{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:06:34Z","timestamp":1778717194845,"version":"3.51.4"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2009,11,1]],"date-time":"2009-11-01T00:00:00Z","timestamp":1257033600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Brucella<\/jats:italic>spp. are gram-negative bacteria that cause the most frequent zoonotic disease worldwide, with more than 500,000 human infections yearly; however, no human vaccine is currently available. As with other intracellular organisms, cytotoxic mechanisms against infected cells are thought to have an important role in controlling infection and mediating long-term immunity. Live attenuated strains developed for use in animals elicit protection but retain unacceptable levels of virulence. Thus, the optimal design for a brucellosis vaccine requires a nonliving vaccine that confers effective immunity. Historically, inactivation methods such as chemical or heat treatment successfully impair<jats:italic>Brucella<\/jats:italic>reproductive capacity; nevertheless, metabolically inactive vaccines (subunit or killed) present very limited efficacy. Hence, we hypothesized that bacterial metabolism plays a major role in creating the proper antigenic and adjuvant properties required for efficient triggering of protective responses. Here, we demonstrate that inactivation of<jats:italic>Brucella melitensis<\/jats:italic>by gamma-irradiation inhibited its replication capability and yet retained live-<jats:italic>Brucella<\/jats:italic>protective features. Irradiated<jats:italic>Brucella<\/jats:italic>possessed metabolic and transcriptional activity, persisted in macrophages, generated antigen-specific cytotoxic T cells, and protected mice against virulent bacterial challenge, without signs of residual virulence. In conclusion, pathogen metabolic activity has a positive role in shaping protective responses, and the generation of inactivated and yet metabolically active microbes is a promising strategy for safely vaccinating against intracellular organisms such as<jats:italic>B. melitensis<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/iai.00231-09","type":"journal-article","created":{"date-parts":[[2009,8,25]],"date-time":"2009-08-25T01:11:00Z","timestamp":1251162660000},"page":"5181-5189","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Nondividing but Metabolically Active Gamma-Irradiated<i>Brucella melitensis<\/i>Is Protective against Virulent<i>B. melitensis<\/i>Challenge in Mice"],"prefix":"10.1128","volume":"77","author":[{"given":"D. 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