Development of a Leishmaniasis vaccine: The importance of MPL

Expert Review of Vaccines

Volumn 2, Issue 2, 2003, Pages 239-252

  Reed, Steven G ^a   Coler, Rhea N ^b   Campos Neto, Antonio ^b  

^a GLAXOSMITHKLINE   (United States)

^b INFECTIOUS DISEASE RESEARCH INSTITUTE   (United States)

Author keywords

Adjuvant; Antigen; Leishmania; Leishmaniasis; Monophosphoryl lipid a; MPL; Parasite; Therapeutic; Toll like receptors; Vaccine

Indexed keywords

ANTIGEN; LEISH 111F VACCINE; LEISHMANIA VACCINE; PHOSPHORYL LIPID A; SQUALENE; UNCLASSIFIED DRUG; VACCINE;

ANTIGEN PRESENTATION; DISEASE COURSE; DISEASE PREDISPOSITION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG FORMULATION; DRUG SAFETY; HELPER CELL; HUMAN; IMMUNIZATION; LEISHMANIA; LEISHMANIASIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TUBERCULOSIS;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; ANTIGENS, PROTOZOAN; HUMANS; LEISHMANIA; LEISHMANIASIS; LIPID A; MICE; PROTOZOAN VACCINES; T-LYMPHOCYTES;

EID: 0037992584     PISSN: 14760584     EISSN: None     Source Type: Journal    
DOI: 10.1586/14760584.2.2.239     Document Type: Review

References (178)

1. Grevelink SA, Lerner EA. Leishmaniasis. J. Am. Acad. Dermatol. 34, 257-272 (1996).
2. Baily GG, Nandy A. Visceral leishmaniasis: more prevalent and more problematic. J. Infect. 29, 241-247 (1994).
3. Herwaldt BL. Leishmaniasis. Lancet 354, 1191-1199 (1999).
4. Marsden PD. Mucocutaneous leishmaniasis. Br. Med. J. 301, 656-657 (1990).
5. Marsden, PD Mucosal leishmaniasis ('espundia' Escomel, 1911). Trans. R. Soc. Trop. Med. Hyg. 80, 859-876 (1986).
6. Marsden PD, Sampaio RN, Rocha R, Radke M. Mucocutaneous leishmaniasis - an unsolved clinical problem. Trop. Doct. 7, 7-11 (1977).
7. Ramesh V, Mukherjee A. Post-kala-azar dermal leishmaniasis. Int. J. Dermatol. 34, 85-91 (1995).
8. Khan HM. Post-Kala-azar dermal leishmaniasis (a review of 10 cases). Bangladesh Med. Res. Counc. Bull. 3, 130-136 (1977).
9. Marsden P, Jones TC. Clinical manifestations, diagnosis and treatment of leishmaniasis. In: Leishmaniasis. Chang KP, Bray RS (Eds). Elsevier Science, Amsterdam, The Netherlands, 183-198 (1985).
10. Marsden PD. Selective primary healthcare: strategies for control of disease in the developing world. XIV. Leishmaniasis. Rev. Infect. Dis. 6, 736-744 (1984).
11. Sacks DL, Kenney RT, Kreutzer RD et al. Indian kala-azar caused by Leishmania tropica. Lancet 345, 959-961 (1995).
12. TDR News. 37, 1-2. The World Health Organization (1991).
13. Hyams KC, Riddle J, Trump DH, Graham JT. Endemic infectious diseases and biological warfare during the Gulf War: a decade of analysis and final concerns. Am. J. Trop. Med. Hyg. 65, 664-670 (2001).
14. Wolday D, Berhe N, Akuffo H, Desjeux P, Britton S. Emerging Leishmania/HIV co-infection in Africa. Med. Microbiol. Immunol. (Berl) 190, 65-67 (2001).
15. Desjeux P. Global control and Leishmania HIV co-infection. Clin. Dermatol. 17, 317-325 (1999).
16. Launois P, Louis JA, Milon G. The fate and persistence of Leishmania major in mice of different genetic backgrounds: an example of exploitation of the immune system by intracellular parasites. Parasitology 115(Suppl.), S25-S32 (1997).
17. Bogdan C, Rollinghoff M. The immune response to Leishmania: mechanisms of parasite control and evasion. Int. J. Parasitol. 28, 121-134 (1998).
18. Aebischer T, Moody SF, Handman E. Persistence of virulent Leishmania major in murine cutaneous leishmaniasis: a possible hazard for the host. Infect. Immun. 61, 220-226 (1993).
19. Marsden PD, Llanos-Cuentas EA, Lago E et al. Human mucocutaneous leishmaniasis in Tres Bracos, Bahia-Brazil. An area of Leishmania braziliensis transmission. III. Mucosal disease: presentation and initial evolution. Rev. Soc. Bras. Med. Trop. 17, 179-186 (1984).
20. Ashford RW. The leishmaniases as model zoonoses. Ann. Trop. Med. Parasitol. 91, 693-701 (1997).
21. Lainson R. The American leishmaniases: some observations on their ecology and epidemiology Trans. R. Soc. Trop. Med. Hyg. 77, 569-596 (1983).
22. Ambroise-Thomas P. Parasitic diseases and immunodeficiencies. Parasitology 122(Suppl.), S65-S71 (2001).
23. Albrecht H. Leishmaniosis - new perspectives on an underappreciated opportunistic infection. AIDS 12, 2225-2226 (1998).
24. Abath FG, Montenegro SM, Gomes YM. Vaccines against human parasitic diseases: an overview. Acta Trop. 71, 237-254 (1998).
25. Cox FE. Designer vaccines for parasitic diseases. Int. J. Parasitol. 27, 1147-1157 (1997).
26. Higashi GI. Vaccines for parasitic diseases. Ann. Rev. Public Health 9, 483-501 (1988).
27. Hommel M, Jaffe CL, Travi B, Milon G. Experimental models for leishmaniasis and for testing antileishmanial vaccines. Ann. Trop. Med. Parasitol. 89(Suppl. 1), 55-73 (1995).
28. Jaffe CL. Recent trends in vaccine development and immunization. Clin. Dermatol. 17, 339-344 (1999).
29. Modabber F. Experiences with vaccines against cutaneous leishmaniasis: of men and mice. Parasitology 98(Suppl), S49-S60 (1989).
30. Modabber F. Development of vaccines against leishmaniasis. Scand. J. Infect. Dis. Suppl. 76, 72-78 (1990).
31. Modabber F. Vaccines against leishmaniasis. Ann. Trop. Med. Parasitol. 89(Suppl. 1), 83-88 (1995).
32. Modabber F. First generation leishmaniasis vaccines in clinical development: moving but what next? Curr. Opin. Anti-infect. Investig. Drugs 2, 35-39 (2000).
33. Jones DE, Elloso MM, Scott P. Host susceptibility factors to cutaneous leishmaniasis. Front. Biosci. 3, D1171-D1180 (1998).
34. Reiner SL, Locksley RM. The regulation of immunity to Leishmania major. Ann. Rev. Immunol. 13, 151-177 (1995).
35. Reed SG, Scott P. T-cell and cytokine responses in leishmaniasis. Curr. Opin. Immunol. 5, 524-531 (1993).
36. Russo DM, Barral-Netto M, Barral A, Reed SG. Human T-cell responses in Leishmania infections. Prog. Clin. Parasitol. 3, 119-144 (1993).
37. Liew FY, O'Donnell CA. Immunology of leishmaniasis. Adv. Parasitol. 32, 161-259 (1993).
38. Locksley RM, Louis JA. Immunology of leishmaniasis. Curr. Opin. Immunol. 4, 413-418 (1992).
39. + T-cell subsets in the regulation of parasite immunity and disease. Immunol. Rev. 112, 161-182 (1989).
40. Liew FY. Regulation of cell-mediated immunity in leishmaniasis. Curr. Top. Microbiol. Immunol. 155, 53-64 (1990).
41. Lohoff M, Gessner A, Bogdan C, Rollinghoff M. The Th1/Th2 paradigm and experimental murine leishmaniasis. Int. Arch. Allergy Immunol. 115, 191-202 (1998)
42. + T-cells in pathogenesis associated with Leishmania amazonensis infection. J. Immunol. 158, 5374-5383 (1997).
43. + T-cells are not essential for T-helper cell 2 immune responses. J. Exp. Med. 184, 1295-1304 (1996).
44. + T-cells do not mediate a protective immune response. Immunobiology 195, 243-260 (1996).
45. Erb KJ, Blank C, Moll H. Susceptibility to Leishmania major in IL-4 transgenic mice is not correlated with the lack of a Th1 immune response. Immunol. Cell Biol. 74, 239-244 (1996).
46. Chakkalath HR, Theodos CM, Markowitz JS, Grusby MJ, Glimcher LH, Titus RG. Class II major histocompatibility complex-deficient mice initially control an infection with Leishmania major but succumb to the disease. J. Infect. Dis. 171, 1302-1308 (1995).
47. Locksley RM, Wakil AE, Corry DB, Pingel S, Bix M, Fowell DJ. The development of effector T-cell subsets in murine Leishmania major infection. Ciba Found. Symp. 195, 110-117 (1995).
48. 2-microglobulin-deficient mice fail to confirm a primary protective role for CD8 cells in experimental leishmaniasis. J. Immunol. 151, 2077-2086 (1993).
49. 2-microglobulin-deficient mice. Immunol. Lett. 37, 13-17 (1993).
50. Reiner SL, Seder RA. T-helper cell differentiation in immune response. Curr. Opin. Immunol. 7, 360-366 (1995).
51. + T-cells in resistant mice upon infection with Leishmania major. Immunity 13, 771-782 (2000).
52. + subsets in leishmaniasis. J. Cell Biochem. 53, 323-328 (1993).
53. Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM. Reciprocal expression of interferon-γ or interleukin-4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T-cell subsets. J. Exp. Med. 169, 59-72 (1989).
54. Hsieh CS, Macatonia SE, O'Garra A, Murphy KM. T-cell genetic background determines default T-helper phenotype development in vitro. J. Exp. Med. 181, 713-721 (1995).
55. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T-cell done. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348-2357 (1986).
56. Muller I, Pedrazzini T, Farrell JP, Louis J. T-cell responses and immunity to experimental infection with Leishmania major. Ann. Rev. Immunol. 7, 561-578 (1989).
57. Noben-Trauth N, Kropf P, Muller I. Susceptibility to Leishmania major infection in interleukin-4-deficient mice. Science 271, 987-990 (1996).
58. + T-cell subsets in experimental cutaneous leishmaniasis. Mem. Inst. Oswaldo Cruz 83(Suppl. 1), 256-259 (1988).
59. Scott P, Natovitz P, Coffman RL, Pearce E, Sher A. Immunoregulation of cutaneous leishmaniasis. T-cell lines that transfer protective immunity or exacerbation belong to different T-helper subsets and respond to distinct parasite antigens. J. Exp. Med 168, 1675-1684 (1988).
60. Solbach W, Laskay T. The host response to Leishmania infection. Adv. Immunol. 74, 275-317 (2000).
61. Blackwell JM. Leishmaniasis epidemiology: all down to the DNA. Parasitology 104(Suppl), S19-S34 (1992).
62. Blackwell JM, Roach TI, Atkinson SE, Ajioka JW, Barton CH, Shaw MA. Genetic regulation of macrophage priming/activation: the Lsh gene story. Immunol. Lett. 30, 241-248 (1991).
63. Blackwell JM. Genetic susceptibility to leishmanial infections: studies in mice and man. Parasitology 112(Suppl.), S67-S74 (1996).
64. Kaye PM, Roberts MB, Blackwell JM. Analysing the immune response to L. donovani infection. Ann. Inst. Pasteur Immunol. 138, 762-768 (1987).
65. Kaye PM, Curry AJ, Bancroft GJ, Lang T. Antigen processing and presentation: modelling with Leishmania. Behring Inst. Mitt. 13-19 (1991).
66. McLeod R, Buschman E, Arbuckle LD, Skamene E. Immunogenetics in the analysis of resistance to intracellular pathogens. Curr. Opin. Immunol. 7, 539-552 (1995).
67. Mock B, Blackwell J, Hilgers J, Potter M, Nacy C. Genetic control of Leishmania major infection in congenic, recombinant inbred and F2 populations of mice. Eur. J. Immunogenet. 20, 335-348 (1993).
68. Wassom DL, Kelly EA. The role of the major histocompatibility complex in resistance to parasite infections. Crit. Rev. Immunol. 10, 31-52 (1990).
69. Launois P, Himmelrich H, Tacchini-Cottier F, Milon G, Louis JA. New insight into the mechanisms underlying Th2 cell development and susceptibility to Leishmania major in BALB/c mice. Microbes Infect. 1, 59-64 (1999).
70. Gorczynski RM. Nature of resistance to leishmaniasis in experimental rodents. Dev. Comp. Immunol. 6, 199-207 (1982).
71. Guler ML, Gorham JD, Hsieh CS et al. Genetic susceptibility to Leishmania: IL-12 responsiveness in Th1 cell development. Science 271, 984-987 (1996).
72. Scharton-Kersten T, Afonso LC, Wysocka M, Trinchieri G, Scott P. IL-12 is required for natural killer cell activation and subsequent T-helper 1 cell development in experimental leishmaniasis. J. Immunol. 154, 5320-5330 (1995).
73. Scott P, Scharton T. Interaction between the innate and the acquired immune system following infection of different mouse strains with Leishmania major. Ann. NY Acad. Sci. 730, 84-92 (1994).
74. Scott P. Th cell development and regulation in experimental cutaneous leishmaniasis. Chem. Immunol. 63, 98-114 (1996).
75. Locksley RM, Reiner SL, Hatam F, Littman DR, Killeen N. Helper T-cells without CD4: control of leishmaniasis in CD4-deficient mice. Science 261, 1448-1451 (1993).
76. Sacks DL, Scott PA, Asofsky R, Sher FA. Cutaneous leishmaniasis in antiIgM-treated mice: enhanced resistance due to functional depletion of a B-cell-dependent T-cell involved in the suppressor pathway. J. Immunol. 132, 2072-2077 (1984).
77. + B-cells has no effect on the course of Leishmania major infection in susceptible and resistant mice. Clin. Exp. Immunol. 117, 123-129 (1999).
78. Bretscher PA, Wei G, Menon JN, Bielefeldt-Ohmann H. Establishment of stable, cell-mediated immunity that makes 'susceptible' mice resistant to Leishmania major. Science 257, 539-542 (1992).
79. Smelt SC, Cotterell SE, Engwerda CR, Kaye PM. B-cell-deficient mice are highly resistant to Leishmania donovani infection but develop neutrophil-mediated tissue pathology. J. Immunol. 164, 3681-3688 (2000).
80. Akuffo H, Maasho K, Blostedt M, Hojeberg B, Britton S, Bakhiet M. Leishmania aethiopica derived from diffuse leishmaniasis patients preferentially induce mRNA for interleukin-10 while those from localized leishmaniasis patients induce interferon-γ. J. Infect. Dis. 175, 737-741 (1997).
81. Kemp K. Cytokine-producing T-cell subsets in human leishmaniasis. Arch. Immunol. Ther. Exp. (Warsz.) 48, 173-176 (2000).
82. Pirmez C, Yamamura M, Uyemura K, Paes-Oliveira M, Conceicao-Silva F, Modlin RL. Cytokine patterns in the pathogenesis of human leishmaniasis. J. Clin. Invest. 91, 1390-1395 (1993).
83. Caceres-Dittmar G, Tapia FJ, Sanchez MA et al. Determination of the cytokine profile in American cutaneous leishmaniasis using the polymerase chain reaction. Clin. Exp. Immunol. 91, 500-505 (1993).
84. Kharazmi A, Kemp K, Ismail A et al. T-cell response in human leishmaniasis. Immunol. Lett. 65, 105-108 (1999).
85. Kenney RT, Sacks DL, Gam AA, Murray HW, Sundar S. Splenic cytokine responses in Indian kala-azar before and after treatment. J. Infect. Dis. 177, 815-818 (1998).
86. Karp CL, El Safi SL, Wynn TA et al. In vivo cytokine profiles in patients with kala-azar. Marked elevation of both interleukin-10 and interferon-γ. J. Clin. Invest. 91, 1644-1648 (1993).
87. + T-cells in endogenous interleukin-10 secretion associated with visceral leishmaniasis. Mem. Inst. Oswaldo Cruz 95, 217-220 (2000).
88. Ghalib HW, Piuvezam MR, Skeiky YA et al. Interleukin-10 production correlates with pathology in human Leishmania donovani infections. J. Clin. Invest. 92, 324-329 (1993).
89. Antunes CM, Mayrink W, Magalhaes PA et al. Controlled field trials of a vaccine against New World cutaneous leishmaniasis. Int. J. Epidemiol. 15, 572-580 (1986).
90. Armijos RX, Weigel MM, Aviles H, Maldonado R, Racines J. Field trial of a vaccine against New World cutaneous leishmaniasis in an at-risk child population: safety, immunogenicity and efficacy during the first 12 months of follow-up. J. Infect. Dis. 177, 1352-1357 (1998).
91. Genaro O, de Toledo VP, da Costa CA, Hermeto MV, Afonso LC, Mayrink W. Vaccine for prophylaxis and immunotherapy, Brazil. Clin. Dermatol. 14, 503-512 (1996).
92. Green MS, Kark JD, Witztum E, Greenblatt CL, Spira DT. Frozen stored Leishmania tropica vaccine: the effects of dose, route of administration and storage on the evolution of the clinical lesion. Two field trials in the Israel Defense Forces. Trans R. Soc. Trop. Med. Hyg. 77, 152-159 (1983).
93. Gunders AE, Naggan L, Michaeli D. Follow-up study of a vaccination programme against cutaneous leishmaniasis. I. Vaccination with a 5 year-old human strain of L. tropica from the Negev. Trans. R. Soc. Trop. Med. Hyg. 66, 235-238 (1972).
94. Khalil EA, El Hassan AM, Zijlstra EE et al. Autoclaved Leishmania major vaccine for prevention of visceral leishmaniasis: a randomised, double-blind, BCG-controlled trial in Sudan. Lancet 356, 1565-1569 (2000).
95. Marzochi KB, Marzochi MA, Silva AF et al. Phase 1 study of an inactivated vaccine against American tegumentary leishmaniasis in normal volunteers in Brazil. Mem. Inst. Oswaldo Cruz 93, 205-212 (1998).
96. Mayrink W, Antunes CM, da Costa CA et al. Further trials of a vaccine against American cutaneous leishmaniasis. Trans R. Soc. Trop. Med. Hyg. 80, 1001 (1986).
97. Nadim A, Javadian E, Tahvildar-Bidruni G, Ghorbani M. Effectiveness of leishmanization in the control of cutaneous leishmaniasis. Bull. Soc. Pathol. Exot. Filiales 76, 377-383 (1983).
98. Sharifi I, FeKri AR, Aflatonian MR et al. Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran. Lancet 351, 1540-1543 (1998).
99. Palanova L, Volf P. Carbohydrate-binding specificities and physicochemical properties of lectins in various tissue of phlebotominae sandflies. Folia Parasitol. (Praha) 44, 71-76 (1997).
100. Sacks DL, Pimenta PF, McConville MJ, Schneider P, Turco SJ. Stage-specific binding of Leishmania donovani to the sand fly vector midgut is regulated by conformational changes in the abundant surface lipophosphoglycan. J. Exp. Med. 181, 685-697 (1995).
101. Saraiva EM, Pimenta PF, Brodin TN, Rowton E, Modi GB, Sacks DL. Changes in lipophosphoglycan and gene expression associated with the development of Leishmania major in Phlebotomus papatasi. Parasitology 111(Pt 3), 275-287 (1995).
102. Volf P, Kiewegova A, Svobodova M. Sandfly midgut lectin: effect of galactosamine on Leishmania major infections. Med. Vet. Entomol. 12, 151-154 (1998).
103. Tonui WK. Leishmania transmission-blocking vaccines: a review. East Afr. Med. J. 76, 93-96 (1999).
104. Valenzuela JG, Belkaid Y, Garfield MK et al. Toward a defined antileishmania vaccine targeting vector antigens. Characterization of a protective salivary protein. J. Exp. Med. 194, 331-342 (2001).
105. Donnelly KB, Lima HC, Titus RG. Histologic characterization of experimental cutaneous leishmaniasis in mice infected with Leishmania braziliensis in the presence or absence of sand fly vector salivary gland lysate. J. Parasitol. 84, 97-103 (1998).
106. Titus RG, Ribeiro JM. Salivary gland lysates from the sand fly Lutzomyia longipalpis enhance Leishmania infectivity. Science 239, 1306-1308 (1988).
107. Tonui WK, Mbati PA, Anjili CO et al. Transmission blocking vaccine studies in leishmaniasis: II. Effect of immunisation using Leishmania major derived 63 kilodalton glycoprotein, lipophosphoglycan and whole parasite antigens on the course of L. major infection in BALB/c mice. East Afr. Med J. 78, 90-92 (2001).
108. Aebischer T, Wolfram M, Patzer SI, Ilg T, Wiese M, Overath P. Subunit vaccination of mice against New World cutaneous leishmaniasis: comparison of three proteins expressed in amastigotes and six adjuvants. Infect. Immun. 68, 1328-1336 (2000).
109. Campos-Neto A, Porrozzi R, Greeson K et al. Protection against cutaneous leishmaniasis induced by recombinant antigens in murine and nonhuman primate models of the human disease. Infect. Immun. 69, 4103-4108 (2001).
110. Colmenares M, Tiemeyer M, Kima P, McMahon-Pratt D. Biochemical and biological characterization of the protective Leishmania pifanoi amastigote antigen P-8. Infect. Immun. 69, 6776-6784 (2001).
111. Connell ND, Medina-Acosta E, McMaster WR, Bloom BR, Russell DG. Effective immunization against cutaneous leishmaniasis with recombinant bacille Calmette-Guerin expressing the Leishmania surface proteinase gp63. Proc. Natl Acad Sci. USA 90, 11473-11477 (1993).
112. Dole VS, Raj VS, Ghosh A, Madhubala R, Myler PJ, Stuart KD. Immunization with recombinant LD1 antigens protects against experimental leishmaniasis. Vaccine 19, 423-430 (2000).
113. Ghosh A, Zhang WW, Matlashewski G. Immunization with A2 protein results in a mixed Th1/Th2 and a humoral response which protects mice against Leishmania donovani infections. Vaccine 20, 59-66 (2001).
114. Gurunathan S, Sacks DL, Brown DR et al. Vaccination with DNA encoding the immunodominant LACK parasite antigen confers protective immunity to mice infected with Leishmania major. J. Exp. Med. 186, 1137-1147 (1997).
115. Handman E, Symons FM, Baldwin TM, Curtis JM, Scheerlinck JP. 1995. Protective vaccination with promastigote surface antigen 2 from Leishmania major is mediated by a Th1 type of immune response. Infect. Immun. 63, 4261-4267.
116. Kenney RT, Sacks DL, Sypek JP, Vilela L, Gam AA, Evans-Davis K. Protective immunity using recombinant human IL-12 and alum as adjuvants in a primate model of cutaneous leishmaniasis. J. Immunol. 163, 4481-4488 (1999).
117. Lohman KL, Langer PJ, McMahon-Pratt D. Molecular cloning and characterization of the immunologically protective surface glycoprotein GP46/M-2 of Leishmania amazonensis. Proc. Natl Acad. Sci. USA 87, 8393-8397 (1990).
118. McMahon-Pratt D, Rodriguez D, Rodriguez JR, et al. Recombinant vaccinia viruses expressing GP46/M-2 protect against Leishmania infection. Infect. Immun. 61, 3351-3359 (1993).
119. Melby PC, Ogden GB, Flores HA et al. Identification of vaccine candidates for experimental visceral leishmaniasis by immunization with sequential fractions of a cDNA expression library. Infect. Immun. 68, 5595-5602 (2000).
120. Melby PC, Yang J, Zhao W, Perez LE, Cheng J. Leishmania donovani p36(LACK) DNA vaccine is highly immunogenic but not protective against experimental visceral leishmaniasis. Infect. Immun. 69, 4719-4725 (2001).
121. Mora AM, Mayrink W, Costa RT, Costa CA, Genaro O, Nascimento E. Protection of C57BL/10 mice by vaccination with association of purified proteins from Leishmania (Leishmania) amazonensis. Rev. Inst. Med. Trop. Sao Paulo 41, 243-248 (1999).
122. Mougneau W, Altare F, Wakil AE et al. Expression cloning of a protective Leishmania antigen. Science 268, 563-566 (1995).
123. Olobo JO, Anjili CO, Gicheru MM et al. Vaccination of vervet monkeys against cutaneous leishmaniosis using recombinant Leishmania 'major surface glycoprotein' (gp63). Vet. Parasitol. 60, 199-212 (1995).
124. Rafati S, Salmanian AH, Taheri T, Vafa M, Fasel N. A protective cocktail vaccine against murine cutaneous leishmaniasis with DNA encoding cysteine proteinases of Leishmania major. Vaccine 19, 3369-3375 (2001).
125. Rivier D, Bovay P, Shah R, Didisheim S, Mauel J. Vaccination against Leishmania major in a CBA mouse model of infection: role of adjuvants and mechanism of protection. Parasite Immunol. 21, 461-473 (1999).
126. Russell DG, Alexander J. Effective immunization against cutaneous leishmaniasis with defined membrane antigens reconstituted into liposomes. J. Immunol. 140, 1274-1279 (1988) (Published erratum appears in J. Immunol. 140(8), 2858 [1988]).
127. Skeiky YA, Kennedy M, Kaufman D et al. LeIF: a recombinant Leishmania protein that induces an IL-12-mediated Th1 cytokine profile. J. Immunol. 161, 6171-6179 (1998).
128. Solioz N, Blum-Tirouvanziam U, Jacquet R et al. The protective capacities of histone H1 against experimental murine cutaneous leishmaniasis. Vaccine 18, 850-859 (1999).
129. Soong L, Duboise SM, Kima P, McMahon-Pratt D. Leishmania pifanoi amastigote antigens protect mice against cutaneous leishmaniasis. Infect. Immun. 63, 3559-3566 (1995).
130. Spitzer N, Jardim A, Lippert D, Olafson RW. Long-term protection of mice against Leishmania major with a synthetic peptide vaccine. Vaccine 17, 1298-1300 (1999).
131. Stager S, Smith DF, Kaye PM. Immunization with a recombinant stage-regulated surface protein from Leishmania donovani induces protection against visceral leishmaniasis. J. Immunol. 165, 7064-7071 (2000).
132. Walker PS, Scharton-Kersten T, Rowton ED et al. Genetic immunization with glycoprotein 63 cDNA results in a helper T-cell Type 1 immune response and protection in a murine model of leishmaniasis. Hum. Gene Ther. 9, 1899-1907 (1998).
133. Webb JR, Kaufmann D, Campos-Neto A, Reed SG. Molecular cloning of a novel protein antigen of Leishmania major that elicits a potent immune response in experimental murine leishmaniasis. J. Immunol. 157, 5034-5041 (1996).
134. Webb JR, Campos-Neto A, Skeiky YA, Reed SG. Molecular characterization of the heat-inducible LmSTI1 protein of Leishmania major. Mol. Biochem. Parasitol. 89, 179-193 (1997).
135. Webb JR, Campos-Neto A, Ovendale PJ et al. Human and murine immune responses to a novel Leishmania major recombinant protein encoded by members of a multicopy gene family. Infect. Immun. 66, 3279-3289 (1998).
136. Xu D, Liew FY. Protection against leishmaniasis by injection of DNA encoding a major surface glycoprotein, gp63, of L. major. Immunology 84, 173-176 (1995).
137. Afonso LC, Scharton TM, Vieira LQ, Wysocka M, Trinchieri G, Scott P. The adjuvant effect of interleukin-12 in a vaccine against Leishmania major. Science 263, 235-237 (1994).
138. Miller MA, Skeen MJ, Ziegler HK. Protective immunity to Listeria monocytogenes elicited by immunization with heat-killed Listeria and IL-12. Potential mechanism of IL-12 adjuvanticity. Ann. NY Acad. Sci. 797, 207-227 (1996).
139. Romani L, Puccetti P, Bistoni F. Interleukin-12 in infectious diseases. Clin. Microbiol. Rev. 10, 611-636 (1997).
140. Trinchieri G. Function and clinical use of interleukin-12. Curr. Opin. Hematol. 4, 59-66 (1997).
141. Wynn TA, Cheever AW, Jankovic D et al. An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection. Nature 376, 594-596 (1995).
142. Melby PC. Vaccination against cutaneous leishmaniasis: current status. Am. J Clin. Dermatol. 3, 557-570 (2002).
143. Gonzalo RM, Del Real G, Rodriguez JR et al. 2002. A heterologous prime-boost regime using DNA and recombinant vaccinia virus expressing the Leishmania infantum P36/LACK antigen protects BALB/c mice from cutaneous leishmaniasis. Vaccine 20, 1226-1231.
144. Cruz A, Coburn CM, Beverley SM. Double targeted gene replacement for creating null mutants. Proc. Natl Acad. Sci. USA 88, 7170-7174 (1991).
145. Campos-Neto A, Webb JR, Greeson K, Coler RN, Skeiky YA, Reed SG. Vaccination with plasmid DNA encoding TSA/LmSTI1 leishmanial fusion proteins confers protection against Leishmania major infection in susceptible BALB/c mice. Infect. Immun. 70(6), 2828-2836 (2002).
146. Gurunathan S, Prussin C, Sacks DL, Seder RA. Vaccine requirements for sustained cellular immunity to an intracellular parasitic infection. Nat. Med. 4, 1409-1415 (1998).
147. Gurunathan S, Klinman DM, Seder RA. DNA vaccines: immunology, application and optimization*. Ann. Reu Immunol. 18, 927-974 (2000).
148. Gurunathan S, Wu CY, Freidag BL, Seder RA. DNA vaccines: a key for inducing long-term cellular immunity. Curr. Opin. Immunol. 12, 442-447 (2000).
149. + T-cells. J. Immunol. 165, 915-924 (2000).
150. Mendez S, Gurunathan S, Kamhawi S et al. The potency and durability of DNA- and protein-based vaccines against Leishmania major evaluated using low-dose, intradermal challenge. J. Immunol. 166, 5122-5128 (2001).
151. Stacey KJ, Blackwell JM. Immunostimulatory DNA as an adjuvant in vaccination against Leishmania major. Infect. Immun. 67, 3719-3726 (1999).
152. Walker PS, Scharton-Kersten T, Krieg AM et al. Immunostimulatory oligodeoxynucleotides promote protective immunity and provide systemic therapy for leishmaniasis via IL-12- and IFN-γdependent mechanisms. Proc. Natl Acad. Sci. USA 96, 6970-6975 (1999).
153. Zimmermann S, Egeter O, Hausmann S et al. CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis. J. Immunol. 160, 3627-3630 (1998).
154. Borges MM, Campos-Neto A, Sleath P et al. Potent stimulation of the innate immune system by a Leishmania brasiliensis recombinant protein. Infect. Immun. 69, 5270-5277 (2001).
155. Probst P, Skeiky YA, Steeves M, Gervassi A, Grabstein KH, Reed SG. A Leishmania protein that modulates interleukin (IL)-12, IL-10 and tumor necrosis factor-α production and expression of B7-1 in human monocytederived antigen-presenting cells. Eur. J. Immunol. 27, 2634-2642 (1997).
156. Skeiky YA, Guderian JA, Benson DR et al. A recombinant Leishmania antigen that stimulates human peripheral blood mononuclear cells to express a Th1-type cytokine profile and to produce interleukin-12. J. Exp. Med. 181, 1527-1537 (1995).
157. Amaral VF, Ransatto VA, Conceicao-Silva F et al. Leishmania amazonensis: the Asian rhesus macaques (Macaca mulatta) as an experimental model for study of cutaneous leishmaniasis. Exp. Parasitol. 82, 34-44 (1996).
158. Walsh GP, Tan EV, Dela Cruz EC et al. The Philippine cynomolgus monkey (Macaca fasicularis) provides a new nonhuman primate model of tuberculosis that resembles human disease. Nat. Med. 2, 430-436 (1996).
159. Gormus BJ, Baskin GB, Xu K et al. Antileprosy protective vaccination of rhesus monkeys with BCG or BCG plus heatkilled Mycobacterium leprae: immunologic observations. Int. J. Lepr. Other Mycobact. Dis. 68, 27-39 (2000).
160. Gormus BJ, Baskin GB, Xu K et al. Protective immunization of monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: clinical results. Lepr. Rev. 69, 6-23 (1998).
161. Githure JI, Reid GD, Binhazim AA, Anjili CO, Shatry AM, Hendricks LD. Leishmania major, the suitability of East African nonhuman primates as animal models for cutaneous leishmaniasis. Exp. Parasitol. 64, 438-447 (1987).
162. Githure JI, Shatry AM, Tarara R et al. The suitability of East African primates as animal models of visceral leishmaniasis. Trans. R. Soc. Trop. Med Hyg. 80, 575-576 (1986).
163. Baba TW, Liska V, Hofmann-Lehmann R, et al. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat. Med. 6, 200-206 (2000).
164. Skeiky YA, Coler RN, Brannon M et al. Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial vaccine (Leish-111f) formulated in MPL adjuvant. Vaccine 10, 3292-3303 (2002).
165. Fries LF, Gordon DM, Richards RL et al. Liposomal malaria vaccine in humans: a safe and potent adjuvant strategy. Proc. Natl Acad. Sci. USA 89, 358-362 (1992).
166. Leroux-Roels G, Moreux E, Verhasselt B et al. Immunogenicity and reactogenicity of a recombinant HSV-2-glycoprotein D vaccine with or without monophosphoryl lipid A in HSV seronegative and seropositive subjects. 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, 341 (1993) (Abstract 1209).
167. Thoelen S, Van Damme P, Mathei C et al. Safety and immunogenicity of a hepatitis B vaccine formulated with a novel adjuvant system. Vaccine 16, 708-714 (1998).
168. Kawasaki K, Nishijima M. Molecular basis for innate immune recognition of microbial components. Jpn. J. Infect. Dis. 54, 220-224 (2001).
169. Vasselon T, Detmers PA. Toll receptors: a central element in innate immune responses. Infect. Immun. 70, 1033-1041 (2002).
170. Michie CA. Triage by Toll-like receptors. Trends Mol. Med. 8, 6 (2002).
171. Underhill DM, Ozinsky A. Toll-like receptors: key mediators of microbe detection. Curr. Opin. Immunol. 14, 103-110 (2002).
172. Persing DH, Coler RN, Lacy MJ, Johnson DA, Baldridge JR, Hershberg RM, Reed SG. Taking toll: lipid A mimetics as adjuvants and immunomodulators. Trends Microbiol. 10, S32-S37 (2002).
173. Agger EM, Andersen P. Tuberculosis subunit vaccine development: on the role of interferon-γ. Vaccine 19, 2298-2302 (2001).
174. Brandt L, Elhay M, Rosenkrands I, Lindblad EB, Andersen P. ESAT-6 subunit vaccination against Mycobacterium tuberculosis 2383. Infect. Immun. 68, 791-795 (2000).
175. Lindblad EB, Elhay MJ, Silva R, Appelberg R and Andersen P. Adjuvant modulation of immune responses to tuberculosis subunit vaccines. Infect. Immun. 65, 623-629 (1997).
176. Weinrich OA, van Pinxteren LA, Meng OL, Birk RP, Andersen P. Protection of mice with a tuberculosis subunit vaccine based on a fusion protein of antigen 85b and esat-6. Infect. Immun. 69, 2773-2778. (2001).
177. Coler RN, Bernards K, Greeson K et al. Immunization with a poly-protein vaccine consisting of the T cell antigens thiol-specific antioxidant, Leishmania major stress-inducible protein 1, and Leishmania elongation initiation factor protects against leishmaniasis. Infect. Immun. 70(8), 4215-4225 (2002).
178. Machado-Pinto JJ. Pinto CA, daCosta O et al. Immunochemotherapy for cutaneous leishmaniasis: a controlled trial using killed Leishmania (Leishmania) amazonensis vaccine plus antimonial. Int. J. Dermatol. 41, 73-78 (2002).