{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T14:38:18Z","timestamp":1759847898292},"reference-count":51,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"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":[[2009,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The bipartite anthrax lethal toxin (LeTx) consisting of protective antigen (PA) and lethal factor (LF) is a major virulence factor contributing to death from systemic<jats:italic>Bacillus anthracis<\/jats:italic>infection. The current vaccine elicits antibodies directed primarily to PA; however, in experimental settings serologic responses to LF can neutralize LeTx and contribute to protection against infection. The goals of the present study were to identify sequential B-cell epitopes of LF and to determine the capacity of these determinants to bind neutralizing antibodies. Sera of recombinant LF-immunized A\/J mice exhibited high titers of immunoglobulin G anti-LF reactivity that neutralized LeTx in vitro 78 days after the final booster immunization and protected the mice from in vivo challenge with 3 50% lethal doses of LeTx. These sera bound multiple discontinuous epitopes, and there were major clusters of reactivity on native LF. Strikingly, all three neutralizing, LF-specific monoclonal antibodies tested bound specific peptide sequences that coincided with sequential epitopes identified in polyclonal antisera from recombinant LF-immunized mice. This study confirms that LF induces high-titer protective antibodies in vitro and in vivo. Moreover, the binding of short LF peptides by LF-specific neutralizing monoclonal antibodies suggests that generation of protective antibodies by peptide vaccination may be feasible for this antigen. This study paves the way for a more effective anthrax vaccine by identifying discontinuous peptide epitopes of LF.<\/jats:p>","DOI":"10.1128\/iai.00788-08","type":"journal-article","created":{"date-parts":[[2008,11,4]],"date-time":"2008-11-04T01:58:59Z","timestamp":1225763939000},"page":"162-169","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Sequential B-Cell Epitopes of<i>Bacillus anthracis<\/i>Lethal Factor Bind Lethal Toxin-Neutralizing Antibodies"],"prefix":"10.1128","volume":"77","author":[{"given":"Melissa L.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104"},{"name":"Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherry R.","family":"Crowe","sequence":"additional","affiliation":[{"name":"Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sridevi","family":"Kurella","sequence":"additional","affiliation":[{"name":"Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Teryzan","sequence":"additional","affiliation":[{"name":"Crystallography Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Cao","sequence":"additional","affiliation":[{"name":"Laboratory of Antibody Technology, Van Andel Research Institute, Grand Rapids, Michigan 49503"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimmy D.","family":"Ballard","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith A.","family":"James","sequence":"additional","affiliation":[{"name":"Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Darise","family":"Farris","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104"},{"name":"Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00261-07"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0010019"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-8244(03)00085-3"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-765X.2005.01786.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.1999.00899.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2000.00052.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/n35101999"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.11.6313-6317.2004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-140-11-2951"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.19.111301.140655"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.12.7557"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909093411107"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5364.734"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00452-7"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.4049\/jimmunol.162.5.3079","volume":"162","year":"1999","unstructured":"Farris, A. D., L. Brown, P. Reynolds, J. B. Harley, J. A. James, R. H. Scofield, J. McCluskey, and T. P. Gordon. 1999. Induction of autoimmunity by multivalent immunodominant and subdominant T cell determinants of La (SS-B). J. Immunol.162:3079-3087.","journal-title":"J. Immunol."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2004.10.007"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.22.2104"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63697-8"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405557101"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.08.015"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.8.4884-4890.2001"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.2.544-550.2002"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109997200"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00526-0"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.10.6547-6551.2005"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.58.6.1606-1613.1990"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1167"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21682"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32036-7"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052160199"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.6.2111-2116.2001"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/n35101998"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01528-06"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.4.1369-1372.1995"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/am.11.4.330-334.1963"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00708.x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0431098100"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-006-6312-3"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.4.1853-1859.1999"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00529-07"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(98)00042-5"},{"key":"e_1_3_2_44_2","first-page":"293","volume":"177","year":"1988","unstructured":"Turnbull, P. C., S. H. Leppla, M. G. Broster, C. P. Quinn, and J. Melling. 1988. Antibodies to anthrax toxin in humans and guinea pigs and their relevance to protective immunity. Med. Microbiol. Immunol.177:293-303.","journal-title":"Med. Microbiol. Immunol."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3520739"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9040"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2005.00539.x"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-9433-4-4"},{"key":"e_1_3_2_49_2","first-page":"33","volume":"17","year":"2003","unstructured":"Woodrow, P. 2003. Anthrax: forms, symptoms and treatment. Nurs. Stand.17:33-37.","journal-title":"Nurs. Stand."},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00402-07"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.08.056"},{"key":"e_1_3_2_52_2","first-page":"129","volume":"12","year":"2003","unstructured":"Zhao, P., X. Liang, J. Kalbfleisch, H. M. Koo, and B. Cao. 2003. Neutralizing monoclonal antibody against anthrax lethal factor inhibits intoxication in a mouse model. Hum. Antibodies12:129-135.","journal-title":"Hum. Antibodies"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00788-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00788-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:33:25Z","timestamp":1684618405000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00788-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,1]]}},"alternative-id":["10.1128\/IAI.00788-08"],"URL":"https:\/\/doi.org\/10.1128\/iai.00788-08","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,1]]},"assertion":[{"value":"2008-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-10-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}