{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:18:25Z","timestamp":1790104705612,"version":"4.0.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2009,8,1]],"date-time":"2009-08-01T00:00:00Z","timestamp":1249084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The immunostimulatory activity of lipids associated with the mycobacterial cell wall has been recognized for several decades and exploited in a large variety of different adjuvant preparations. Previously, we have shown that a mycobacterial lipid extract from Mycobacterium bovis bacillus Calmette-Gu\u00e9rin delivered in cationic liposomes was a particular efficient Th1-inducing adjuvant formulation effective against tuberculosis. Herein, we have dissected the adjuvant activity of the bacillus Calmette-Gu\u00e9rin lipid extract showing that the majority of the activity was attributable to the apolar lipids and more specifically to a single lipid, monomycoloyl glycerol (MMG), previously also shown to stimulate human dendritic cells. Delivered in cationic liposomes, MMG induced the most prominent Th1-biased immune response that provided significant protection against tuberculosis. Importantly, a simple synthetic analog of MMG, based on a 32 carbon mycolic acid, was found to give rise to comparable high Th1-biased responses with a major representation of polyfunctional CD4 T cells coexpressing IFN-\u03b3, TNF-\u03b1, and IL-2. Furthermore, comparable activity was shown by an even simpler monoacyl glycerol analog, based on octadecanoic acid. The use of these synthetic analogs of MMG represents a promising new strategy for exploiting the immunostimulatory activity and adjuvant potential of components from the mycobacterial cell wall without the associated toxicity issues observed with complex mycobacterial preparations.<\/jats:p>","DOI":"10.4049\/jimmunol.0804091","type":"journal-article","created":{"date-parts":[[2009,7,21]],"date-time":"2009-07-21T00:55:04Z","timestamp":1248137704000},"page":"2294-2302","source":"Crossref","is-referenced-by-count":42,"title":["Novel Generation Mycobacterial Adjuvant Based on Liposome-Encapsulated Monomycoloyl Glycerol from <i>Mycobacterium bovis<\/i> Bacillus Calmette-Gu\u00e9rin"],"prefix":"10.1093","volume":"183","author":[{"given":"Claire A Swetman","family":"Andersen","sequence":"first","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Rosenkrands","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja W","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernille","family":"Nordly","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Lang","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut, Universit\u00e4tsklinikum Erlangen , Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Kirschning","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Immunologie und Hygiene , Munchen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veemal","family":"Bhowruth","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham , Edgbaston, Birmingham,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E","family":"Minnikin","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham , Edgbaston, Birmingham,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurdyal S","family":"Besra","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham , Edgbaston, Birmingham,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Follmann","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Else Marie","family":"Agger","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,8,15]]},"reference":[{"key":"2025032709114050600_R1","volume-title":"The Bacterial Lipids","year":"1966"},{"key":"2025032709114050600_R2","first-page":"95","article-title":"Lipids: complex lipids, their chemistry, biosynthesis and roles. C. Ratledge, and J. L. Stanford, eds.","volume-title":"The Biology of the Mycobacteria","year":"1982"},{"key":"2025032709114050600_R3","first-page":"5235","article-title":"Activation of dendritic cells by liposomes prepared from phosphatidylinositol mannosides from Mycobacterium bovis bacillus Calmette-Gu\u00e9rin and adjuvant activity in vivo.","volume-title":"Infect. Immun.","year":"2004"},{"key":"2025032709114050600_R4","first-page":"5007","article-title":"In vivo activity of released cell wall lipids of Mycobacterium bovis bacillus Calmette-Gu\u00e9rin is due principally to trehalose mycolates.","volume-title":"J. Immunol.","year":"2005"},{"key":"2025032709114050600_R5","first-page":"159","article-title":"Cell wall lipids from Mycobacterium bovis BCG are inflammatory when inoculated within a gel matrix: characterization of a new model of the granulomatous response to mycobacterial components.","volume-title":"Tuberculosis","year":"2005"},{"key":"2025032709114050600_R6","first-page":"5817","article-title":"Cationic liposomes containing mycobacterial lipids: a new powerful Th1 adjuvant system.","volume-title":"Infect. Immun.","year":"2005"},{"key":"2025032709114050600_R7","first-page":"424","article-title":"A simple mycobacterial monomycolated glycerol lipid has immunostimulatory activity.","volume-title":"J. Immunol.","year":"2009"},{"key":"2025032709114050600_R8","first-page":"237","article-title":"Systematic analysis of complex mycobacterial lipids. M. Goodfellow, and D. E. Minnikin, eds.","volume-title":"Chemical Methods in Bacterial Systematics","year":"1985"},{"key":"2025032709114050600_R9","first-page":"2029","article-title":"Adjuvant properties of a simplified C32 monomycoloylglycerol analogue.","volume-title":"Bioorg. Med. Chem. Lett.","year":"2009"},{"key":"2025032709114050600_R10","first-page":"2773","article-title":"Protection of mice with a tuberculosis subunit vaccine based on a fusion protein of antigen 85b and esat-6.","volume-title":"Infect. Immun.","year":"2001"},{"key":"2025032709114050600_R11","first-page":"1258","article-title":"Identification of CT521 as a frequent target of Th1 cells in patients with urogenital Chlamydia trachomatis infection.","volume-title":"J. Infect. Dis.","year":"2006"},{"key":"2025032709114050600_R12","first-page":"897","article-title":"Antigenic profiling of a Chlamydia trachomatis gene-expression library.","volume-title":"J. Infect. 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Cancer","year":"1979"},{"key":"2025032709114050600_R23","first-page":"22","article-title":"Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from M. tuberculosis (trehalose 6,6\u2032-dibehenate)-a novel adjuvant inducing both strong CMI and antibody responses.","volume-title":"Biochim. Biophys. Acta","year":"2005"},{"key":"2025032709114050600_R24","first-page":"758","article-title":"Liposome delivery of C. muridarum MOMP primes a Th1 response that protect against genital Chlamydia infection in a mouse model.","volume-title":"J. Infect. Dis.","year":"2008"},{"key":"2025032709114050600_R25","first-page":"1087","article-title":"Intracellular signalling cascades regulating innate immune responses to mycobacteria: branching out from Toll-like receptors.","volume-title":"Cell. Microbiol.","year":"2007"},{"key":"2025032709114050600_R26","first-page":"1790","article-title":"Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88.","volume-title":"J. Clin. Invest.","year":"2004"},{"key":"2025032709114050600_R27","first-page":"1305","article-title":"Chronic pneumonia despite adaptive immune response to Mycobacterium bovis BCG in MyD88-deficient mice.","volume-title":"Lab. Invest.","year":"2004"},{"key":"2025032709114050600_R28","first-page":"1936","article-title":"Adjuvant-enhanced antibody responses in the absence of Toll-like receptor signaling.","volume-title":"Science","year":"2006"},{"key":"2025032709114050600_R29","first-page":"6303","article-title":"Essential role of the MyD88 pathway, but nonessential roles of TLRs 2, 4, and 9, in the adjuvant effect promoting Th1-mediated autoimmunity.","volume-title":"J. 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