{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:57:23Z","timestamp":1717203443561},"reference-count":42,"publisher":"American Society for Microbiology","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content content-type=\"genus-species\">Mycobacterium bovis<\/jats:named-content>bacillus Calmette-Gu\u00e9rin (BCG) is an attractive target for development as a live vaccine vector delivering transgenic antigens from HIV and other pathogens. Most studies aimed at defining the clearance of BCG have been performed at doses between 10<jats:sup>2<\/jats:sup>and 10<jats:sup>4<\/jats:sup>CFU. Interestingly, however, recombinant BCG (rBCG) administered at doses of &gt;10<jats:sup>6<\/jats:sup>CFU effectively generates antigen-specific T-cell responses and primes for heterologous boost responses. Thus, defining clearance at high doses might aid in the optimization of rBCG as a vector. In this study, we used bioluminescence imaging to examine the kinetics of rBCG transgene expression and clearance in mice immunized with 5 \u00d7 10<jats:sup>7<\/jats:sup>CFU rBCG expressing luciferase. Similar to studies using low-dose rBCG, our results demonstrate that the adaptive immune response is necessary for long-term control of rBCG beginning 9 days after immunizing mice. However, in contrast to these reports, we observed that the majority of mycobacterial antigen was eliminated prior to day 9. By examining knockout and antibody-mediated depletion mouse models, we demonstrate that the rapid clearance of rBCG occurs in the first 24 h and is mediated by Gr-1<jats:sup>+<\/jats:sup>cells. As Gr-1<jats:sup>+<\/jats:sup>granulocytes have been described as having no impact on BCG clearance at low doses, our results reveal an unappreciated role for Gr-1<jats:sup>+<\/jats:sup>neutrophils and inflammatory monocytes in the clearance of high-dose rBCG. This work demonstrates the potential of applying bioluminescence imaging to rBCG in order to gain an understanding of the immune response and increase the efficacy of rBCG as a vaccine vector.<\/jats:p>","DOI":"10.1128\/cvi.00363-14","type":"journal-article","created":{"date-parts":[[2014,6,12]],"date-time":"2014-06-12T07:53:39Z","timestamp":1402559619000},"page":"1120-1127","source":"Crossref","is-referenced-by-count":1,"title":["Role for Gr-1<sup>+<\/sup>Cells in the Control of High-Dose Mycobacterium bovis Recombinant BCG"],"prefix":"10.1128","volume":"21","author":[{"given":"Michael W.","family":"Panas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman L.","family":"Letvin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2014,6,11]]},"reference":[{"key":"key20180919073740_B1","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1111\/all.12099","article-title":"Distant lymph nodes serve as pools of Th1 cells induced by neonatal BCG vaccination for the prevention of asthma in mice","volume":"68","author":"Zhang","year":"2013","journal-title":"Allergy"},{"key":"key20180919073740_B2","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1186\/1471-2172-14-S1-S5","article-title":"Immunogenicity of recombinant Mycobacterium bovis bacille Calmette-Gu\u00e8rin clones expressing T and B cell epitopes of Mycobacterium tuberculosis antigens","volume":"14","author":"Mohamud","year":"2013","journal-title":"BMC Immunol."},{"key":"key20180919073740_B3","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1165\/ajrcmb.22.3.3776","article-title":"Pulmonary immune responses during primary Mycobacterium bovis\u2013Calmette-Guerin bacillus infection in C57Bl\/6 mice","volume":"22","author":"Fulton","year":"2000","journal-title":"Am. 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