{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T23:58:20Z","timestamp":1788393500200,"version":"build-2803163510"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2009,8,1]],"date-time":"2009-08-01T00:00:00Z","timestamp":1249084800000},"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":[[2009,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Current evidence suggests that protective antigen (PA)-based anthrax vaccines may elicit a narrow neutralizing antibody repertoire, and this may represent a vulnerability with PA-based vaccines. In an effort to identify neutralizing specificities which may complement those prevalent in PA antiserum, we evaluated whether sequences within the 2\u03b22-2\u03b23 loop of PA, which are apparent in the crystal structure of heptameric but not monomeric PA, might represent a target for an epitope-specific vaccine for anthrax and, further, whether antibodies to these sequences are induced in rabbits immunized with monomeric PA. We evaluated the immunogenicity in rabbits of a multiple antigenic peptide (MAP) displaying copies of amino acids (aa) 305 to 319 of this region. Overall, four out of six rabbits vaccinated with the MAP peptide in Freund's adjuvant developed high-titer, high-avidity antibody responses which cross-reacted with the immobilized peptide sequence comprising aa 305 to 319 and with PA, as determined by an enzyme-linked immunosorbent assay, and which displayed potent and durable neutralization of lethal toxin (LeTx) in vitro, with peak titers which were 452%, 100%, 67%, and 41% of the peak neutralization titers observed in positive-control rabbits immunized with PA. Importantly, analysis of sera from multiple cohorts of rabbits with high-titer immunity to PA demonstrated a virtual absence of this potent antibody specificity, and work by others suggests that this specificity may be present at only low levels in primate PA antiserum. These results highlight the potential importance of this immunologically cryptic neutralizing epitope from PA as a target for alternative and adjunctive vaccines for anthrax.<\/jats:p>","DOI":"10.1128\/iai.00358-09","type":"journal-article","created":{"date-parts":[[2009,6,2]],"date-time":"2009-06-02T00:58:56Z","timestamp":1243904336000},"page":"3380-3388","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Synthetic Peptide Vaccine Targeting a Cryptic Neutralizing Epitope in Domain 2 of<i>Bacillus anthracis<\/i>Protective Antigen"],"prefix":"10.1128","volume":"77","author":[{"given":"Jon","family":"Oscherwitz","sequence":"first","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48105"},{"name":"Veterans Affairs Medical Center, 2215 Fuller Road, Ann Arbor, Michigan 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana L.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Te-Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Joseph Stokes Jr. Research Institute, Children's Hospital of Philadelphia, Abramson Research Center, Room 1216B, 3615 Civic Center Blvd., Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Joseph Stokes Jr. Research Institute, Children's Hospital of Philadelphia, Abramson Research Center, Room 1216B, 3615 Civic Center Blvd., Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kemp B.","family":"Cease","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48105"},{"name":"Veterans Affairs Medical Center, 2215 Fuller Road, Ann Arbor, Michigan 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00015-08"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00261-07"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/515298"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2024"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.9.6006-6013.1994"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03087"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.11.6313-6317.2004"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.01.068"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.19.111301.140655"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(98)00023-1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5364.734"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"673","DOI":"10.4049\/jimmunol.106.3.673","volume":"106","year":"1971","unstructured":"Edgington, T. 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