Progress and obstacles in vaccine development for the ehrlichioses.
Ehrlichia are tick-borne obligately intracellular bacteria that cause significant diseases in veterinary natural hosts, including livestock and companion animals, and are now considered important zoonotic pathogens in humans. Vaccines are needed for these veterinary and zoonotic human pathogens, but many obstacles exist that have impeded their development. These obstacles include understanding genetic and antigenic variability, influence of the host on the pathogen phenotype and immunogenicity, identification of the ehrlichial antigens that stimulate protective immunity and those that elicit immunopathology, development of animal models that faithfully reflect the immune responses of the hosts and understanding molecular host-pathogen interactions involved in immune evasion or that may be blocked by the host immune response. We review the obstacles and progress in addressing barriers associated with vaccine development to protect livestock, companion animals and humans against these host defense-evasive and cell function-manipulative, vector-transmitted pathogens.
McBride
Jere W
JW
Department of Pathology, Center for Emerging Infectious Diseases and Biodefense, Sealy Center for Vaccine Development, and the Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-0609, USA. jemcbrid@utmb.edu
Walker
David H
DH
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D035843:Biomedical Research / Q000639:trends; D004195:Disease Models, Animal; D004536:Ehrlichia / Q000276:immunology*; D016873:Ehrlichiosis / Q000517:prevention & control* / Q000662:veterinary*; D014644:Genetic Variation; D054884:Host-Pathogen Interactions; D006801:Humans; D015047:Zoonoses
D000942:Antigens, Bacterial; D001428:Bacterial Vaccines
Onderstepoort J Vet Res. 1987 Sep;54(3):165-9
3329308
Infect Immun. 2007 Jan;75(1):135-45
17060466
Emerg Infect Dis. 1999 Sep-Oct;5(5):635-42
10511519
Infect Immun. 2000 Apr;68(4):2187-95
10722619
Vet Immunol Immunopathol. 2004 Mar;98(1-2):49-57
15127841
Ann N Y Acad Sci. 2005 Dec;1063:433-5
16481555
Infect Immun. 2007 Oct;75(10):4900-8
17682040
Onderstepoort J Vet Res. 1987 Sep;54(3):405-17
3329328
Infect Immun. 2002 Apr;70(4):1824-31
11895944
Infect Genet Evol. 2009 Dec;9(6):1320-8
19712754
Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):838-43
15637156
Am J Trop Med Hyg. 1994 Jan;50(1):52-8
8304572
Clin Microbiol Rev. 2003 Jan;16(1):37-64
12525424
Onderstepoort J Vet Res. 1970 Sep;37(3):147-9
4115284
Infect Immun. 2007 Sep;75(9):4608-20
17562770
Gene. 2000 Aug 22;254(1-2):245-52
10974556
Infect Immun. 1998 May;66(5):1855-60
9573061
Onderstepoort J Vet Res. 1991 Sep;58(3):171-9
1923379
Am J Med. 1993 Oct;95(4):351-7
8213865
Cell Microbiol. 2006 Sep;8(9):1475-87
16922866
J Bacteriol. 2006 Apr;188(7):2533-42
16547041
Am J Vet Res. 1975 Jul;36(7):937-40
1147359
J Parasitol. 2002 Aug;88(4):800-1
12197136
Vet Immunol Immunopathol. 2002 Feb;85(1-2):23-32
11867164
J Clin Microbiol. 1999 Apr;37(4):1137-43
10074538
Infect Immun. 2006 Mar;74(3):1846-56
16495559
Ann N Y Acad Sci. 2006 Oct;1078:110-7
17114689
Am J Vet Res. 1982 Jul;43(7):1279-82
6808870
Infect Immun. 2007 Oct;75(10):4933-41
17664264
Infect Immun. 2006 Sep;74(9):5014-22
16926392
Infect Immun. 2003 Jan;71(1):187-95
12496165
Ann N Y Acad Sci. 2005 Dec;1063:395-402
16481547
Ann N Y Acad Sci. 2003 Jun;990:678-84
12860706
J Parasitol. 2000 Oct;86(5):983-92
11128522
Infect Immun. 2009 May;77(5):1734-45
19273555
Infect Immun. 2009 Oct;77(10):4243-55
19651857
Infect Immun. 1997 Jul;65(7):2890-7
9199464
Vet Immunol Immunopathol. 1996 Sep;53(1-2):61-71
8941969
J Vet Intern Med. 1998 Mar-Apr;12(2):61-70
9560760
Vet Parasitol. 2000 Nov 10;93(2):159-72
11035234
J Clin Microbiol. 1997 Oct;35(10):2496-502
9316896
Vaccine. 2007 Mar 8;25(12):2316-24
17224211
Infect Immun. 2006 Aug;74(8):4856-64
16861674
J Wildl Dis. 2008 Apr;44(2):381-7
18436670
Microb Pathog. 2000 Feb;28(2):71-80
10644493
N Engl J Med. 1987 Apr 2;316(14):853-6
3029590
Onderstepoort J Vet Res. 1984 Dec;51(4):275-6
6533520
Infect Immun. 2003 May;71(5):2516-24
12704123
Vet Microbiol. 2007 Sep 20;124(1-2):58-65
17459616
Ann N Y Acad Sci. 2002 Oct;969:151-4
12381581
J Clin Microbiol. 2000 Oct;38(10):3705-9
11015387
Microbiology (Reading). 1994 Aug;140 ( Pt 8):2135-42
7921263
J Parasitol. 2000 Oct;86(5):1135-6
11128494
Microbes Infect. 2010 May;12(5):337-45
20116446
Infect Immun. 2009 Jun;77(6):2304-10
19307215
Annu Rev Entomol. 2003;48:307-37
12414740
Vet Parasitol. 2010 Feb 10;167(2-4):123-35
19836892
J Clin Microbiol. 1994 Sep;32(9):2107-12
7814533
Rev Elev Med Vet Pays Trop. 1993;46(1-2):197-201
8134632
J Clin Microbiol. 2000 Jan;38(1):369-74
10618118
Infect Immun. 2007 Jul;75(7):3604-13
17438035
Clin Diagn Lab Immunol. 1997 Nov;4(6):731-5
9384299
Infect Immun. 1998 Jun;66(6):2514-20
9596710
Infect Immun. 1994 Feb;62(2):747-50
8300237
Dev Biol Stand. 1998;92:309-15
9554286
Vet Microbiol. 2008 Apr 1;128(1-2):136-47
18006251
JAMA. 1990 Nov 7;264(17):2251-8
2214103
Infect Immun. 2009 Jan;77(1):245-54
19001077
Am J Vet Res. 1990 Jun;51(6):929-31
2368951
Antimicrob Agents Chemother. 1998 Feb;42(2):362-8
9527787
J Immunol. 2006 Oct 1;177(7):4644-51
16982903
Am J Pathol. 2001 Feb;158(2):757-69
11159213
Infect Immun. 1998 Jan;66(1):132-9
9423849
J Immunol. 2004 Feb 1;172(3):1786-800
14734762
Clin Infect Dis. 2001 Nov 1;33(9):1586-94
11568857
Gene. 2001 Sep 19;275(2):287-98
11587856
J Immunol. 2002 Aug 1;169(3):1419-25
12133967
Vet Microbiol. 2007 Jun 21;122(3-4):298-305
17321077
Gene. 1997 Jan 15;184(2):149-54
9031621
Infect Immun. 2008 Apr;76(4):1434-44
18212072
J Clin Microbiol. 1996 Sep;34(9):2133-9
8862572
J Clin Microbiol. 1992 Apr;30(4):775-80
1374076
Vaccine. 2008 Aug 12;26(34):4363-71
18602727
Infect Immun. 2003 Sep;71(9):5324-31
12933880
Vet Microbiol. 2007 Feb 25;120(1-2):158-66
17123750
Infect Immun. 2008 Apr;76(4):1572-80
18212082
Parasite Immunol. 1996 Jun;18(6):317-24
9229384
J Clin Microbiol. 1993 Oct;31(10):2729-37
8253974
Infect Immun. 2004 Jan;72(1):498-507
14688131
Infect Immun. 2005 Jan;73(1):79-87
15618143
Vet Microbiol. 2008 Jan 1;126(1-3):189-99
17646061
Ann N Y Acad Sci. 1998 Jun 29;849:372-4
9668489
J Am Vet Med Assoc. 1982 Aug 1;181(3):236-8
7050062
Infect Immun. 1998 Aug;66(8):3892-9
9673277
J Clin Microbiol. 1998 Jan;36(1):73-6
9431923
Clin Diagn Lab Immunol. 2003 Jul;10(4):520-4
12853379
Infect Immun. 1997 Jan;65(1):236-41
8975917
J Immunol. 2001 Feb 1;166(3):1855-62
11160232
Adv Vet Sci Comp Med. 1983;27:427-80
6359836
Vet Microbiol. 2002 Mar 22;85(3):259-73
11852193
Infect Immun. 2008 May;76(5):1920-30
18285501
J Clin Microbiol. 1999 May;37(5):1447-53
10203503
Ann N Y Acad Sci. 2002 Oct;969:269-74
12381604
Clin Vaccine Immunol. 2010 Jan;17(1):87-97
19955322
J Parasitol. 2000 Feb;86(1):44-9
10701562
J Bacteriol. 2006 Jun;188(11):4015-23
16707693
PLoS Genet. 2006 Feb;2(2):e21
16482227
Infect Immun. 1998 May;66(5):2115-21
9573097
J Bacteriol. 2005 Jul;187(14):4782-91
15995193
Dev Biol (Basel). 2003;114:121-36
14677683
Vet Parasitol. 2010 Feb 10;167(2-4):187-95
19819629
Infect Immun. 2007 Jan;75(1):74-82
17088359
Onderstepoort J Vet Res. 2009 Mar;76(1):81-8
19967932
BMC Infect Dis. 2008 Apr 23;8:54
18433500
Clin Vaccine Immunol. 2008 Jul;15(7):1080-8
18480237
J Clin Microbiol. 2001 Nov;39(11):4200-3
11682561
Infect Immun. 1989 Oct;57(10):3243-6
2777383
J Infect Dis. 2008 Apr 15;197(8):1110-8
18462160
J Immunol. 2004 Jun 1;172(11):6894-901
15153508
Infect Immun. 2007 Nov;75(11):5453-9
17698576
Biochem Biophys Res Commun. 1999 Apr 13;257(2):300-5
10198207
Onderstepoort J Vet Res. 1987 Sep;54(3):489-91
3329333
Rev Elev Med Vet Pays Trop. 1993;46(1-2):189-94
8134631
Ann N Y Acad Sci. 2002 Oct;969:147-50
12381580
N Engl J Med. 1999 Jul 15;341(3):148-55
10403852
Ann Intern Med. 1994 May 1;120(9):736-43
8147546
Infect Immun. 2004 Feb;72(2):966-71
14742542
Infect Immun. 2006 Jan;74(1):711-20
16369028
Infect Immun. 2005 Dec;73(12):8009-16
16299294
Infect Immun. 2001 Oct;69(10):6172-8
11553557
Vet Rec. 1969 Nov 22;85(21):587
5356929
Infect Immun. 2002 Jan;70(1):380-8
11748204
Ann N Y Acad Sci. 2006 Oct;1081:417-33
17135545
J Infect Dis. 2000 Mar;181(3):1082-8
10720534
Parasite Immunol. 2004 Feb;26(2):95-103
15225296
Clin Vaccine Immunol. 2009 Jul;16(7):982-90
19420187