{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:26:10Z","timestamp":1792740370839,"version":"4.5.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"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":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The development of new protein subunit vaccines has stimulated the search for improved adjuvants to replace traditional aluminum-containing products. We investigated the adjuvant effects of a synthetic Toll-like receptor 4 (TLR4) agonist on vaccine efficacy in an experimental model of toxic shock syndrome. The TLR4 agonist E6020 has a simplified structure consisting of a hexa-acylated acyclic backbone. The vaccine examined is a recombinantly attenuated form of staphylococcal enterotoxin B (STEBVax). Using cells stably transfected with TLRs, E6020 transduced signals only through TLR4, suggesting monospecificity, while\n            <jats:italic>Escherichia coli<\/jats:italic>\n            055:B5 lipopolysaccharide activated both the TLR2\/6 heterodimer and TLR4. Coadministration of E6020 with STEBVax, by the intramuscular or intranasal route, induced significant levels of immunoglobulin G (IgG) in BALB\/c mice. Further, increased IgG production resulted from the combination of E6020 with aluminum hydroxide adjuvant (AH). The antibody response to the vaccine coadministered with E6020 was a mixed Th1\/Th2 response, as opposed to the Th2-biased response obtained with AH. Mice vaccinated with STEBVax coadministered with AH, TLR4 agonists, or a combination of both adjuvants were protected from toxic shock. Our data demonstrate the effectiveness of the synthetic TLR4 agonist E6020 as an alternative adjuvant for protein subunit vaccines that may also be used in combination with traditional aluminum-containing adjuvants.\n          <\/jats:p>","DOI":"10.1128\/cvi.00153-07","type":"journal-article","created":{"date-parts":[[2007,8,23]],"date-time":"2007-08-23T00:49:47Z","timestamp":1187830187000},"page":"1499-1504","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Synthetic Toll-Like Receptor 4 Agonist Enhances Vaccine Efficacy in an Experimental Model of Toxic Shock Syndrome"],"prefix":"10.1128","volume":"14","author":[{"given":"Garry L.","family":"Morefield","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702"},{"name":"Eisai Research Institute, Andover, Massachusetts 01887"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn D.","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702"},{"name":"Eisai Research Institute, Andover, Massachusetts 01887"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally T.","family":"Ishizaka","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702"},{"name":"Eisai Research Institute, Andover, Massachusetts 01887"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teri L.","family":"Kissner","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702"},{"name":"Eisai Research Institute, Andover, Massachusetts 01887"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702"},{"name":"Eisai Research Institute, Andover, Massachusetts 01887"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S1521-6616(03)00066-4","volume":"108","year":"2003","unstructured":"Boles, J. W., M. L. Pitt, R. D. LeClaire, P. H. Gibbs, E. Torres, B. Dyas, R. G. Ulrich, and S. Bavari. 2003. Generation of protective immunity by inactivated recombinant staphylococcal enterotoxin B vaccine in nonhuman primates and identification of correlates of immunity. Clin. Immunol.108:51-59.","journal-title":"Clin. Immunol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.16.10689"},{"key":"e_1_3_2_4_2","first-page":"113","volume":"87","year":"1996","unstructured":"Corbel, M. J. 1996. Reasons for instability of bacterial vaccines. Dev. Biol. Stand.87:113-124.","journal-title":"Dev. Biol. Stand."},{"key":"e_1_3_2_5_2","first-page":"291","volume":"124","year":"1969","unstructured":"Fekety, F. R., Jr. 1969. Skin window studies of the effect of endotoxin upon the acute inflammatory response. Johns Hopkins Med. J.124:291-295.","journal-title":"Johns Hopkins Med. J."},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S1357-4310(99)01657-3","volume":"6","year":"2000","unstructured":"Fraser, J., V. Arcus, P. Kong, E. Baker, and T. Proft. 2000. Superantigens\u2014powerful modifiers of the immune system. Mol. Med. Today6:125-132.","journal-title":"Mol. Med. Today"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0264-410X(01)00322-X","volume":"20","year":"2001","unstructured":"Ghosh, A., W. W. Zhang, and G. Matlashewski. 2001. Immunization with A2 protein results in a mixed Th1\/Th2 and a humoral response which protects mice against Leishmania donovani infections. Vaccine20:59-66.","journal-title":"Vaccine"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0898-6568(00)00149-2","volume":"13","year":"2001","unstructured":"Guha, M., and N. Mackman. 2001. LPS induction of gene expression in human monocytes. Cell. Signal.13:85-94.","journal-title":"Cell. Signal."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1124\/jpet.300.2.655","volume":"300","year":"2002","unstructured":"Hawkins, L. D., S. T. Ishizaka, P. McGuinness, H. Zhang, W. Gavin, B. DeCosta, Z. Meng, H. Yang, M. Mullarkey, D. W. Young, H. Yang, D. P. Rossignol, A. Nault, J. Rose, M. Przetak, J. C. Chow, and F. Gusovsky. 2002. A novel class of endotoxin receptor agonists with simplified structure, toll-like receptor 4-dependent immunostimulatory action, and adjuvant activity. J. Pharmacol. Exp. Ther.300:655-661.","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"618","DOI":"10.4049\/jimmunol.165.2.618","volume":"165","year":"2000","unstructured":"Hirschfeld, M., Y. Ma, J. H. Weis, S. N. Vogel, and J. J. Weis. 2000. Repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J. Immunol.165:618-622.","journal-title":"J. Immunol."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1112"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/j.vaccine.2005.09.048","volume":"24","year":"2006","unstructured":"Jiang, D., G. L. Morefield, H. HogenEsch, and S. L. Hem. 2006. Relationship of adsorption mechanism of antigens by aluminum-containing adjuvants to in vitro elution in interstitial fluid. Vaccine24:1665-1669.","journal-title":"Vaccine"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2174\/1566524033479726","volume":"3","year":"2003","unstructured":"Kaisho, T., and S. Akira. 2003. Regulation of dendritic cell function through Toll-like receptors. Curr. Mol. Med.3:373-385.","journal-title":"Curr. Mol. Med."},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1046\/j.1365-3083.2002.01049.x","volume":"55","year":"2002","unstructured":"Lagranderie, M., A. M. Balazuc, M. Abolhassani, P. Chavarot, M. A. Nahori, F. Thouron, G. Milon, and G. Marchal. 2002. Development of mixed Th1\/Th2 type immune response and protection against Mycobacterium tuberculosis after rectal or subcutaneous immunization of newborn and adult mice with Mycobacterium bovis BCG. Scand. J. Immunol.55:293-303.","journal-title":"Scand. J. Immunol."},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/S0952-7915(97)80152-5","volume":"9","year":"1997","unstructured":"Medzhitov, R., and C. A. Janeway, Jr. 1997. Innate immunity: impact on the adaptive immune response. Curr. Opin. Immunol.9:4-9.","journal-title":"Curr. Opin. Immunol."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/S0966-842X(00)01845-X","volume":"8","year":"2000","unstructured":"Medzhitov, R., and C. Janeway, Jr. 2000. The Toll receptor family and microbial recognition. Trends Microbiol.8:452-456.","journal-title":"Trends Microbiol."},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"5998","DOI":"10.4049\/jimmunol.164.11.5998","volume":"164","year":"2000","unstructured":"Muzio, M., D. Bosisio, N. Polentarutti, G. D'Amico, A. Stoppacciaro, R. Mancinelli, C. van't Veer, G. Penton-Rol, L. P. Ruco, P. Allavena, and A. Mantovani. 2000. Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J. Immunol.164:5998-6004.","journal-title":"J. Immunol."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.2.692-701.2002"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb4100057"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1126\/science.282.5396.2085","volume":"282","year":"1998","unstructured":"Poltorak, A., X. He, I. Smirnova, M. Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, M. Freudenberg, P. Ricciardi-Castagnoli, B. Layton, and B. Beutler. 1998. Defective LPS signaling in C3H\/HeJ and C57BL\/10ScCr mice: mutations in Tlr4 gene. Science282:2085-2088.","journal-title":"Science"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/S0264-410X(02)00737-5","volume":"21","year":"2003","unstructured":"Przetak, M., J. Chow, H. Cheng, J. Rose, L. D. Hawkins, and S. T. Ishizaka. 2003. Novel synthetic LPS receptor agonists boost systemic and mucosal antibody responses in mice. Vaccine21:961-970.","journal-title":"Vaccine"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0966-842X(00)89011-3","volume":"3","year":"1995","unstructured":"Ulrich, R. G., S. Bavari, and M. A. Olson. 1995. Bacterial superantigens in human disease: structure, function and diversity. Trends Microbiol.3:463-468.","journal-title":"Trends Microbiol."},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/nsb0795-554","volume":"2","year":"1995","unstructured":"Ulrich, R. G., S. Bavari, and M. A. Olson. 1995. Staphylococcal enterotoxins A and B share a common structural motif for binding class II major histocompatibility complex molecules. Nat. Struct. Biol.2:554-560.","journal-title":"Nat. Struct. Biol."},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1016\/S0264-410X(98)00176-5","volume":"16","year":"1998","unstructured":"Ulrich, R. G., S. Bavari, and M. A. Olson. 1998. Development of engineered vaccines effective against structurally related bacterial superantigens. Vaccine16:1857-1864.","journal-title":"Vaccine"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1002\/eji.200324037","volume":"33","year":"2003","unstructured":"Underhill, D. M. 2003. Toll-like receptors: networking for success. Eur. J. Immunol.33:1767-1775.","journal-title":"Eur. J. Immunol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4049\/jimmunol.166.1.249","volume":"166","year":"2001","unstructured":"Visintin, A., A. Mazzoni, J. H. Spitzer, D. H. Wyllie, S. K. Dower, and D. M. Segal. 2001. Regulation of Toll-like receptors in human monocytes and dendritic cells. J. Immunol.166:249-255.","journal-title":"J. Immunol."}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00153-07","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00153-07","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:37:36Z","timestamp":1627591056000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00153-07"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2007,11]]}},"alternative-id":["10.1128\/CVI.00153-07"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00153-07","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,11]]},"assertion":[{"value":"2007-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-08-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}