title: Mouse models to assess the efficacy of non-typhoidal Salmonella vaccines: revisiting the role of host innate susceptibility and routes of challenge.
abstract: Non-typhoidal Salmonella enterica (NTS) serovars Typhimurium and Enteritidis are important causes of bacterial gastroenteritis in the USA and worldwide. In sub-Saharan Africa these two serovars are emerging as agents associated with lethal invasive disease (e.g., bacteremia, meningitis). The development of NTS vaccines, based on mucosally administered live attenuated strains and parenteral non-living antigens, could diminish the NTS disease burden globally. Mouse models of S. Typhimurium and S. Enteritidis invasive disease can accelerate the development of NTS vaccines. Live attenuated NTS vaccines elicit both cellular and humoral immunity in mice and their efficacy is well established. In contrast, non-living vaccines that primarily elicit humoral immunity have demonstrated variable efficacy. An analysis of the reported studies with non-living vaccines against S. Typhimurium and S. Enteritidis reveals that efficacy is influenced by two important independent variables: (1) the innate susceptibility to NTS infection that differs dramatically between commonly used mouse strains and (2) the virulence of the NTS strain used for challenge. Protection by non-living vaccines has generally been seen only in host-pathogen interactions where a sub-lethal infection results, such as challenging resistant mice with either highly virulent or weakly virulent strains or susceptible mice with weakly virulent strains. The immunologic basis of this discrepancy and the implications for human NTS vaccine development are reviewed herein.
authors: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. rsimon@medicine.umaryland.edu
authors: Raphael
authors: R
authors: Simon
authors: Sharon M
authors: SM
authors: Tennant
authors: James E
authors: JE
authors: Galen
authors: Myron M
authors: MM
authors: Levine
references: FEMS Immunol Med Microbiol. 2002 Jul 12;33(3):165-71
references: 12110478
references: Infect Immun. 2000 Jun;68(6):3344-8
references: 10816483
references: J Bacteriol. 1968 Jun;95(6):2014-21
references: 4876124
references: Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9803-8
references: 19487686
references: Cell Microbiol. 2010 Oct;12(10):1389-97
references: 20731667
references: Microbes Infect. 2001 Nov-Dec;3(14-15):1191-200
references: 11755407
references: Infect Immun. 2005 Nov;73(11):7226-35
references: 16239517
references: J Immunol. 1999 May 1;162(9):5398-406
references: 10228017
references: J Infect Dis. 1970 Feb;121(2):113-23
references: 4905646
references: Immunology. 2009 Dec;128(4):472-83
references: 19930040
references: J Immunol. 1987 Aug 15;139(4):1253-9
references: 2440949
references: Pediatr Infect Dis J. 2009 Feb;28(2):108-13
references: 19131902
references: Immunology. 1979 Jun;37(2):311-8
references: 381178
references: Lancet. 1987 Jun 27;1(8548):1458-61
references: 2885453
references: Pediatr Infect Dis J. 2000 Apr;19(4):312-8
references: 10783021
references: Infect Immun. 1987 Mar;55(3):816-21
references: 3546142
references: Nat Rev Microbiol. 2008 Jan;6(1):53-66
references: 18026123
references: Genome Res. 2009 Dec;19(12):2279-87
references: 19901036
references: J Immunol. 1978 Sep;121(3):1010-4
references: 690428
references: Infect Immun. 1981 May;32(2):490-6
references: 6166555
references: Infect Immun. 1972 Jan;5(1):83-90
references: 4570987
references: J Exp Med. 1974 May 1;139(5):1189-203
references: 4596512
references: Adv Immunol. 2006;91:1-44
references: 16938537
references: N Engl J Med. 2003 Oct 2;349(14):1390-1
references: 14523155
references: Bacteriol Rev. 1974 Dec;38(4):371-402
references: 4613342
references: Vaccine. 1989 Dec;7(6):495-8
references: 2481908
references: PLoS Negl Trop Dis. 2010 Mar 09;4(3):e621
references: 20231882
references: J Infect Dis. 1976 Jan;133(1):72-8
references: 1107437
references: Infect Immun. 2000 Jan;68(1):46-53
references: 10603367
references: J Infect Dis. 1972 Oct;126(4):378-86
references: 4403914
references: Infect Immun. 1993 Sep;61(9):3981-4
references: 8359920
references: Pediatr Infect Dis J. 1994 Feb;13(2):122-8
references: 8190537
references: Curr Top Microbiol Immunol. 2009;337:93-127
references: 19812981
references: Can J Microbiol. 2005 Apr;51(4):319-24
references: 15980894
references: Infect Immun. 1994 Oct;62(10):4440-4
references: 7927707
references: J Immunol. 2007 May 15;178(10):6200-7
references: 17475847
references: Microbiol Immunol. 1989;33(9):699-708
references: 2555656
references: Immunology. 1997 Apr;90(4):618-25
references: 9176117
references: J Immunol. 1999 Dec 15;163(12):6769-76
references: 10586076
references: J Infect Dis. 1972 Jul;126(1):69-76
references: 4556722
references: Pediatr Infect Dis J. 1989 Jun;8(6):374-81
references: 2664693
references: J Immunol. 2006 Sep 15;177(6):3983-93
references: 16951361
references: Science. 1999 May 7;284(5416):967-70
references: 10320378
references: Cell. 1993 May 7;73(3):469-85
references: 8490962
references: Microbes Infect. 1999 Jul;1(9):719-26
references: 10611749
references: J Immunol. 1984 Aug;133(2):958-61
references: 6376631
references: Clin Infect Dis. 2004 Apr 15;38 Suppl 3:S149-56
references: 15095184
references: Nature. 1999 Oct 21;401(6755):804-8
references: 10548107
references: Scand J Infect Dis Suppl. 1980;Suppl 24:210-5
references: 6163199
references: Bull Eur Physiopathol Respir. 1983 Mar-Apr;19(2):137-42
references: 6347281
references: Curr Opin Microbiol. 2004 Feb;7(1):51-7
references: 15036140
references: Infect Immun. 1981 May;32(2):497-502
references: 7019072
references: Arch Immunol Ther Exp (Warsz). 2006 Jan-Feb;54(1):25-31
references: 16642254
references: J Exp Med. 1994 Jul 1;180(1):15-23
references: 8006579
references: BMC Microbiol. 2006 Dec 15;6:101
references: 17173674
references: J Immunol. 2002 Jun 15;168(12):6396-403
references: 12055258
references: Infect Immun. 2009 Mar;77(3):1071-82
references: 19103774
references: Pediatr Infect Dis J. 2006 Mar;25(3):230-6
references: 16511385
references: J Clin Invest. 1960 Jan;39(1):72-81
references: 16695824
references: Immunology. 1979 Jun;37(2):319-27
references: 381179
references: MMWR Morb Mortal Wkly Rep. 2010 Apr 16;59(14):418-22
references: 20395935
references: Infect Immun. 1972 Feb;5(2):191-8
references: 4628955
references: J Infect Dis. 1985 Nov;152(5):1050-6
references: 2413142
references: Trends Microbiol. 1998 Apr;6(4):135-6
references: 9587189
references: Infect Immun. 1978 Feb;19(2):575-82
references: 344216
references: Infect Immun. 1979 Sep;25(3):857-62
references: 387596
references: J Exp Med. 1999 Feb 15;189(4):615-25
references: 9989976
references: J Infect Dis. 1984 Sep;150(3):425-35
references: 6207248
references: N Engl J Med. 2005 Jan 6;352(1):39-47
references: 15635111
references: J Immunol. 2000 Feb 15;164(4):1648-52
references: 10657605
references: N Engl J Med. 2001 Apr 26;344(17):1263-9
references: 11320385
references: Infect Immun. 1970 Mar;1(3):243-50
references: 16557723
references: J Bacteriol. 1969 Feb;97(2):667-75
references: 5773020
references: J Med Microbiol. 2007 Nov;56(Pt 11):1479-1484
references: 17965348
references: Microbiol Immunol. 1994;38(7):553-9
references: 7968689
references: Immunol Cell Biol. 2009 Jul;87(5):400-12
references: 19417771
references: Infect Immun. 1997 Dec;65(12):5381-7
references: 9393846
references: Vaccine. 1993;11(2):122-5
references: 8438611
references: Infect Immun. 1983 Aug;41(2):563-9
references: 6347890
references: Curr Top Microbiol Immunol. 2009;334:179-98
references: 19521686
references: Infect Immun. 2003 Jan;71(1):30-9
references: 12496146
references: Infect Immun. 2005 Mar;73(3):1350-6
references: 15731032
references: Infect Immun. 1982 May;36(2):696-703
references: 7044974
references: Trop Med Int Health. 2009 Dec;14(12):1467-74
references: 19793081
references: J Exp Med. 2004 Jan 19;199(2):231-41
references: 14734525
references: Pediatr Infect Dis J. 2006 Aug;25(8):700-5
references: 16874169
references: J Infect Dis. 2001 Jan 15;183(2):261-268
references: 11120931
references: Infect Immun. 1992 May;60(5):1786-92
references: 1373399
references: J Immunol. 2009 Jun 15;182(12):7473-81
references: 19494270
references: J Immunol. 1984 Aug;133(2):950-7
references: 6203984
references: Gastroenterology. 1994 Oct;107(4):915-23
references: 7926481
references: Infect Immun. 1973 May;7(5):735-42
references: 4587521
references: J Bacteriol. 1969 Feb;97(2):676-83
references: 5773021
references: Infect Immun. 1972 Oct;6(4):451-8
references: 4564282
references: Microbes Infect. 2007 Nov-Dec;9(14-15):1662-70
references: 18024118
references: Vaccine. 1996 Mar;14(4):251-9
references: 8744548
references: Trans R Soc Trop Med Hyg. 2000 May-Jun;94(3):310-4
references: 10975008
references: Infect Immun. 1993 Jul;61(7):3017-25
references: 8390406
references: Bull World Health Organ. 1994;72(6):957-71
references: 7867143
references: Trends Cell Biol. 2003 Apr;13(4):204-9
references: 12667758
references: Microbiol Immunol. 1990;34(11):917-27
references: 1965322
references: Science. 1998 Dec 11;282(5396):2085-8
references: 9851930
references: Infect Immun. 1977 Sep;17(3):555-60
references: 332627
references: Immunology. 1987 Aug;61(4):535-41
references: 2450832
references: Microb Pathog. 1987 Aug;3(2):129-41
references: 2849016
references: J Med Microbiol. 2003 Jun;52(Pt 6):453-459
references: 12748263
references: J Immunol. 2005 Oct 1;175(7):4603-10
references: 16177105
references: J Bacteriol. 1967 Mar;93(3):773-8
references: 5337833
references: Lancet Infect Dis. 2009 Nov;9(11):688-98
references: 19850227
references: Infect Immun. 1992 Nov;60(11):4679-86
references: 1383154
references: Infect Immun. 1985 Mar;47(3):605-12
references: 3882560
references: Lancet Infect Dis. 2004 Dec;4(12):739-49
references: 15567123
references: Microb Pathog. 1992 Dec;13(6):477-91
references: 1363824
references: Infect Immun. 2001 Nov;69(11):6725-30
references: 11598044
references: Microb Pathog. 1991 Jul;11(1):33-8
references: 1795626
references: Infect Immun. 1979 Sep;25(3):863-72
references: 387597
references: Vaccine. 2003 Jan 17;21(5-6):401-18
references: 12531639
references: J Immunol. 2000 Jan 15;164(2):986-93
references: 10623848