title: The development and clinical evaluation of second-generation leishmaniasis vaccines.
abstract: Infection with Leishmania parasites results in a range of clinical manifestations and outcomes. Control of Leishmania parasite transmission is extremely difficult due to the large number of vectors and potential reservoirs, and none of the current treatments are ideal. Vaccination could be an effective strategy to provide sustained control. In this review, the current global situation with regard to leishmaniasis, the immunology of Leishmania infection and various efforts to identify second generation vaccine candidates are briefly discussed. The variety of clinical trials conducted using the only current second generation vaccine approved for clinical use, LEISH-F1+MPL-SE, are described. Given that epidemiological evidence suggests that reducing the canine reservoir also positively impacts human incidence, efforts at providing a vaccine for leishmaniasis in dogs are highlighted. Finally, potential refinements and surrogate markers that could expedite the introduction of a vaccine that can limit the severity and incidence of leishmaniasis are discussed.
authors.affiliation: Infectious Disease Research Institute, 1124 Columbia St, Suite 400, Seattle, WA 98104, USA. mduthie@idri.org
authors.forename: Malcolm S
authors.initials: MS
authors.lastname: Duthie
authors.forename: Vanitha S
authors.initials: VS
authors.lastname: Raman
authors.forename: Franco M
authors.initials: FM
authors.lastname: Piazza
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004197:Disease Reservoirs; D004283:Dog Diseases / Q000517:prevention & control / Q000635:transmission; D004285:Dogs; D014943:Global Health; D006801:Humans; D015994:Incidence; D007896:Leishmaniasis / Q000453:epidemiology* / Q000517:prevention & control*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*
chemical_list: D054332:Leishmaniasis Vaccines
references.citation: Vaccine. 2005 May 25;23(28):3642-8
references.pmid: 15882524
references.citation: J Parasitol. 1995 Dec;81(6):1000-3
references.pmid: 8544037
references.citation: N Engl J Med. 2010 Feb 11;362(6):504-12
references.pmid: 20147716
references.citation: PLoS Negl Trop Dis. 2010 Sep 14;4(9):
references.pmid: 20856856
references.citation: Am J Trop Med Hyg. 1997 Aug;57(2):168-71
references.pmid: 9288810
references.citation: Vaccine. 2010 Sep 14;28(40):6581-7
references.pmid: 20688040
references.citation: Curr Protoc Immunol. 2001 May;Chapter 19:Unit 19.2
references.pmid: 18432753
references.citation: Trans R Soc Trop Med Hyg. 2005 Aug;99(8):593-8
references.pmid: 15893351
references.citation: Vaccine. 2005 Jan 11;23(8):984-95
references.pmid: 15620471
references.citation: Clin Vaccine Immunol. 2011 Jul;18(7):1118-24
references.pmid: 21632891
references.citation: Vaccine. 2011 Apr 27;29(19):3531-7
references.pmid: 21414377
references.citation: Infect Immun. 2006 Jul;74(7):3939-45
references.pmid: 16790767
references.citation: Acta Trop. 2011 May;118(2):87-96
references.pmid: 21420925
references.citation: J Immunol. 1991 Nov 15;147(10):3575-80
references.pmid: 1940356
references.citation: Clin Infect Dis. 2004 Feb 1;38(3):377-83
references.pmid: 14727208
references.citation: Clin Dermatol. 1996 Sep-Oct;14(5):503-12
references.pmid: 8889328
references.citation: PLoS Negl Trop Dis. 2010 Nov 16;4(11):e889
references.pmid: 21103373
references.citation: Clin Dermatol. 1996 Sep-Oct;14(5):489-95
references.pmid: 8889326
references.citation: Vaccine. 2000 Dec 8;19(9-10):1082-92
references.pmid: 11137242
references.citation: Infect Immun. 2001 Jun;69(6):4103-8
references.pmid: 11349082
references.citation: Vaccine. 2009 Jul 30;27(35):4747-53
references.pmid: 19540273
references.citation: Parasitology. 2008 Aug;135(9):1035-41
references.pmid: 18561868
references.citation: Exp Parasitol. 2000 Jan;94(1):33-41
references.pmid: 10631078
references.citation: J Exp Med. 1993 Jun 1;177(6):1797-802
references.pmid: 8098733
references.citation: Vaccine. 1999 Jan 21;17(3):291-300
references.pmid: 9987166
references.citation: Braz J Infect Dis. 2001 Aug;5(4):223-32
references.pmid: 11712967
references.citation: J Immunol. 1991 Jan 15;146(2):742-8
references.pmid: 1824776
references.citation: J Infect Dis. 2003 Jun 15;187(12):1959-61
references.pmid: 12792873
references.citation: J Immunol. 2010 Aug 1;185(3):1701-10
references.pmid: 20601594
references.citation: Vaccine. 2008 Oct 29;26(46):5888-95
references.pmid: 18786587
references.citation: Clin Diagn Lab Immunol. 2001 Nov;8(6):1220-4
references.pmid: 11687466
references.citation: J Health Popul Nutr. 2010 Jun;28(3):281-5
references.pmid: 20635639
references.citation: Vaccine. 2004 Sep 28;22(29-30):4097-100
references.pmid: 15364462
references.citation: Lancet Infect Dis. 2011 Apr;11(4):322-5
references.pmid: 21453873
references.citation: Acta Trop. 2001 Jan 15;78(1):11-6
references.pmid: 11164745
references.citation: Am J Trop Med Hyg. 2008 May;78(5):741-4
references.pmid: 18458307
references.citation: Vaccine. 2009 May 11;27(21):2884-90
references.pmid: 19428898
references.citation: Vaccine. 2000 Jul 1;18(26):3011-7
references.pmid: 10825604
references.citation: Clin Diagn Lab Immunol. 1998 Sep;5(5):717-20
references.pmid: 9729541
references.citation: Vaccine. 1998 Dec;16(20):2077-84
references.pmid: 9796067
references.citation: Vaccine. 2009 Nov 23;27(50):7036-45
references.pmid: 19786136
references.citation: Vaccine. 2005 Sep 23;23(40):4805-10
references.pmid: 16011864
references.citation: Parasitol Res. 2009 Sep;105(3):717-20
references.pmid: 19452168
references.citation: BMJ. 2001 Aug 25;323(7310):419-22
references.pmid: 11520836
references.citation: Trends Parasitol. 2002 Sep;18(9):399-405
references.pmid: 12377257
references.citation: Vaccine. 2010 Oct 28;28(46):7427-35
references.pmid: 20851080
references.citation: Vaccine. 2001 Oct 12;20(1-2):59-66
references.pmid: 11567746
references.citation: Vaccine. 2009 Jun 2;27(27):3505-12
references.pmid: 19464528
references.citation: Infect Immun. 1995 Sep;63(9):3559-66
references.pmid: 7642292
references.citation: Am J Trop Med Hyg. 2008 Jul;79(1):76-8
references.pmid: 18606766
references.citation: Am J Trop Med Hyg. 2000 Jan;62(1):128-31
references.pmid: 10761737
references.citation: J Immunol. 2001 Feb 1;166(3):1912-20
references.pmid: 11160239
references.citation: Trends Immunol. 2009 Jan;30(1):23-32
references.pmid: 19059004
references.citation: Trans R Soc Trop Med Hyg. 1994 Sep-Oct;88(5):543-5
references.pmid: 7992333
references.citation: Vet Dermatol. 2005 Aug;16(4):213-32
references.pmid: 16101793
references.citation: Lancet. 1998 Feb 21;351(9102):563-5
references.pmid: 9492776
references.citation: J Infect Dis. 2006 Oct 15;194(8):1151-9
references.pmid: 16991091
references.citation: Vet Immunol Immunopathol. 2010 Jun 15;135(3-4):296-302
references.pmid: 20132994
references.citation: Rev Soc Bras Med Trop. 2006 Jan-Feb;39(1):14-21
references.pmid: 16501760
references.citation: Mol Biochem Parasitol. 1992 Jan;50(1):151-60
references.pmid: 1542309
references.citation: Infect Immun. 1995 Nov;63(11):4261-7
references.pmid: 7591056
references.citation: Vaccine. 2002 Sep 10;20(27-28):3292-303
references.pmid: 12213399
references.citation: Immunol Rev. 1989 Dec;112:161-82
references.pmid: 2575073
references.citation: Trans R Soc Trop Med Hyg. 2000 Sep-Oct;94(5):484-7
references.pmid: 11132371
references.citation: Science. 1995 Apr 28;268(5210):563-6
references.pmid: 7725103
references.citation: Vaccine. 2006 Nov 17;24(47-48):6944-54
references.pmid: 17049693
references.citation: Nat Med. 2007 Jul;13(7):843-50
references.pmid: 17558415
references.citation: Vaccine. 2002 Sep 10;20(27-28):3277-84
references.pmid: 12213397
references.citation: J Immunol. 2005 Jun 1;174(11):7160-71
references.pmid: 15905560
references.citation: Vaccine. 1999 Feb 5;17(5):466-72
references.pmid: 10073725
references.citation: J Immunol. 1998 Apr 15;160(8):3949-57
references.pmid: 9558102
references.citation: Vaccine. 2008 Mar 17;26(12):1585-94
references.pmid: 18328956
references.citation: J Immunol. 2009 Jul 1;183(1):470-9
references.pmid: 19542458
references.citation: J Exp Med. 1993 May 1;177(5):1505-9
references.pmid: 8097524
references.citation: Vaccine. 2005 Nov 1;23(45):5245-51
references.pmid: 16054272
references.citation: Vaccine. 2009 Dec 11;28(2):329-37
references.pmid: 19879995
references.citation: Vaccine. 2005 May 25;23(28):3716-25
references.pmid: 15882533
references.citation: Lancet. 1998 May 23;351(9115):1540-3
references.pmid: 10326536
references.citation: Expert Rev Vaccines. 2011 Apr;10(4):471-86
references.pmid: 21506645
references.citation: Infect Immun. 2001 Aug;69(8):4719-25
references.pmid: 11447143
references.citation: Vaccine. 2007 Oct 16;25(42):7450-8
references.pmid: 17804125
references.citation: Infect Immun. 2007 Sep;75(9):4648-54
references.pmid: 17606603
references.citation: J Infect Dis. 1998 May;177(5):1352-7
references.pmid: 9593024
references.citation: Trans R Soc Trop Med Hyg. 1995 Jul-Aug;89(4):390-3
references.pmid: 7570874
references.citation: J Infect Dis. 2005 Jun 15;191(12):2130-7
references.pmid: 15898000
references.citation: Infect Immun. 2005 Feb;73(2):812-9
references.pmid: 15664920
references.citation: Infect Immun. 2003 Nov;71(11):6562-72
references.pmid: 14573678
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: Vaccine. 2006 Mar 15;24(12):2169-75
references.pmid: 16325969
references.citation: Vaccine. 2010 Apr 26;28(19):3333-40
references.pmid: 20206667
references.citation: Immunol Rev. 2011 Jan;239(1):178-96
references.pmid: 21198672
references.citation: Am J Trop Med Hyg. 2002 Feb;66(2):143-6
references.pmid: 12135284
references.citation: J Immunol. 2000 Dec 15;165(12):7064-71
references.pmid: 11120835
references.citation: Lancet. 2000 Nov 4;356(9241):1565-9
references.pmid: 11075771