title: Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations.
abstract: Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 10(8) , 2 × 10(9) and 2 × 10(10) colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 10(9) CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 10(10) CFU). The challenge dose, 2 × 10(10) CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains.
authors.affiliation: Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
authors.forename: Dilara
authors.initials: D
authors.lastname: Islam
authors.forename: Nattaya
authors.initials: N
authors.lastname: Ruamsap
authors.forename: Patchariya
authors.initials: P
authors.lastname: Khantapura
authors.forename: Ajchara
authors.initials: A
authors.lastname: Aksomboon
authors.forename: Apichai
authors.initials: A
authors.lastname: Srijan
authors.forename: Boonchai
authors.initials: B
authors.lastname: Wongstitwilairoong
authors.forename: Ladaporn
authors.initials: L
authors.lastname: Bodhidatta
authors.forename: Montip
authors.initials: M
authors.lastname: Gettayacamin
authors.forename: Malabi M
authors.initials: MM
authors.lastname: Venkatesan
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Mason
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000921:Antibody-Producing Cells / Q000276:immunology; D058491:Bacterial Load; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004405:Dysentery, Bacillary / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D008253:Macaca mulatta; D008297:Male; D022281:Shigella Vaccines / Q000008:administration & dosage*; D012762:Shigella dysenteriae / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity; D013270:Stomach
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D022281:Shigella Vaccines
keywords: Shigellosis; challenge model; rhesus monkey (Macaca mulatta)
references.citation: Bull World Health Organ. 1999;77(8):651-66
references.pmid: 10516787
references.citation: Am J Trop Med Hyg. 2006 May;74(5):891-900
references.pmid: 16687698
references.citation: Histopathology. 1994 Jan;24(1):65-71
references.pmid: 8144144
references.citation: J Immunol Methods. 2000 Sep 21;243(1-2):243-55
references.pmid: 10986418
references.citation: Philos Trans R Soc Lond B Biol Sci. 2000 May 29;355(1397):575-86
references.pmid: 10874731
references.citation: Cell Microbiol. 2003 Jul;5(7):481-91
references.pmid: 12814438
references.citation: Infect Immun. 1999 Jul;67(7):3437-43
references.pmid: 10377124
references.citation: Infect Immun. 1990 Jun;58(6):2002-4
references.pmid: 1692813
references.citation: Clin Infect Dis. 1997 Jan;24 Suppl 1:S102-5
references.pmid: 8994788
references.citation: Infect Immun. 1984 Nov;46(2):465-9
references.pmid: 6389344
references.citation: Am J Pathol. 1975 Oct;81(1):251-4
references.pmid: 810032
references.citation: Postgrad Med J. 1986 Dec;62(734):1101-5
references.pmid: 3658847
references.citation: Infect Immun. 1997 Feb;65(2):739-49
references.pmid: 9009337
references.citation: Vaccine. 2008 Jun 19;26(26):3291-6
references.pmid: 18468742
references.citation: APMIS. 1996 Jul-Aug;104(7-8):563-74
references.pmid: 8920810
references.citation: Vaccine. 2006 May 1;24(18):3762-71
references.pmid: 16098634
references.citation: Vet Pathol Suppl. 1982 Sep;19 Suppl 7:1-8
references.pmid: 6153000
references.citation: Clin Chem. 1998 Sep;44(9):2057-60
references.pmid: 9733011
references.citation: Am J Pathol. 1968 Mar;52(3):503-29
references.pmid: 4966811
references.citation: J Bacteriol. 1958 May;75(5):604-10
references.pmid: 13538931
references.citation: APMIS. 1991 Sep;99(9):787-96
references.pmid: 1892634
references.citation: Gastroenterology. 1975 Feb;68(2):270-8
references.pmid: 1090480
references.citation: Nat Rev Microbiol. 2007 Jul;5(7):540-53
references.pmid: 17558427
references.citation: J Hyg Epidemiol Microbiol Immunol. 1959;3:292-305
references.pmid: 14445016
references.citation: J Infect Dis. 1984 Dec;150(6):899-903
references.pmid: 6501931
references.citation: Microbiology (Reading). 2006 Jun;152(Pt 6):1827-1838
references.pmid: 16735745
references.citation: N Engl J Med. 1991 Apr 18;324(16):1110-8
references.pmid: 2008184
references.citation: World Health Forum. 1997;18(1):1-8
references.pmid: 9233055
references.citation: Pediatr Infect Dis J. 1989 Nov;8(11):767-72
references.pmid: 2594452
references.citation: Am J Pathol. 1986 Apr;123(1):25-38
references.pmid: 3515957
references.citation: Am J Pathol. 1967 Aug;51(2):259-67
references.pmid: 4952816
references.citation: J Clin Microbiol. 2004 May;42(5):2031-5
references.pmid: 15131166
references.citation: J Immunol. 2007 Feb 15;178(4):2476-82
references.pmid: 17277155
references.citation: Vaccine. 1993;11(8):830-6
references.pmid: 8356844
references.citation: J Clin Pathol. 1997 Jun;50(6):513-20
references.pmid: 9378821
references.citation: J Am Vet Med Assoc. 1993 Jul 1;203(1):126-32
references.pmid: 8407446
references.citation: Infect Immun. 1985 Apr;48(1):124-9
references.pmid: 3884506
references.citation: Am J Trop Med Hyg. 2009 Apr;80(4):609-14
references.pmid: 19346386
references.citation: Infect Immun. 2003 May;71(5):2684-92
references.pmid: 12704143
references.citation: Vet Rec. 1985 Apr 20;116(16):431-6
references.pmid: 3923690
references.citation: J Bacteriol. 1965 Mar;89:803-9
references.pmid: 14273664
references.citation: J Infect Dis. 1989 Jun;159(6):1126-8
references.pmid: 2656880
references.citation: J Infect Dis. 1995 Feb;171(2):376-84
references.pmid: 7531208
references.citation: J Infect Dis. 1993 Feb;167(2):458-61
references.pmid: 8421181
references.citation: J Bacteriol. 1990 Apr;172(4):1905-15
references.pmid: 1690703
references.citation: J Infect Dis. 1997 Oct;176(4):1013-8
references.pmid: 9333160
references.citation: Infect Immun. 1995 Nov;63(11):4350-7
references.pmid: 7591070
references.citation: ILAR J. 2008;49(2):220-55
references.pmid: 18323583
references.citation: FEMS Immunol Med Microbiol. 2011 Aug;62(3):304-14
references.pmid: 21539623
references.citation: J Immunol. 2009 Nov 1;183(9):5879-85
references.pmid: 19828639
references.citation: J Immunol. 2002 May 15;168(10):5240-51
references.pmid: 11994481
references.citation: Am J Clin Nutr. 1972 Dec;25(12):1427-32
references.pmid: 4629541
references.citation: FEMS Microbiol Rev. 2004 Feb;28(1):43-58
references.pmid: 14975529
references.citation: Comp Med. 2010 Feb;60(1):54-61
references.pmid: 20158950
references.citation: Vet Pathol Suppl. 1982 Sep;7:1-8
references.pmid: 6755871