{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:54:44Z","timestamp":1772931284665,"version":"3.50.1"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2001,2,1]],"date-time":"2001-02-01T00:00:00Z","timestamp":980985600000},"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":[[2001,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            BCG, the attenuated strain of\n            <jats:italic>Mycobacterium bovis<\/jats:italic>\n            , has been widely used as a vaccine against tuberculosis and is thus an important candidate as a live carrier for multiple antigens. With the aim of developing a recombinant BCG (rBCG) vaccine against diphtheria, pertussis, and tetanus (DPT), we analyzed the potential of CRM\n            <jats:sub>197<\/jats:sub>\n            , a mutated nontoxic derivative of diphtheria toxin, as the recombinant antigen for a BCG-based vaccine against diphtheria. Expression of CRM\n            <jats:sub>197<\/jats:sub>\n            in rBCG was achieved using\n            <jats:italic>Escherichia coli<\/jats:italic>\n            -mycobacterium shuttle vectors under the control of\n            <jats:italic>p<\/jats:italic>\n            BlaF*, an upregulated \u03b2-lactamase promoter from\n            <jats:italic>Mycobacterium fortuitum<\/jats:italic>\n            . Immunization of mice with rBCG-CRM\n            <jats:sub>197<\/jats:sub>\n            elicited an anti-diphtheria toxoid antibody response, but the sera of immunized mice were not able to neutralize diphtheria toxin (DTx) activity. On the other hand, a subimmunizing dose of the conventional diphtheria-tetanus vaccine, administered in order to mimic an infection, showed that rBCG-CRM\n            <jats:sub>197<\/jats:sub>\n            was able to prime the induction of a humoral response within shorter periods. Interestingly, the antibodies produced showed neutralizing activity only when the vaccines had been given as a mixture in combination with rBCG expressing tetanus toxin fragment C (FC), suggesting an adjuvant effect of rBCG-FC on the immune response induced by rBCG-CRM\n            <jats:sub>197<\/jats:sub>\n            . Isotype analysis of the anti-diphtheria toxoid antibodies induced by the combined vaccines, but not rBCG-CRM\n            <jats:sub>197<\/jats:sub>\n            alone, showed an immunoglobulin G1-dominant profile, as did the conventional vaccine. Our results show that rBCG expressing CRM\n            <jats:sub>197<\/jats:sub>\n            can elicit a neutralizing humoral response and encourage further studies on the development of a DPT vaccine with rBCG.\n          <\/jats:p>","DOI":"10.1128\/iai.69.2.869-874.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:01:19Z","timestamp":1027764079000},"page":"869-874","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["Induction of Neutralizing Antibodies against Diphtheria Toxin by Priming with Recombinant\n            <i>Mycobacterium bovis<\/i>\n            BCG Expressing CRM\n            <sub>197<\/sub>\n            , a Mutant Diphtheria Toxin"],"prefix":"10.1128","volume":"69","author":[{"given":"Eliane N.","family":"Miyaji","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Centro de Biotecnologia1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rogerio P.","family":"Mazzantini","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Centro de Biotecnologia1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waldely O.","family":"Dias","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Centro de Biotecnologia1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana L. T. O.","family":"Nascimento","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Centro de Biotecnologia1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rugimar","family":"Marcovistz","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Servic\u0327o de Controle de Qualidade,2 Instituto Butantan, Sa\u0303o Paulo, Brazil;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise S.","family":"Matos","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Servic\u0327o de Controle de Qualidade,2 Instituto Butantan, Sa\u0303o Paulo, Brazil;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaias","family":"Raw","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Centro de Biotecnologia1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Winter","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Laboratoire du BCG3 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"Gicquel","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Laboratoire du BCG3 and"},{"name":"<!--label omitted: 4-->Unite\u0301 de Gene\u0301tique Mycobacte\u0301rienne,4 Institut Pasteur, Paris, France; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rino","family":"Rappuoli","sequence":"additional","affiliation":[{"name":"<!--label omitted: 5-->IRIS, Chiron SpA, Siena, Italy5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana C. C.","family":"Leite","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Centro de Biotecnologia1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-141-7-1585"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.10.5100-5105.1999"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.169.11.5140-5151.1987"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00341a027"},{"key":"e_1_3_2_6_2","unstructured":"Cassatt\nD. R.\nde la Cruz\nV. F.\nBurlein\nJ. E.\nKoenig\nS.\nStover\nC. K.\nProtection of mice against tetanus challenge using an experimental tetanus vaccine based on recombinant BCG\nVaccines '93.\nGinsberg\nH. S.\nBrown\nF.\nChannock\nR. M.\nLerner\nR. 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