title: Development of Leishmania vaccines: predicting the future from past and present experience.
abstract: Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. Resistance to infection is associated with a T-helper-1 immune response that activates macrophages to kill the intracellular parasite in a nitric oxide-dependent manner. Conversely, disease progression is generally associated with a T-helper-2 response that activates humoral immunity. Current control is based on chemotherapeutic treatments which are expensive, toxic and associated with high relapse and resistance rates. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-attenuated strains of Leishmania. However, to date, no vaccine is available despite substantial efforts by many laboratories. Major impediments in Leishmania vaccine development include: lack of adequate funding from national and international agencies, problems related to the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, an important but least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on the progress of the search for an effective vaccine against human and canine leishmaniasis.
authors.affiliation: Department of Tropical and Infectious Diseases, Institute of Primate Research, Karen, Nairobi 24481-00502, Kenya; ; Department of Zoological Sciences, Kenyatta University, Nairobi 43844-00100, Kenya.
authors.forename: Joshua Muli
authors.initials: JM
authors.lastname: Mutiso
authors.forename: John Chege
authors.initials: JC
authors.lastname: Macharia
authors.forename: Maria Ndunge
authors.initials: MN
authors.lastname: Kiio
authors.forename: James Maina
authors.initials: JM
authors.lastname: Ichagichu
authors.forename: Hitler
authors.initials: H
authors.lastname: Rikoi
authors.forename: Michael Muita
authors.initials: MM
authors.lastname: Gicheru
keywords: Leishmania; immune response; immunization; leishmaniasis; vaccine
references.citation: Indian J Med Res. 2006 Mar;123(3):439-54
references.pmid: 16778322
references.citation: J Infect Dis. 2003 Oct 15;188(8):1250-7
references.pmid: 14551897
references.citation: Clin Vaccine Immunol. 2008 May;15(5):836-42
references.pmid: 18353921
references.citation: Prog Clin Biol Res. 1980;47:259-85
references.pmid: 7010374
references.citation: J Immunol. 2009 Aug 1;183(3):1813-20
references.pmid: 19592661
references.citation: Trans R Soc Trop Med Hyg. 2005 Aug;99(8):593-8
references.pmid: 15893351
references.citation: Adv Parasitol. 1999;42:343-410
references.pmid: 10050276
references.citation: Int J Antimicrob Agents. 2010 Nov;36 Suppl 1:S62-5
references.pmid: 20728317
references.citation: Vaccine. 2001 May 14;19(25-26):3485-92
references.pmid: 11348715
references.citation: J Immunol. 1991 Nov 15;147(10):3575-80
references.pmid: 1940356
references.citation: J Am Vet Med Assoc. 2005 Apr 15;226(8):1316-22
references.pmid: 15844420
references.citation: Vaccine. 2006 Mar 10;24(11):1800-10
references.pmid: 16310900
references.citation: Indian J Med Res. 2006 Mar;123(3):423-38
references.pmid: 16778321
references.citation: Immunobiology. 2013 Jan;218(1):114-26
references.pmid: 22440312
references.citation: J Clin Microbiol. 2010 Jan;48(1):131-6
references.pmid: 19923480
references.citation: Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10267-71
references.pmid: 7479765
references.citation: Clin Exp Immunol. 2005 May;140(2):349-53
references.pmid: 15807861
references.citation: Infect Immun. 2004 Oct;72(10):5654-61
references.pmid: 15385463
references.citation: J Trop Med. 2012;2012:631460
references.pmid: 21912560
references.citation: Trans R Soc Trop Med Hyg. 2003 May-Jun;97(3):365-8
references.pmid: 15228261
references.citation: Vaccine. 2007 May 30;25(22):4502-9
references.pmid: 17418459
references.citation: J Infect Dis. 2002 Nov 1;186(9):1314-20
references.pmid: 12402201
references.citation: J Biomed Biotechnol. 2010;2010:181690
references.pmid: 20145701
references.citation: Clin Dermatol. 1996 Sep-Oct;14(5):503-12
references.pmid: 8889328
references.citation: Clin Dermatol. 1996 Sep-Oct;14(5):489-95
references.pmid: 8889326
references.citation: Am J Trop Med Hyg. 2001 Nov;65(5):510-7
references.pmid: 11716106
references.citation: Acta Trop. 1993 Mar;53(1):59-72
references.pmid: 8096110
references.citation: Vaccine. 2000 Dec 8;19(9-10):1082-92
references.pmid: 11137242
references.citation: Infect Immun. 2008 Mar;76(3):1003-15
references.pmid: 18195029
references.citation: Vaccine. 2009 Dec 10;28(1):53-62
references.pmid: 19818721
references.citation: Lancet Infect Dis. 2007 Sep;7(9):581-96
references.pmid: 17714672
references.citation: Vaccine. 2008 Oct 29;26(46):5888-95
references.pmid: 18786587
references.citation: Science. 1996 Oct 18;274(5286):421-3
references.pmid: 8832890
references.citation: Vaccine. 2004 Sep 28;22(29-30):4097-100
references.pmid: 15364462
references.citation: Curr Opin Immunol. 2000 Aug;12(4):442-7
references.pmid: 10899026
references.citation: Int J Dermatol. 2002 Feb;41(2):73-8
references.pmid: 11982640
references.citation: Vaccine. 2003 May 16;21(17-18):2161-8
references.pmid: 12706707
references.citation: Vaccine. 2000 Jul 1;18(26):3011-7
references.pmid: 10825604
references.citation: J Biomed Biotechnol. 2007;2007(6):90520
references.pmid: 17710244
references.citation: Hum Gene Ther. 2006 Nov;17(11):1051-61
references.pmid: 17032152
references.citation: Vaccine. 2009 May 11;27(21):2884-90
references.pmid: 19428898
references.citation: Infect Immun. 2004 Jun;72(6):3622-7
references.pmid: 15155672
references.citation: Int J Parasitol. 2004 May;34(6):655-64
references.pmid: 15111087
references.citation: Vaccine. 2008 Jan 30;26(5):623-38
references.pmid: 18180079
references.citation: Parasit Vectors. 2009 Mar 26;2 Suppl 1:S1
references.pmid: 19426440
references.citation: Vaccine. 1998 Dec;16(20):2077-84
references.pmid: 9796067
references.citation: Vaccine. 2005 Sep 23;23(40):4805-10
references.pmid: 16011864
references.citation: Med Parazitol (Mosk). 1999 Jan-Mar;(1):58-9
references.pmid: 10414052
references.citation: N Engl J Med. 1999 Jul 22;341(4):277-8
references.pmid: 10413742
references.citation: J Am Board Fam Pract. 2002 Sep-Oct;15(5):401-6
references.pmid: 12350062
references.citation: Trans R Soc Trop Med Hyg. 2008 Jan;102(1):58-63
references.pmid: 17963805
references.citation: Vaccine. 2009 Jun 2;27(27):3505-12
references.pmid: 19464528
references.citation: Southeast Asian J Trop Med Public Health. 2007 Jan;38(1):8-12
references.pmid: 17539239
references.citation: Infect Immun. 2005 Oct;73(10):6372-82
references.pmid: 16177308
references.citation: Parasitology. 1998 Mar;116 ( Pt 3):219-21
references.pmid: 9550214
references.citation: Vaccine. 2004 Jun 2;22(17-18):2234-43
references.pmid: 15149782
references.citation: J Immunol. 1988 Jun 1;140(11):3971-7
references.pmid: 3131421
references.citation: Eur J Immunol. 2008 Nov;38(11):3090-100
references.pmid: 18924210
references.citation: J Glob Infect Dis. 2010 May;2(2):135-46
references.pmid: 20606969
references.citation: Vaccine. 2009 Jul 16;27(33):4439-46
references.pmid: 19500553
references.citation: Br Med Bull. 2006 Jul 17;75-76:115-30
references.pmid: 16847165
references.citation: Braz J Med Biol Res. 1994 Feb;27(2):547-51
references.pmid: 8081280
references.citation: PLoS Pathog. 2009 May;5(5):e1000441
references.pmid: 19461875
references.citation: Mem Inst Oswaldo Cruz. 2002 Oct;97(7):1041-8
references.pmid: 12471434
references.citation: J Glob Infect Dis. 2010 May;2(2):177-85
references.pmid: 20606974
references.citation: Mol Biochem Parasitol. 1995 Nov;74(2):189-200
references.pmid: 8719160
references.citation: Vaccine. 2006 Mar 20;24(13):2423-31
references.pmid: 16386824
references.citation: Parasite Immunol. 2010 Nov-Dec;32(11-12):722-30
references.pmid: 21039612
references.citation: Euro Surveill. 2010 Mar 11;15(10):19505
references.pmid: 20403308
references.citation: Infect Immun. 1997 Jun;65(6):2371-7
references.pmid: 9169776
references.citation: Vaccine. 2004 Mar 12;22(9-10):1320-6
references.pmid: 15003662
references.citation: Hum Gene Ther. 1998 Sep 1;9(13):1899-907
references.pmid: 9741428
references.citation: Trends Parasitol. 2005 May;21(5):244-9
references.pmid: 15837614
references.citation: Infect Immun. 2001 Jan;69(1):245-51
references.pmid: 11119512
references.citation: Clin Infect Dis. 2000 May;30(5):840
references.pmid: 10816165
references.citation: Annu Rev Immunol. 1995;13:151-77
references.pmid: 7612219
references.citation: Vet Parasitol. 1995 Dec;60(3-4):199-212
references.pmid: 8747903
references.citation: Ann N Y Acad Sci. 2004 Oct;1026:267-72
references.pmid: 15604504
references.citation: PLoS One. 2011 Feb 02;6(2):e14644
references.pmid: 21311597
references.citation: J Biol Chem. 2004 Jun 11;279(24):25703-10
references.pmid: 15084606
references.citation: Vaccine. 2008 Aug 18;26(35):4585-93
references.pmid: 18588933
references.citation: Clin Microbiol Rev. 2006 Jan;19(1):111-26
references.pmid: 16418526
references.citation: Colloids Surf B Biointerfaces. 2009 Nov 1;74(1):37-44
references.pmid: 19615870
references.citation: Mol Biochem Parasitol. 1992 Jan;50(1):151-60
references.pmid: 1542309
references.citation: Trans R Soc Trop Med Hyg. 2003 Jul-Aug;97(4):469-72
references.pmid: 15259484
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7845-50
references.pmid: 18509051
references.citation: J Immunol. 1999 Oct 15;163(8):4481-8
references.pmid: 10510390
references.citation: Infect Immun. 2003 Nov;71(11):6499-509
references.pmid: 14573672
references.citation: Int J Parasitol. 2004 Jan;34(1):55-62
references.pmid: 14711590
references.citation: Vaccine. 2002 Sep 10;20(27-28):3292-303
references.pmid: 12213399
references.citation: Clin Vaccine Immunol. 2010 Apr;17(4):660-7
references.pmid: 20106998
references.citation: Science. 1995 Apr 28;268(5210):563-6
references.pmid: 7725103
references.citation: J Immunol. 2004 Apr 15;172(8):4902-6
references.pmid: 15067069
references.citation: Vaccine. 2008 Mar 25;26(14):1709-24
references.pmid: 18295939
references.citation: Immunol Cell Biol. 2007 Feb-Mar;85(2):138-47
references.pmid: 17146466
references.citation: Parasitol Res. 2007 Feb;100(3):449-54
references.pmid: 17058112
references.citation: Vaccine. 2002 Sep 10;20(27-28):3277-84
references.pmid: 12213397
references.citation: PLoS Negl Trop Dis. 2008;2(10):e313
references.pmid: 18958165
references.citation: Vaccine. 1999 Feb 5;17(5):466-72
references.pmid: 10073725
references.citation: Vaccine. 2008 Mar 17;26(12):1585-94
references.pmid: 18328956
references.citation: Vet Parasitol. 2002 Jul 2;106(4):315-24
references.pmid: 12079737
references.citation: J Immunol. 2009 Jul 1;183(1):470-9
references.pmid: 19542458
references.citation: Vaccine. 2007 Aug 10;25(32):6107-17
references.pmid: 17629372
references.citation: J Immunol. 2004 Mar 15;172(6):3793-7
references.pmid: 15004184
references.citation: Vaccine. 2005 Nov 1;23(45):5245-51
references.pmid: 16054272
references.citation: Parasit Vectors. 2011 Jul 27;4:150
references.pmid: 21794145
references.citation: Immunotechnology. 1996 Jun;2(2):77-83
references.pmid: 9373316
references.citation: Clin Dermatol. 1996 Sep-Oct;14(5):497-502
references.pmid: 8889327
references.citation: Vet Parasitol. 2006 Oct 10;141(1-2):1-8
references.pmid: 16750885
references.citation: Lancet. 1998 May 23;351(9115):1540-3
references.pmid: 10326536
references.citation: Trans R Soc Trop Med Hyg. 2000 Nov-Dec;94(6):698-703
references.pmid: 11198661
references.citation: Rev Inst Med Trop Sao Paulo. 2010 Sep-Oct;52(5):259-66
references.pmid: 21049230
references.citation: Immunity. 1997 May;6(5):541-9
references.pmid: 9175832
references.citation: Immunol Lett. 1999 Jan;65(1-2):105-8
references.pmid: 10065635
references.citation: Vaccine. 2007 Oct 16;25(42):7450-8
references.pmid: 17804125
references.citation: J Exp Med. 1997 Oct 6;186(7):1137-47
references.pmid: 9314562
references.citation: Infect Immun. 2007 Sep;75(9):4648-54
references.pmid: 17606603
references.citation: J Biomed Res. 2012 Jan;26(1):8-16
references.pmid: 23554725
references.citation: Infect Immun. 2001 Aug;69(8):4719-25
references.pmid: 11447143
references.citation: Microbes Infect. 2010 Nov;12(12-13):967-77
references.pmid: 20601076
references.citation: Vaccine. 2012 Jun 6;30(26):3957-64
references.pmid: 22465747
references.citation: Vaccine. 2006 May 8;24(19):4247-59
references.pmid: 16216395
references.citation: J Infect Dis. 1998 May;177(5):1352-7
references.pmid: 9593024
references.citation: Vaccine. 2007 Nov 14;25(46):7962-71
references.pmid: 17942199
references.citation: N Engl J Med. 1993 Nov 25;329(22):1632-8
references.pmid: 8232433
references.citation: Mol Immunol. 2009 Jan;46(3):366-74
references.pmid: 19042022
references.citation: Vaccine. 2010 Jan 8;28(3):597-603
references.pmid: 19800443
references.citation: Lancet. 1987 Feb 21;1(8530):401-5
references.pmid: 2880213
references.citation: Clin Microbiol Rev. 2001 Apr;14(2):229-43
references.pmid: 11292637
references.citation: Vaccine. 2010 Apr 26;28(19):3333-40
references.pmid: 20206667
references.citation: J Immunol. 2000 Dec 15;165(12):7064-71
references.pmid: 11120835
references.citation: Clin Vaccine Immunol. 2010 Feb;17(2):267-73
references.pmid: 20032217
references.citation: Lancet. 2000 Nov 4;356(9241):1565-9
references.pmid: 11075771