":"The Federal State Budgetary Educational Institution of Further Professional Education \u201cRussian Medical Academy of Continuous Professional Education\u201d of the Ministry of Healthcare of the Russian Federation, 125993 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3993-6909","authenticated-orcid":false,"given":"Alla S.","family":"Zhitkevich","sequence":"additional","affiliation":[{"name":"Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), 108819 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4551-7535","authenticated-orcid":false,"given":"Ilya V.","family":"Gordeychuk","sequence":"additional","affiliation":[{"name":"Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), 108819 Moscow, Russia"},{"name":"Department of Organization and Technology of Immunobiological Drugs, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Litvinova","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-6151","authenticated-orcid":false,"given":"Victor A.","family":"Manuylov","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasiliy D.","family":"Potapov","sequence":"additional","affiliation":[{"name":"The Federal Budgetary Institution of Science \u201cState Research Center for Applied Microbiology and Biotechnology\u201d of the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Territory \u201cKvartal A\u201d, 142279 Obolensk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Artem P.","family":"Tkachuk","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"},{"name":"Federal State Budgetary Institution \u201cNational Medical Research Center for Phthisiopulmonology and Infectious Diseases\u201d of the Ministry of Health of the Russian Federation, 127473 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9397-3762","authenticated-orcid":false,"given":"Vladimir A.","family":"Gushchin","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"},{"name":"Department of Medical Genetics and Postgenomic Technologies, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Department of Virology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4035-6581","authenticated-orcid":false,"given":"Denis Y.","family":"Logunov","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1769-5059","authenticated-orcid":false,"given":"Alexander L.","family":"Gintsburg","sequence":"additional","affiliation":[{"name":"Federal State Budget Institution \u201cNational Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya\u201d of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia"},{"name":"Department of Infectology and Virology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024). 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