{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T09:10:50Z","timestamp":1781946650722,"version":"3.54.5"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"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":[[2008,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Neutralizing antibodies to\n            <jats:italic>Bacillus anthracis<\/jats:italic>\n            protective antigen (PA), a component of anthrax toxin, mediate protection against anthrax. PA is antigenically complex and can elicit protective and nonprotective antibodies. Furthermore, vaccinated individuals demonstrate considerable variability in their antibody responses to PA. To explore the relationship between PA structure and antigenicity, we produced\n            <jats:italic>Escherichia coli<\/jats:italic>\n            strains expressing full-length PA (PA1-4), domains 2 to 4 (PA2-4), domain 1, (PA1), and domain 4 (PA4) and evaluated the immunogenicities and protective efficacies of the protein fractions in four mouse strains (strains A\/J, BALB\/c, C57BL\/6, and Swiss Webster). Immunization with PA1-4 resulted in significantly higher lethal toxin-neutralizing antibody titers than immunization with any recombinant protein (rPA) fraction of PA. The magnitude and neutralizing capacity of the antibody response to full-length PA and its fragments varied depending on the mouse strain. We found no correlation between the antibody titer and the neutralizing antibody titer for A\/J and Swiss Webster mice. In C57BL\/6 mice, antibody titers and neutralization capacity correlated for two of four rPA domain proteins tested, while BALB\/c mice displayed a similar correlation with only one rPA. By correlating the reactivity of immune sera with solvent-exposed linear peptide segments of PA, we tentatively assign the presence of four new linear B-cell epitopes in PA amino acids 121 to 150, 143 to 158, 339 to 359, and 421 to 440. We conclude that the genetic background of the host determines the relative efficacy of the antitoxin response. The results suggest that the variability observed in vaccination studies with PA-derived vaccines is a result of host heterogeneity and implies a need to develop other antigens as vaccine candidates.\n          <\/jats:p>","DOI":"10.1128\/cvi.00015-08","type":"journal-article","created":{"date-parts":[[2008,5,15]],"date-time":"2008-05-15T01:09:46Z","timestamp":1210813786000},"page":"1115-1123","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["Immunogenicity of\n            <i>Bacillus anthracis<\/i>\n            Protective Antigen Domains and Efficacy of Elicited Antibody Responses Depend on Host Genetic Background"],"prefix":"10.1128","volume":"15","author":[{"given":"Nareen","family":"Abboud","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology"},{"name":"Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Casadevall","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"},{"name":"Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1021\/bi972657b","volume":"37","year":"1998","unstructured":"Benson, E. L., P. D. Huynh, A. Finkelstein, and R. J. Collier. 1998. Identification of residues lining the anthrax protective antigen channel. Biochemistry37:3941-3948.","journal-title":"Biochemistry"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1073\/pnas.86.7.2209","volume":"86","year":"1989","unstructured":"Blaustein, R. O., T. M. Koehler, R. J. Collier, and A. Finkelstein. 1989. Anthrax toxin: channel-forming activity of protective antigen in planar phospholipid bilayers. Proc. Natl. Acad. Sci. USA86:2209-2213.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.11.6313-6317.2004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.4.1781-1786.2000"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrd1694","volume":"4","year":"2005","unstructured":"Burnett, J. C., E. A. Henchal, A. L. Schmaljohn, and S. Bavari. 2005. The evolving field of biodefence: therapeutic developments and diagnostics. Nat. Rev. Drug Discov.4:281-297.","journal-title":"Nat. Rev. Drug Discov."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.10.3700-3707.1991"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1056\/NEJM199909093411107","volume":"341","year":"1999","unstructured":"Dixon, T. C., M. Meselson, J. Guillemin, and P. C. Hanna. 1999. Anthrax. N. Engl. J. Med.341:815-826.","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.3.1653-1656.2002"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.micpath.2004.10.007","volume":"38","year":"2005","unstructured":"Flick-Smith, H. C., E. L. Waters, N. J. Walker, J. Miller, A. J. Stagg, M. Green, and E. D. Williamson. 2005. Mouse model characterisation for anthrax vaccine development: comparison of one inbred and one outbred mouse strain. Microb. Pathog.38:33-40.","journal-title":"Microb. Pathog."},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1046\/j.1365-2672.1999.00898.x","volume":"87","year":"1999","unstructured":"Fowler, K., B. W. McBride, P. C. Turnbull, and L. W. Baillie. 1999. Immune correlates of protection against anthrax. J. Appl. Microbiol.87:305.","journal-title":"J. Appl. Microbiol."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.5.1066-1069.1988"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1111\/j.1574-695X.2006.00114.x","volume":"47","year":"2006","unstructured":"Gubbins, M. J., J. D. Berry, C. R. Corbett, J. Mogridge, X. Y. Yuan, L. Schmidt, B. Nicolas, A. Kabani, and R. S. Tsang. 2006. Production and characterization of neutralizing monoclonal antibodies that recognize an epitope in domain 2 of Bacillus anthracis protective antigen. FEMS Immunol. Med. Microbiol.47:436-443.","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.13.2.208-213.2006"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.6.1961-1965.1991"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/BF00152686","volume":"4","year":"1988","unstructured":"Ivins, B. E., and S. L. Welkos. 1988. Recent advances in the development of an improved, human anthrax vaccine. Eur. J. Epidemiol.4:12-19.","journal-title":"Eur. J. Epidemiol."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.58.2.303-308.1990"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.2.662-668.1992"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"5042","DOI":"10.1073\/pnas.0401351101","volume":"101","year":"2004","unstructured":"Kozel, T. R., W. J. Murphy, S. Brandt, B. R. Blazar, J. A. Lovchik, P. Thorkildson, A. Percival, and C. R. Lyons. 2004. mAbs to Bacillus anthracis capsular antigen for immunoprotection in anthrax and detection of antigenemia. Proc. Natl. Acad. Sci. USA101:5042-5047.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"13147","DOI":"10.1073\/pnas.0405405101","volume":"101","year":"2004","unstructured":"Lacy, D. B., D. J. Wigelsworth, R. A. Melnyk, S. C. Harrison, and R. J. Collier. 2004. Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation. Proc. Natl. Acad. Sci. USA101:13147-13151.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.12.5171-5175.1997"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.7.1807-1813.1988"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1099\/13500872-142-3-707","volume":"142","year":"1996","unstructured":"Little, S. F., J. M. Novak, J. R. Lowe, S. H. Leppla, Y. Singh, K. R. Klimpel, B. C. Lidgerding, and A. M. Friedlander. 1996. Characterization of lethal factor binding and cell receptor binding domains of protective antigen of Bacillus anthracis using monoclonal antibodies. Microbiology142(Pt 3):707-715.","journal-title":"Microbiology"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1023\/A:1021916500286","volume":"134","year":"2002","unstructured":"Masnaya, N. V., A. A. Churin, O. S. Borsuk, and E. Y. Sherstoboev. 2002. Immune reactions in different mouse strains. Bull. Exp. Biol Med.134:376-378.","journal-title":"Bull. Exp. Biol Med."},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nbt0602-597","volume":"20","year":"2002","unstructured":"Maynard, J. A., C. B. Maassen, S. H. Leppla, K. Brasky, J. L. Patterson, B. L. Iverson, and G. Georgiou. 2002. Protection against anthrax toxin by recombinant antibody fragments correlates with antigen affinity. Nat. Biotechnol.20:597-601.","journal-title":"Nat. Biotechnol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/S0264-410X(97)00268-5","volume":"16","year":"1998","unstructured":"McBride, B. W., A. Mogg, J. L. Telfer, M. S. Lever, J. Miller, P. C. Turnbull, and L. Baillie. 1998. Protective efficacy of a recombinant protective antigen against Bacillus anthracis challenge and assessment of immunological markers. Vaccine16:810-817.","journal-title":"Vaccine"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.2.1009-1015.2006"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"10432","DOI":"10.1021\/bi990792d","volume":"38","year":"1999","unstructured":"Miller, C. J., J. L. Elliott, and R. J. Collier. 1999. Anthrax protective antigen: prepore-to-pore conversion. Biochemistry38:10432-10441.","journal-title":"Biochemistry"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"20607","DOI":"10.1016\/S0021-9258(17)32036-7","volume":"269","year":"1994","unstructured":"Milne, J. C., D. Furlong, P. C. Hanna, J. S. Wall, and R. J. Collier. 1994. Anthrax protective antigen forms oligomers during intoxication of mammalian cells. J. Biol. Chem.269:20607-20612.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1146\/annurev.micro.55.1.647","volume":"55","year":"2001","unstructured":"Mock, M., and A. Fouet. 2001. Anthrax. Annu. Rev. Microbiol.55:647-671.","journal-title":"Annu. Rev. Microbiol."},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.6.2111-2116.2001"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.6.3276-3283.2004"},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/385833a0","volume":"385","year":"1997","unstructured":"Petosa, C., R. J. Collier, K. R. Klimpel, S. H. Leppla, and R. C. Liddington. 1997. Crystal structure of the anthrax toxin protective antigen. Nature385:833-838.","journal-title":"Nature"},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1046\/j.1365-2672.1999.00897.x","volume":"87","year":"1999","unstructured":"Pitt, M. L., S. Little, B. E. Ivins, P. Fellows, J. Boles, J. Barth, J. Hewetson, and A. M. Friedlander. 1999. In vitro correlate of immunity in an animal model of inhalational anthrax. J. Appl. Microbiol.87:304.","journal-title":"J. Appl. Microbiol."},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.5.2888-2893.2001"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00150-06"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"30936","DOI":"10.1074\/jbc.M301154200","volume":"278","year":"2003","unstructured":"Rosovitz, M. J., P. Schuck, M. Varughese, A. P. Chopra, V. Mehra, Y. Singh, L. M. McGinnis, and S. H. Leppla. 2003. Alanine-scanning mutations in domain 4 of anthrax toxin protective antigen reveal residues important for binding to the cellular receptor and to a neutralizing monoclonal antibody. J. Biol. Chem.278:30936-30944.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"8945","DOI":"10.1073\/pnas.1633512100","volume":"100","year":"2003","unstructured":"Schneerson, R., J. Kubler-Kielb, T. Y. Liu, Z. D. Dai, S. H. Leppla, A. Yergey, P. Backlund, J. Shiloach, F. Majadly, and J. B. Robbins. 2003. Poly(gamma-d-glutamic acid) protein conjugates induce IgG antibodies in mice to the capsule of Bacillus anthracis: a potential addition to the anthrax vaccine. Proc. Natl. Acad. Sci. USA100:8945-8950.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1126\/science.109563","volume":"292","year":"2001","unstructured":"Sellman, B. R., M. Mourez, and R. J. Collier. 2001. Dominant-negative mutants of a toxin subunit: an approach to therapy of anthrax. Science292:695-697.","journal-title":"Science"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"11099","DOI":"10.1016\/S0021-9258(18)60433-8","volume":"264","year":"1989","unstructured":"Singh, Y., S. H. Leppla, R. Bhatnagar, and A. M. Friedlander. 1989. Internalization and processing of Bacillus anthracis lethal toxin by toxin-sensitive and -resistant cells. J. Biol. Chem.264:11099-11102.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/j.1365-3083.2006.01891.x","volume":"65","year":"2007","unstructured":"Sinha, P., J. A. Snyder, E. Y. Kim, and K. D. Moudgil. 2007. The major histocompatibility complex haplotypes dictate and the background genes fine-tune the dominant versus the cryptic response profile of a T-cell determinant within a native antigen: relevance to disease susceptibility and vaccination. Scand. J. Immunol.65:158-165.","journal-title":"Scand. J. Immunol."},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01242-06"},{"key":"e_1_3_2_43_2","first-page":"397","volume":"29","year":"2000","unstructured":"Subramanian, S., J. Rao, P. Jyothi, and P. R. Adiga. 2000. Strain-dependent variability in immune response to chicken riboflavin carrier protein in mice with different haplotypes. Immunol. Investig.29:397-409.","journal-title":"Immunol. Investig."},{"key":"e_1_3_2_44_2","first-page":"239","volume":"66","year":"1993","unstructured":"Tokunaga, Y., C. Hiramine, M. Itoh, A. Mukasa, and K. Hojo. 1993. Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. I. Comparison of pathology, delayed type hypersensitivity, and antibody. Clin. Immunol. Immunopathol.66:239-247.","journal-title":"I. Comparison of pathology, delayed type hypersensitivity, and antibody. Clin. Immunol. Immunopathol."},{"key":"e_1_3_2_45_2","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/0264-410X(91)90237-Z","volume":"9","year":"1991","unstructured":"Turnbull, P. C. 1991. Anthrax vaccines: past, present and future. Vaccine9:533-539.","journal-title":"Vaccine"},{"key":"e_1_3_2_46_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. (Berlin)177:293-303.","journal-title":"Med. Microbiol. Immunol. (Berlin)"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.4.1860-1865.1999"},{"key":"e_1_3_2_48_2","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1126\/science.168.3933.852","volume":"168","year":"1970","unstructured":"Vaz, N. M., and B. B. Levine. 1970. Immune responses of inbred mice to repeated low doses of antigen: relationship to histocompatibility (H-2) type. Science168:852-854.","journal-title":"Science"},{"key":"e_1_3_2_49_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1046\/j.1365-2672.1999.00901.x","volume":"87","year":"1999","unstructured":"Williamson, E. D., R. J. Beedham, A. M. Bennett, S. D. Perkins, J. Miller, and L. W. Baillie. 1999. Presentation of protective antigen to the mouse immune system: immune sequelae. J. Appl. Microbiol.87:315-317.","journal-title":"J. Appl. Microbiol."},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5978-5987.2005"},{"key":"e_1_3_2_51_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1586\/14760584.7.1.55","volume":"7","year":"2008","unstructured":"Zarebski, L. M., K. Vaughan, J. Sidney, B. Peters, H. Grey, K. D. Janda, A. Casadevall, and A. Sette. 2008. Analysis of epitope information related to Bacillus anthracis and Clostridium botulinum. Expert Rev. Vaccines7:55-74.","journal-title":"Expert Rev. Vaccines"},{"key":"e_1_3_2_52_2","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1093\/intimm\/13.9.1175","volume":"13","year":"2001","unstructured":"Zhang, W., P. D. Bardwell, C. J. Woo, V. Poltoratsky, M. D. Scharff, and A. Martin. 2001. Clonal instability of V region hypermutation in the Ramos Burkitt's lymphoma cell line. Int. Immunol.13:1175-1184.","journal-title":"Int. Immunol."}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00015-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00015-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:40:53Z","timestamp":1627591253000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00015-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7]]},"references-count":51,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2008,7]]}},"alternative-id":["10.1128\/CVI.00015-08"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00015-08","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7]]},"assertion":[{"value":"2008-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-05-01","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"}}]}}