{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:23:04Z","timestamp":1778584984710,"version":"3.51.4"},"reference-count":89,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"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":["Microbiol Mol Biol Rev"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:sec><jats:title>SUMMARY<\/jats:title><jats:p>The intentional use of<jats:italic>Bacillus anthracis<\/jats:italic>, the etiological agent of anthrax, as a bioterrorist weapon in late 2001 made our society acutely aware of the importance of developing, testing, and stockpiling adequate countermeasures against biological attacks. Biodefense vaccines are an important component of our arsenal to be used during a biological attack. However, most of the agents considered significant threats either have been eradicated or rarely infect humans alive today. As such, vaccine efficacy cannot be determined in human clinical trials but must be extrapolated from experimental animal models. This article reviews the efficacy and immunogenicity of human anthrax vaccines in well-defined animal models and the progress toward developing a rugged immunologic correlate of protection. The ongoing evaluation of human anthrax vaccines will be dependent on animal efficacy data in the absence of human efficacy data for licensure by the U.S. Food and Drug Administration.<\/jats:p><\/jats:sec>","DOI":"10.1128\/mmbr.68.4.617-629.2004","type":"journal-article","created":{"date-parts":[[2004,12,8]],"date-time":"2004-12-08T18:16:59Z","timestamp":1102529819000},"page":"617-629","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":60,"title":["Rabbit and Nonhuman Primate Models of Toxin-Targeting Human Anthrax Vaccines"],"prefix":"10.1128","volume":"68","author":[{"given":"Andrew J.","family":"Phipps","sequence":"first","affiliation":[{"name":"Department of Veterinary Biosciences"},{"name":"Center for Microbial Interface Biology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Premanandan","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences"},{"name":"Center for Microbial Interface Biology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy E.","family":"Barnewall","sequence":"additional","affiliation":[{"name":"Medical Research Evaluation Facility, Battelle Memorial Institute, Columbus, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Lairmore","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences"},{"name":"Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Solove Research Institute"},{"name":"Department of Molecular Virology, Immunology, and Medical Genetics"},{"name":"Center for Retrovirus Research, Ohio State University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.6.2291"},{"key":"e_1_3_2_3_2","first-page":"1055","volume":"35","year":"1959","unstructured":"Albrink, W. S. and R. J. Goodlow. 1959. Experimental inhalation anthrax in the chimpanzee. Am. J. Pathol.35:1055-1065.","journal-title":"Am. J. Pathol."},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4049\/jimmunol.75.2.129","volume":"75","year":"1955","unstructured":"Auerbach, S. and G. G. Wright. 1955. Studies on immunity in anthrax. VI. Immunizing activity of protective antigen against various strains of Bacillus anthracis. J. Immunol.75:129-133.","journal-title":"J. Immunol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-8244(03)00085-3"},{"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":"10.1001\/jama.287.7.863"},{"key":"e_1_3_2_8_2","first-page":"476","volume":"271","year":"1956","unstructured":"Belton, F. C., H. M. Darlow, and D. W. Henderson. 1956. The use of anthrax antigen to immunise man and monkey. Lancet271:476-479.","journal-title":"Lancet"},{"key":"e_1_3_2_9_2","first-page":"156","volume":"37","year":"1956","unstructured":"Belton, F. C., and D. W. Henderson. 1956. A method for assaying anthrax immunising antigen and antibody. Br. J. Exp. Pathol.37:156-160.","journal-title":"Br. J. Exp. Pathol."},{"key":"e_1_3_2_10_2","first-page":"144","volume":"35","year":"1954","unstructured":"Belton, F. C., and R. E. Strange. 1954. Studies on a protective antigen produced in vitro from Bacillus anthracis: medium and methods of production. Br. J. Exp. Pathol.35:144-152.","journal-title":"Br. J. Exp. Pathol."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.20.2554"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5636"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.52.4.632"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1980.tb18910.x"},{"key":"e_1_3_2_15_2","first-page":"95","year":"1998","unstructured":"Brachman, P. S., and A. F. Kaufmann. 1998. Anthrax, p. 95-107. In A. S. Evans and P. S. Brachman (ed.), Bacterial infections of humans. Plenum Medical Book Co., New York, N.Y.","journal-title":"Bacterial infections of humans"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.3.1212-1218.2003"},{"key":"e_1_3_2_17_2","first-page":"60","volume":"275","year":"1996","unstructured":"Cole, L. A. 1996. The specter of biological weapons. Sci. Am.275:60-65.","journal-title":"Sci. Am."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00191-3"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0810.020330"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909093411107"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0022172400015795"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5364.734"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00021-4"},{"key":"e_1_3_2_24_2","unstructured":"Finney D. J. 1971. Probit analysis. Cambridge University Press Cambridge United Kingdom."},{"key":"e_1_3_2_25_2","unstructured":"Fisher L. D. and G. van Belle. 1993. Biostatistics\u2014a methodology for the health sciences. John Wiley & Sons Inc. New York N.Y."},{"key":"e_1_3_2_26_2","unstructured":"Food and Drug Administration. 2002. New drug and biological drug products; evidence needed to demonstrate effectiveness of new drugs when human efficacy studies are not ethical or feasible. 21 CFR 314 and 601. U.S. Food and Drug Administration Department of Health and Human Services Rockville Md."},{"key":"e_1_3_2_27_2","first-page":"335","volume":"20","year":"2000","unstructured":"Friedlander, A. M. 2000. Anthrax: clinical features, pathogenesis, and potential biological warfare threat. Curr. Clin. Top. Infect. Dis.20:335-349.","journal-title":"Curr. Clin. Top. Infect. Dis."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.22.2104"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/167.5.1239"},{"key":"e_1_3_2_30_2","first-page":"691","volume":"73","year":"1995","unstructured":"Fritz, D. L., N. K. Jaax, W. B. Lawrence, K. J. Davis, M. L. Pitt, J. W. Ezzell, and A. M. Friedlander. 1995. Pathology of experimental inhalation anthrax in the rhesus monkey. Lab. Investig.73:691-702.","journal-title":"Lab. Investig."},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1189\/jlb.72.6.1234","volume":"72","year":"2002","unstructured":"Gao, J. J., V. Diesl, T. Wittmann, D. C. Morrison, J. L. Ryan, S. N. Vogel, and M. T. Follettie. 2002. Regulation of gene expression in mouse macrophages stimulated with bacterial CpG-DNA and lipopolysaccharide. J. Leukoc. Biol.72:1234-1245.","journal-title":"J. Leukoc. Biol."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00207-4"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/br.30.3.657-659.1966"},{"key":"e_1_3_2_34_2","first-page":"416","volume":"44","year":"1963","unstructured":"Gleiser, C. A., C. C. Berdjis, H. A. Hartman, and W. S. Gochenour. 1963. Pathology of experimental respiratory anthrax in Macaca mulatta. Br. J. Exp. Pathol.44:416-426.","journal-title":"Br. J. Exp. Pathol."},{"key":"e_1_3_2_35_2","first-page":"54","year":"1987","unstructured":"Golub, E. S. 1987. Heterogeneity of Immunoglobulins, p. 54-72. In E. S. Golub (ed.), Immunology: a synthesis. Sinauer Associates, Inc., Sunderland, Mass.","journal-title":"Immunology: a synthesis"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880337"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/es60130a004"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.1999.00891.x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(99)01507-3"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0022172400044272"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0906.020668"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.10.4432-4439.1994"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.18.1735"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.17.2236"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(95)00139-R"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(94)90027-2"},{"key":"e_1_3_2_47_2","first-page":"125","volume":"87","year":"1996","unstructured":"Ivins, B. E., P. F. Fellows, M. L. M. Pitt, J. E. Estep, S. L. Welkos, P. L. Worsham, and A. M. Friedlander. 1996. Efficacy of a standard human anthrax vaccine against Bacillus anthracis aerosol spore challenge in rhesus macaques. Salisbury Med. Bull.87:125-126.","journal-title":"Salisbury Med. Bull."},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(98)80112-6"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0810.020353"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209279200"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.2.544-550.2002"},{"key":"e_1_3_2_52_2","first-page":"143","volume":"271","year":"2002","unstructured":"Koehler, T. M. 2002. Bacillus anthracis genetics and virulence gene regulation. Curr. Top. Microbiol. Immunol.271:143-164.","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.6.3.352-355.1999"},{"key":"e_1_3_2_54_2","first-page":"956","volume":"54","year":"1978","unstructured":"LaForce, F. M. 1978. Woolsorters' disease in England. Bull. N. Y. Acad. Med.54:956-963.","journal-title":"Bull. N. Y. Acad. Med."},{"key":"e_1_3_2_55_2","first-page":"543","year":"1995","unstructured":"Leppla, S. H. 1995. Anthrax toxins, p. 543-572. In J. Moss, B. Iglewski, M. Vaughan and A. T. Tu (ed.), Bacterial toxins and virulence factors in disease. Matcel Dekker, Inc., New York, N.Y.","journal-title":"Bacterial toxins and virulence factors in disease"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.12.5171-5175.1997"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2003.07.004"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.52.2.509-512.1986"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.7.1807-1813.1988"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-142-3-707"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0602-597"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(97)00268-5"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1177\/096228029200100103"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7973702"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.39.1.371-376.1983"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.47.1.306-310.1985"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.20.6509-6515.1999"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073163"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.158.5.429"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00234-1"},{"key":"e_1_3_2_71_2","unstructured":"Pitt M. L. M. B. Ivins J. E. Estep J. Farchaus and A. Friedlander. 1996. Comparative efficacy of a recombinant protective antigen vaccine against inhalation anthrax in guinea pigs rabbits and rhesus monkeys. Abstr. 96th. Gen. Meet. Am. Soc. Microbiol. 1996 abstr. E-70 p. 278."},{"key":"e_1_3_2_72_2","first-page":"130","volume":"87","year":"1996","unstructured":"Pitt, M. L. M., B. E. Ivins, J. E. Estep, J. Farchaus, and A. M. Friedlander. 1996. Comparison of the efficacy of purified protective antigen and MDPH (anthrax vaccine adsorbed) to protect non-human primates from inhalation anthrax. Salisbury Med. Bull.87:130.","journal-title":"Salisbury Med. Bull."},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00174-2"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0810.020380"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.10134"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.5.2888-2893.2001"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.6.6.953-958.1999"},{"key":"e_1_3_2_78_2","first-page":"474","volume":"267","year":"1954","unstructured":"Smith, H., J. Keppie, and J. L. Stanley. 1954. Observations on the cause of death in experimental anthrax. Lancet267:474-476.","journal-title":"Lancet"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408367809150920"},{"key":"e_1_3_2_80_2","first-page":"153","volume":"35","year":"1954","unstructured":"Strange, R. E. and F. C. Belton. 1954. Studies on a protective antigen produced in vitro from Bacillus anthracis: purification and chemistry of the antigen. Br. J. Exp. Pathol.35:153-165.","journal-title":"Br. J. Exp. Pathol."},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.170.5.2263-2266.1988"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.52.2.356-363.1986"},{"key":"e_1_3_2_83_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_84_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302837200"},{"key":"e_1_3_2_85_2","first-page":"1201","volume":"88","year":"2003","unstructured":"Vasconcelos, D., R. Barnewall, M. Babin, R. Hunt, J. Estep, C. Nielsen, R. Carnes, and J. Carney. 2003. Pathology of inhalation anthrax in cynomolgus monkeys (Macaca fascicularis). Lab. Investig.88:1201-1209.","journal-title":"Lab. Investig."},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-51-10-821"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-147-6-1677"},{"key":"e_1_3_2_88_2","doi-asserted-by":"crossref","first-page":"387","DOI":"10.4049\/jimmunol.73.6.387","volume":"73","year":"1954","unstructured":"Wright, G. G., T. W. Green, and R. G. Kanode, Jr. 1954. Studies on immunity in anthrax. V. Immunizing activity of alum-precipitated protective antigen. J. Immunol.73:387-391.","journal-title":"J. Immunol."},{"key":"e_1_3_2_89_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.4049\/jimmunol.72.4.263","volume":"72","year":"1954","unstructured":"Wright, G. G., M. A. Hedberg, and J. B. Slein. 1954. Studies on immunity in anthrax. III. Elaboration of protective antigen in a chemically defined, non-protein medium. J. Immunol.72:263-269.","journal-title":"J. Immunol."},{"key":"e_1_3_2_90_2","first-page":"982","volume":"122","year":"1998","unstructured":"Zaucha, G. M., L. M. Pitt, J. Estep, B. E. Ivins, and A. M. Friedlander. 1998. The pathology of experimental anthrax in rabbits exposed by inhalation and subcutaneous inoculation. Arch. Pathol. Lab. Med.122:982-992.","journal-title":"Arch. Pathol. Lab. Med."}],"container-title":["Microbiology and Molecular Biology Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/MMBR.68.4.617-629.2004","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/MMBR.68.4.617-629.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T19:08:51Z","timestamp":1682881731000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/MMBR.68.4.617-629.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12]]},"references-count":89,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,12]]}},"alternative-id":["10.1128\/MMBR.68.4.617-629.2004"],"URL":"https:\/\/doi.org\/10.1128\/mmbr.68.4.617-629.2004","relation":{},"ISSN":["1092-2172","1098-5557"],"issn-type":[{"value":"1092-2172","type":"print"},{"value":"1098-5557","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12]]},"assertion":[{"value":"2004-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}