{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T13:06:43Z","timestamp":1759410403232},"reference-count":45,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"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":[[2008,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Francisella tularensis<\/jats:italic>causes severe pneumonia that can be fatal if it is left untreated. Due to its potential use as a biological weapon, research is being conducted to develop an effective vaccine and to select and study adjuvant molecules able to generate a better and long-lasting protective effect. PorB, a porin from<jats:italic>Neisseria meningitidis<\/jats:italic>, is a well-established Toll-like receptor 2 ligand and has been shown to be a promising vaccine adjuvant candidate due to its ability to enhance the T-cell costimulatory activity of antigen-presenting cells both in vitro and in vivo. BALB\/c mice were immunized with lipopolysaccharide (LPS) isolated from the<jats:italic>F. tularensis<\/jats:italic>subsp.<jats:italic>holarctica<\/jats:italic>live vaccine strain (LVS), with or without PorB from<jats:italic>N. meningitidis<\/jats:italic>, and the antibody levels induced during the vaccination regimen and the level of protection against intranasal challenge with LVS were determined. Antigen administered alone induced a specific<jats:italic>F. tularensis<\/jats:italic>LPS immunoglobulin M (IgM) response that was not maintained over the weeks and that conferred protection to only 25% of the mice. In contrast,<jats:italic>F. tularensis<\/jats:italic>LPS given in combination with neisserial PorB induced consistent levels of specific IgM throughout the immunization and increased the proportion of surviving mice to 70%. Postchallenge cytokine analysis showed that interleukin-6 (IL-6), monocyte chemoattractant protein 1, and gamma interferon were markers of mortality and that IL-1\u03b2 was a correlate of survival, independent of the presence of PorB as an adjuvant. These data indicate that neisserial PorB might be an optimal candidate adjuvant for improving the protective effect of<jats:italic>F. tularensis<\/jats:italic>LPS and other subunit vaccines against tularemia, but there is still a need to test its efficacy against virulent type A and type B<jats:italic>F. tularensis<\/jats:italic>strains.<\/jats:p>","DOI":"10.1128\/cvi.00125-08","type":"journal-article","created":{"date-parts":[[2008,7,10]],"date-time":"2008-07-10T00:45:50Z","timestamp":1215650750000},"page":"1322-1329","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["<i>Neisseria meningitidis<\/i>PorB, a Toll-Like Receptor 2 Ligand, Improves the Capacity of<i>Francisella tularensis<\/i>Lipopolysaccharide To Protect Mice against Experimental Tularemia"],"prefix":"10.1128","volume":"15","author":[{"given":"Damiana","family":"Chiavolini","sequence":"first","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Weir","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee M.","family":"Wetzler","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.6.2041-2046.1996"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01606-06"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1189\/jlb.1104637","volume":"77","year":"2005","unstructured":"Bolger, C. E., C. A. Forestal, J. K. Italo, J. L. Benach, and M. B. Furie. 2005. The live vaccine strain of Francisella tularensis replicates in human and murine macrophages but induces only the human cells to secrete proinflammatory cytokines. J. Leukoc. Biol.77:893-897.","journal-title":"J. Leukoc. Biol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.4049\/jimmunol.179.5.3222","volume":"179","year":"2007","unstructured":"Burke, J. M., L. M. Ganley-Leal, K. Khatri, and L. M. Wetzler. 2007. Neisseria meningitidis PorB, a TLR2 ligand, induces an antigen-specific eosinophil recall response: potential adjuvant for helminth vaccines? J. Immunol.179:3222-3230.","journal-title":"J. Immunol."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00862-07"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"6888","DOI":"10.4049\/jimmunol.176.11.6888","volume":"176","year":"2006","unstructured":"Cole, L. E., K. L. Elkins, S. M. Michalek, N. Qureshi, L. J. Eaton, P. Rallabhandi, N. Cuesta, and S. N. Vogel. 2006. Immunologic consequences of Francisella tularensis live vaccine strain infection: role of the innate immune response in infection and immunity. J. Immunol.176:6888-6899.","journal-title":"J. Immunol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01868-06"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"3465","DOI":"10.1016\/S0264-410X(02)00345-6","volume":"20","year":"2002","unstructured":"Conlan, J. W., H. Shen, A. Webb, and M. B. Perry. 2002. Mice vaccinated with the O-antigen of Francisella tularensis LVS lipopolysaccharide conjugated to bovine serum albumin develop varying degrees of protective immunity against systemic or aerosol challenge with virulent type A and type B strains of the pathogen. Vaccine20:3465-3470.","journal-title":"Vaccine"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0882-4010(02)00194-8","volume":"34","year":"2003","unstructured":"Conlan, J. W., E. Vinogradov, M. A. Monteiro, and M. B. Perry. 2003. Mice intradermally-inoculated with the intact lipopolysaccharide, but not the lipid A or O-chain, from Francisella tularensis LVS rapidly acquire varying degrees of enhanced resistance against systemic or aerogenic challenge with virulent strains of the pathogen. Microb. Pathog.34:39-45.","journal-title":"Microb. Pathog."},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/S0264-410X(96)00183-1","volume":"15","year":"1997","unstructured":"Cox, J. C., and A. R. Coulter. 1997. Adjuvants\u2014a classification and review of their modes of action. Vaccine15:248-256.","journal-title":"Vaccine"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.4.1988-1996.2000"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.4.2306-2311.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.4049\/jimmunol.87.4.415","volume":"87","year":"1961","unstructured":"Eigelsbach, H. T., and C. M. Downs. 1961. Prophylactic effectiveness of live and killed tularemia vaccines. Part I. Production of vaccine and evaluation of in the white mouse and guinea pig. J. Immunol.87:415-425.","journal-title":"J. Immunol."},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.micpath.2007.08.009","volume":"44","year":"2008","unstructured":"Eyles, J. E., M. G. Hartley, T. R. Laws, P. C. F. Oyston, K. F. Griffin, and R. W. Titball. 2008. Protection afforded against aerosol challenge by systemic immunisation with inactivated Francisella tularensis live vaccine strain (LVS). Microb. Pathog.44:164-168.","journal-title":"Microb. Pathog."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/bmb\/ldh021","volume":"70","year":"2004","unstructured":"Finn, A. 2004. Bacterial polysaccharide-protein conjugate vaccines. Br. Med. Bull.70:1-14.","journal-title":"Br. Med. Bull."},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.2105\/AJPH.32.10.1131","volume":"32","year":"1942","unstructured":"Foshay, L., W. H. Hesselbrock, H. J. Wittenberg, and A. H. Rodenberg. 1942. Vaccine prophylaxis against tularemia in man. Am. J. Public Health32:1131-1145.","journal-title":"Am. J. Public Health"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/0264-410X(95)00062-6","volume":"13","year":"1995","unstructured":"Fulop, M., R. Manchee, and R. W. Titball. 1995. Role of lipopolysaccharide and a major outer membrane protein from Francisella tularensis in the induction of immunity against tularemia. Vaccine13:1220-1225.","journal-title":"Vaccine"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1073\/pnas.0504271103","volume":"103","year":"2006","unstructured":"Gavrilin, M. A., I. J. Bouskl, N. L. Knatz, M. D. Duncan, M. W. Hall, J. S. Gunn, and M. D. Wewers. 2006. Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release. Proc. Natl. Acad. Sci. USA103:141-146.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0264-410X(95)93311-V","volume":"13","year":"1995","unstructured":"Golovliov, I., M. Ericsson, L. Akerblom, G. Sandstrom, A. Tarnvik, and A. Sjostedt. 1995. Adjuvanticity of ISCOMs incorporating a T cell-reactive lipoprotein of the facultative intracellular pathogen Francisella tularensis. Vaccine13:261-267.","journal-title":"Vaccine"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1574-695X.2007.00219.x","volume":"49","year":"2007","unstructured":"Griffin, K. F., P. C. F. Oyston, and R. W. Titball. 2007. Francisella tularensis vaccines. FEMS Immunol. Med. Microbiol.49:315-323.","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"e_1_3_2_22_2","first-page":"505","volume":"5","year":"2007","unstructured":"Guy, B. 2007. The perfect mix: recent progress in adjuvant research. Nat. Rev. Microbiol.5:505-517.","journal-title":"Nat. Rev. Microbiol."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.7.4109-4113.2004"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/br.30.3.532-538.1966"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.5.2809-2816.2006"},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.4049\/jimmunol.172.4.2431","volume":"172","year":"2004","unstructured":"Latz, E., J. Franko, D. T. Golenbock, and J. R. Schreiber. 2004. Haemophilus influenzae type b-outer membrane protein complex glycoconjugate vaccine induces cytokine production by engaging human Toll-like receptor 2 (TLR2) and requires the presence of TLR2 for optimal immunogenicity. J. Immunol.172:2431-2438.","journal-title":"J. Immunol."},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1086\/314966","volume":"180","year":"1999","unstructured":"Mackinnon, F. G., Y. Ho, M. S. Blake, F. Michon, A. Chandraker, M. H. Sayegh, and L. M. Wetzler. 1999. The role of B\/T costimulatory signals in the immunopotentiating activity of neisserial porin. J. Infect. Dis.180:755-761.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_28_2","first-page":"pe48","volume":"402","year":"2007","unstructured":"MacLeod, H., and L. M. Wetzler. 2007. T cell activation by TLRs: a role for TLRs in the adaptive immune response. Sci. STKE402:pe48.","journal-title":"Sci. STKE"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02030-05"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.5.2498-2507.2003"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.4049\/jimmunol.168.4.1533","volume":"168","year":"2002","unstructured":"Massari, P., P. Henneke, Y. Ho, E. Latz, D. T. Golenbock, and L. M. Wetzler. 2002. Cutting edge: immune stimulation by neisserial porins is Toll-like receptor 2 and MyD88 dependent. J. Immunol.168:1533-1537.","journal-title":"J. Immunol."},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.pep.2005.04.021","volume":"44","year":"2005","unstructured":"Massari, P., C. A. King, H. MacLeod, and L. M. Wetzler. 2005. Improved purification of native meningococcal porin PorB and studies on its structure\/function. Protein Expr. Purif.44:136-146.","journal-title":"Protein Expr. Purif."},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.4049\/jimmunol.176.4.2373","volume":"176","year":"2006","unstructured":"Massari, P., A. Visintin, J. Gunawardana, K. A. Halmen, C. A. King, D. T. Golenbock, and L. M. Wetzler. 2006. Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling. J. Immunol.176:2373-2380.","journal-title":"J. Immunol."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/br.25.3.262-267.1961"},{"key":"e_1_3_2_35_2","first-page":"25680","volume":"276","year":"2001","unstructured":"Michelsen, K. S., A. Aicher, and M. Mohaupt. 2001. The role of Toll-like receptors (TLRs) in bacteria-induced maturation of murine dendritic cells (DCs). Peptidoglycan and lipoteichoic acid are inducers of DC maturation and require TLR2. J. Immunol.276:25680-25686.","journal-title":"J. Immunol."},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S1389-0344(01)00101-0","volume":"18","year":"2001","unstructured":"O'Hagan, D. T., M. L. MacKichan, and M. Singh. 2001. Recent developments in adjuvants for vaccines against infectious diseases. Biomol. Eng.18:69-85.","journal-title":"Biomol. Eng."},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.6.2075-2082.1991"},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.0105-2896.2004.00144.x","volume":"199","year":"2004","unstructured":"Pulendran, B. 2004. Modulating vaccine responses with dendritic cells and Toll-like receptors. Immunol. Rev.199:227-250.","journal-title":"Immunol. Rev."},{"key":"e_1_3_2_39_2","first-page":"201","volume":"5","year":"1992","unstructured":"Sandstrom, G., A. Sjostedt, T. Johansson, K. Kuoppa, and J. C. Williams. 1992. Immunogenicity and toxicity of lipopolysaccharide from Francisella tularensis LVS. FEMS Microbiol. Immunol.5:201-210.","journal-title":"FEMS Microbiol. Immunol."},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1001\/archinte.1961.03620050055006","volume":"107","year":"1961","unstructured":"Saslaw, S., H. T. Eigelsbach, J. A. Prior, H. E. Wilson, and S. Carhart. 1961. Tularemia vaccine study. Part II. Respiratory challenge. Arch. Intern. Med.107:689-701.","journal-title":"Arch. Intern. Med."},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","first-page":"3545","DOI":"10.4049\/jimmunol.174.6.3545","volume":"174","year":"2005","unstructured":"Singleton, T. E., P. Massari, and L. M. Wetzler. 2005. Neisserial porin-induced dendritic cell activation is MyD88 and TLR2 dependent. J. Immunol.174:3545-3550.","journal-title":"J. Immunol."},{"key":"e_1_3_2_42_2","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1093\/clinids\/11.3.440","volume":"11","year":"1989","unstructured":"Tarnvik, A. 1989. Nature of protective immunity to Francisella tularensis. Rev. Infect. Dis.11:440-451.","journal-title":"Rev. Infect. Dis."},{"key":"e_1_3_2_43_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1574-695X.1996.tb00242.x","volume":"13","year":"1996","unstructured":"Tarnvik, A., M. Ericsson, I. Golovliov, G. Sandstrom, and A. Sjostedt. 1996. Orchestration of the protective immune response to intracellular bacteria: Francisella tularensis as a model organism. FEMS Immunol. Med. Microbiol.13:221-225.","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"e_1_3_2_44_2","doi-asserted-by":"crossref","first-page":"48122","DOI":"10.1074\/jbc.M206941200","volume":"277","year":"2002","unstructured":"Van der Kleij, D., E. Latz, J. F. Brouwers, Y. C. Kruize, M. Schmitz, E. A. Kurt-Jones, T. Espevik, E. C. De Jong, M. L. Kapsenberg, D. T. Golenbock, A. G. Tielens, and M. Yazdanbakhsh. 2002. A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J. Biol. Chem.277:48122-48129.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_45_2","doi-asserted-by":"crossref","first-page":"5263","DOI":"10.1016\/j.vaccine.2005.06.024","volume":"23","year":"2005","unstructured":"Weeratna, R. D., S. R. Makinen, M. J. McCluskie, and H. L. Davis. 2005. TLR agonists as vaccine adjuvants: comparison of CpG ODN and Resiquimod (R-848). Vaccine23:5263-5270.","journal-title":"Vaccine"},{"key":"e_1_3_2_46_2","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1016\/S0264-410X(03)00201-9","volume":"21","year":"2003","unstructured":"Wetzler, L. M. 2003. The role of Toll-like receptors 2 in microbial disease and immunity. Vaccine21(Suppl. 2):S55-S60.","journal-title":"Vaccine"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00125-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00125-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T04:21:09Z","timestamp":1684470069000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00125-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9]]},"references-count":45,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2008,9]]}},"alternative-id":["10.1128\/CVI.00125-08"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00125-08","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9]]},"assertion":[{"value":"2008-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-06-30","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"}}]}}