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Some immune rabbits were, however, nonresponders to the MAP. We hypothesized that the immunogen elicited suboptimal major histocompatibility complex (MHC) class II-restricted T-cell help and that introduction of a functional helper T-cell epitope would increase MHC-restricted responsiveness and the magnitude and affinity of the antibody responses. In the current study, we characterized the T- and B-cell responses to LND peptides in mice, then designed second-generation MAP immunogens for eliciting LND-specific immunity, and tested them in rabbits. The 305-319 sequence was devoid of helper T-cell epitopes in three strains of mice; however, a T-B peptide comprising aa 305 to 319, colinearly synthesized with the P30 helper epitope of tetanus toxin, elicited robust LeTx-neutralizing immunity in mice. T-B MAPs displaying B-cell epitopes 304 to 319 (MAP304) or 305 to 319 (MAP305) elicited high-titer, durable antibody responses in rabbits which exhibited potent neutralization of LeTx in vitro. All MAP304-immune rabbits demonstrated neutralization titers exceeding that of hyperimmune sera of rabbits immunized with PA in Freund's adjuvant, with peak neutralization titers 23-, 6-, and 3-fold higher than that of the PA antiserum. Overall, immunization with MAPs containing the P30 epitope elicited higher antibody and toxin neutralization titers and peptide-specific affinity than immunization with an LND MAP lacking a helper epitope. P30-containing MAP304 represents a promising LND-specific vaccine for anthrax.<\/jats:p>","DOI":"10.1128\/iai.00899-09","type":"journal-article","created":{"date-parts":[[2009,10,6]],"date-time":"2009-10-06T01:05:24Z","timestamp":1254791124000},"page":"5509-5518","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["A Heterologous Helper T-Cell Epitope Enhances the Immunogenicity of a Multiple-Antigenic-Peptide Vaccine Targeting the Cryptic Loop-Neutralizing Determinant 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":"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\/IAI.00261-07"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.12.6165"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03087"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.11.6313-6317.2004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.19.111301.140655"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5364.734"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.165.1.21-27.1986"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-142-8-200504190-00008"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/330168a0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(85)90044-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"872","DOI":"10.4049\/jimmunol.106.3.872","volume":"106","year":"1971","unstructured":"Gershon, R. 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