Iranian Journal of Parasitology 2018. 13(1):11-23.

Immunoprophylactic Potential of a Cocktail of Three Low Mo-lecular Weight Antigens of Leishmania donovani along with Various Adjuvants Against Experimental Visceral leishmania-sis
Harpreet KAUR, Ankita THAKUR, Sukhbir KAUR

Abstract


Background: Currently, there is no vaccine available for any form of leishmaniasis for human use, including visceral leishmaniasis (VL). The treatment relies on drugs associated with severe toxic side effects and increased parasite drug resistance. At present, there is a strong need to develop and implement a successful vaccine against this disease. Therefore, we evaluated immunoprophylactic potential of a cocktail of low molecular weight antigens along with various adjuvants.

Methods: The three antigens (2015, Department of Zoology, Panjab University, Chandigarh), 31kDa, 36 kDa and 51 kDa of L. donovani were used in this study. Inbred BALB/c mice were immunized with 10 µg of cocktail antigens i.e. 31+36+51kDa alone and along with different adjuvants (ALD, saponin, and liposome). Mice were boosted twice at an interval of 2 wk and after last dose; mice were given challenge infection with 107 promastigotes. Mice have sacrificed15 d post immunization and on 30, 60, 90 post-challenge days for evaluation of different parameters.

Results: Immunized animals showed reduced parasite load, increased DTH responses and elevated levels of IgG2a antibody. The levels of Th1 cytokines were higher as compared to Th2 cytokines in immunized animals.

Conclusion: Best results were obtained with cocktail of 31+36+51+liposome and this combination conferred maximum protection.


Keywords


Cocktail antigens; Experimental visceral leishmaniasis; Adjuvants

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References


WHO (2015). Leishmaniasis fact sheet number 375. http://www.who.int/mediacentre/factsheets/fs375/en/.

Kedzierski L. Leishmaniasis Vaccine: Where are We Today? J Glob Infect Dis. 2010; 2(2):177-85.

Modabber F. First generation vaccine in clinical development: moving but what next? Curr Opin Anti-infect Inv Drug. 2000; 2: 35-39.

Paraguai de Souza E, Bernardo RR, Palat-nik M, Palatnik de Sousa CB. Vaccination of Balb/c mice against experimental vis-ceral leishmaniasis with the GP36 glyco-protein antigen of Leishmania donovani. Vac-cine.2001;19(23-24):3104-15.

Palatnik-de-Sousa CB, Gomes EM, Para-guai-de-Souza E, Palatnik M, Luz K, Boro-jevic R. Leishmania donovani: titration of anti-bodies to the fucose-mannose ligand as an aid in diagnosis and prognosis of visceral leishmaniasis. Trans R Soc Trop Med Hyg. 1995; 89(4):390-3.

Rolland-Burger L, Rolland X, Grieve CW, Monjour L. Immunoblot analysis of the humoral immune response to Leishmania donovani infantum polypeptides in human visceral leishmaniasis. J Clin Microbiol. 1991; 29(7):1429-35.

Mary C, Ange G, Dunan S, Lamouroux D, Quilici M. Characterization of a circulat-ing antigen involved in immune complexes in visceral leishmaniasis patients. Am J Trop Med Hyg. 1993;49(4):492-501.

Berrahal F, Mary C, Roze M et al. Canine leishmaniasis: identification of asympto-matic carriers by polymerase chain reaction and immunoblotting. Am J Trop Med Hyg. 1996; 55(3):273-7.

Oda K, Matsuda H, Murakami T et al. Ad-juvant and haemolytic activities of 47 sap-onins derived from medicinal and food plants. Biol Chem. 2000; 381(1):67-74.

Allison AG, Gregoriadis G. Liposomes as immunological adjuvants. Nature. 1974; 252(5480):252.

Nagill R, Kaur S. Enhanced efficacy and immunogenicity of 78 kDa antigen formu-lated in various adjuvants against murine visceral leishmaniasis. Vaccine. 2010; 28(23):4002-12.

Aguilar-Be I, da Silva Zardo R, Paraguai de Souza E et al. Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous mu-rine leishmaniasis. Infect Immun. 2005; 73(2):812-9.

Afrin F, Ali N. Adjuvanticity and protective immunity elicited by Leishmania donovani an-tigens encapsulated in positively charged liposomes. Infect Immun.1997; 65(6):2371-7.

Bradley DJ, Kirkley J. Regulation of Leish-mania population within host 1. The varia-ble course of L. donovani infections in mice. Clin Exp Immunol. 1977;30(1):119-29.

Kaur S, Kaur T, Garg N, Mukherjee S, Raina P, Athokpam V. Effect of dose and route of inoculation on the generation of CD4+ Th1/Th2 type of immune re-sponse in murine visceral leishmaniasis. Parasitol Res. 2008; 103(6):1413-9.

Ravindran R, Anam K, Bairagi BC et al. Characterization of immunoglobulin and its subclass response to Indian Kala Azar infection before and after chemotherapy. Infect Immun. 2004;72(2):863-70.

Bern C, Maguire JH, Alvar J. Complexities of assessing the disease burden attributa-ble to leishmaniasis. PLoS Negl Trop Dis. 2008; 2(10):e313.

Ravindran R, Ali N. Progress in vaccine research and possible effector mecha-nisms in visceral leishmaniasis. Curr Mol Med. 2004; 4(6):697-709.

Misra A, Dube A, Srivastava B et al. Suc-cessful vaccination against Leishmania do-novani infection in Indian langur using al-um-precipitated autoclaved Leishmania major with BCG. Vaccine. 2001; 19(25-26):3485-92.

Okwor I, Liu D, Beverley SM, Uzonna JE. Inoculation of killed Leishmania major into immune mice rapidly disrupts immunity to a secondary challenge via IL-10- mediated process. Proc Natl Acad Sci U S A. 2009; 106(33):13951-6.

Mohebali M, Khamesipour A, Mobedi I, Zarei Z, Hashemi-Fesharki R. Double-blind randomized efficacy field trial of al-um precipitated autoclaved Leishmania major vaccine mixed with BCG against canine visceral leishmaniasis in Meshkin-Shahr district, I.R. Iran. Vaccine. 2004;22(29-30):4097-100.

Mohebali M, Fallah E, Jamshidi Sh, Haj-jaran, H. Vaccine trial against canine viscer-al leishmaniasis in the Islamic Republic of Iran. East. Mediterr. Health J. 1998; 4: 234–238.

Marty P, Lelièvre A, Quaranta JF et al. De-tection by Western blot of four antigens characterizing acute clinical leishmaniasis due to Leishmania infantum. Trans R Soc Trop Med Hyg. 1995; 89(6):690-1.

Kamoun-Essghaier S, Guizani I, Strub JM et al. Proteomic approach for characteriza-tion of immunodominant membrane-associated 30- to 36-kilodalton fraction an-tigens of Leishmania infantum promastigotes, reacting with sera from mediterranean vis-ceral Leishmaniasis patients. Clin Diagn Lab Immunol. 2005; 12(2):310-20.

Reiner NE. Host-parasite relationship in murine leishmaniasis: pathophysiological and immunological changes. Infect Im-mun.1982; 38(3):1223-30.

Engwerda CR, Murphy ML, Cotterell SE, Smelt SC, Kaye PM. Neutralization of IL-12 demonstrates the existence of discrete organ-specific phases in the control of Leishmania donovani. Eur J Immunol. 1998; 28(2):669-80.

Bhowmick S, Ali N. Identification of novel Leishmania donovani antigens that help define correlates of vaccine-mediated protection in visceral leishmaniasis. PLoS One. 2009; 4(6):e5820.

Kaur J, Kaur T, Kaur S. Studies on the protective efficacy and immunogenicity of Hsp70 and Hsp83 based vaccine formula-tions in Leishmania donovani infected BALB/c mice. Acta Trop. 2011;119(1):50-6.

Bhowmick S, Ravindran R, Ali N. gp63 in stable cationic liposomes confers sustained vaccine immunity to susceptible BALB/c mice infected with Leishmania donovani. In-fect Immun. 2008; 76(3):1003-15.

Kumari S, Samant M, Misra P, Khare P, Sisodia B, Shasany AK, Dube A. Th1-stimulatory polyproteins of soluble Leish-mania donovani promastigotes ranging from 89.9 to 97.1 kDa offers long-lasting pro-tection against experimental visceral leish-maniasis. Vaccine. 2008; 26(45):5700-11.

Aguilar-Be I1, da Silva Zardo R, Paraguai de Souza E et al. Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous mu-rine leishmaniasis. Infect Immun. 2005; 73(2):812-9.

Carvalho EM, Johnson WD, Barreto E, Marsden PD, Costa JL, Reed S, Rocha H. Cell mediated immunity in American cuta-neous and mucosal leishmaniasis. J Im-munol. 1985; 135(6):4144-8.

El-On J. Current status and perspectives of the immunotherapy of leishmaniasis. Isr Med Assoc J. 2009; 11(10):623-8..

Kobayashi M, Fitz L, Ryan M et al. Identi-fication and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med. 1989; 170(3):827-45.

Das A, Ali N. Combining cationic liposo-mal delivery with MPL-TDM for cysteine protease cocktail vaccination against Leish-mania donovani: evidence for antigen synergy and protection. PLoS Negl Trop Dis. 2014; 8(8):e3091.

Jaafari MR, Badiee A, Khamesipour A et al. The role of CpG ODN in enhance-ment of immune response and protection in BALB/c mice immunized with recom-binant major surface glycoprotein of Leishmania (rgp63) encapsulated in cationic liposome. Vaccine. 2007; 25(32):6107-17.

Mazumdar T, Anam K, Ali N. A mixed Th1/Th2 response elicited by a liposomal formulation of Leishmania vaccine instructs Th1 responses and resistance to Leishmania donovani in susceptible BALB/c mice. Vac-cine. 2004; 22(9-10):1162-71.

Grenfell RF, Marques-da-Silva EA, Souza-Testasicca MC et al. Antigenic extracts of Leishmania braziliensis and Leishmania ama-zonensis associated with saponin partially protects BALB/c mice against Leishmania chagasi infection by suppressing IL-10 and IL-4 production. Mem Inst Oswaldo Cruz. 2010;105(6):818-22.

Heravi Shargh V, Jaafari MR, Khamesipour A et al. Cationic liposomes containing soluble Leishmania antigens (SLA) plus CpG ODNs induce protection against murine model of leishmaniasis. Parasitol Res. 2012; 111(1):105-14.


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