{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T07:38:32Z","timestamp":1697614712250},"reference-count":42,"publisher":"American Society for Microbiology","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The low protection by the bacillus Calmette-Gu\u00e9rin (BCG) vaccine and existence of drug-resistant strains require better anti-<jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>vaccines with a broad, long-lasting, antigen-specific response. Using bioinformatics tools, we identified five 19- to 40-mer signal peptide (SP) domain vaccine candidates (VCs) derived from<jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>antigens. All VCs were predicted to have promiscuous binding to major histocompatibility complex (MHC) class I and II alleles in large geographic territories worldwide. Peripheral mononuclear cells (PBMC) from healthy na\u00efve donors and tuberculosis patients exhibited strong proliferation that correlated positively with Th1 cytokine secretion only in healthy na\u00efve donors. Proliferation to SP VCs was superior to that to antigen-matched control peptides with similar length and various MHC class I and II binding properties. T-cell lines induced to SP VCs from healthy na\u00efve donors had increased CD44<jats:sup>high<\/jats:sup>\/CD62L<jats:sup>+<\/jats:sup>activation\/effector memory markers and gamma interferon (IFN-\u03b3), but not interleukin-4 (IL-4), production in both CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T-cell subpopulations. T-cell lines from healthy na\u00efve donors and tuberculosis patients also manifested strong, dose-dependent, antigen-specific cytotoxicity against autologous VC-loaded or<jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>-infected macrophages. Lysis of<jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>-infected targets was accompanied by high IFN-\u03b3 secretion. Various combinations of these five VCs manifested synergic proliferation of PBMC from selected healthy na\u00efve donors. Immunogenicity of the best three combinations, termed Mix1, Mix2, and Mix3 and consisting of 2 to 5 of the VCs, was then evaluated in mice. Each mixture manifested strong cytotoxicity against<jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>-infected macrophages, while Mix3 also manifested a VC-specific humoral immune response. Based on these results, we plan to evaluate the protection properties of these combinations as an improved tuberculosis subunit vaccine.<\/jats:p>","DOI":"10.1128\/cvi.00586-12","type":"journal-article","created":{"date-parts":[[2013,1,3]],"date-time":"2013-01-03T07:18:22Z","timestamp":1357197502000},"page":"328-340","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of Novel Multiantigenic Vaccine Candidates with Pan-HLA Coverage against Mycobacterium tuberculosis"],"prefix":"10.1128","volume":"20","author":[{"given":"Riva","family":"Kovjazin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Shitrit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Preiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilanit","family":"Haim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lev","family":"Triezer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Fuks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdel Rahman","family":"Nader","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meir","family":"Raz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ritta","family":"Bardenstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galit","family":"Horn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nechama I.","family":"Smorodinsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lior","family":"Carmon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2013,1,2]]},"reference":[{"key":"key20180919073643_B1","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1001\/archinte.163.9.1009","article-title":"The growing burden of tuberculosis: global trends and interactions with the HIV epidemic","volume":"163","author":"Corbett","year":"2003","journal-title":"Arch. 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