Evaluation of Alum-Naltrexone Adjuvant Activity, on Efficacy of Anti-Leishmania Immunization with Autoclaved Leishmania major (MRHO/IR/75/ER) Antigens in BALB/C Mice
Background: Naltrexone, an opioid receptor antagonist shifts the immune response toward a Th1 profile. In the current study, we evaluated the efficacy of the mixture of NTX and alum, as a new adjuvant, to enhance immune response and induce protection against Leishmania major in a mouse model.
Methods: BALB/c mice were immunized three times either autoclaved L.major promastigotes’ antigens alone or in combination with the adjuvant alum, naltrexone or the alum–naltrexone mixture. Both humoral and cellular immune responses were assessed two weeks after the last immunization and compared with control mice.
Results: The administration of alum- NTX in combination with the parasite antigen, significantly increased production of IFN-γ, IFN-γ /IL-5 ratio,lymphocyte proliferation and improved DTH response against L. major.There was no significant difference in survival following challenge among groups.
Conclusion: Immunization with the alum– naltrexone mixture as an adjuvant,in combination with the autoclaved L. major promastigotes antigens,can enhance cellular immunity and shift the immune responses to a Th1 pattern.
Reithinger R, Dujardin JL, Louzir H, Pirmez C, Alexander B, Brooker S. Cutaneous leishmaniasis.Lancet Infect Dis. 2007; 7(9):581–96.
2 .Badiee A, Jaafari RM, Khamesipour A. Leishmania major: Immune response in BALB/cmice immunized with stress-inducible protein 1 encapsulated in liposomes. Exp Parasitol. 2007; 115(2): 127–34.
3 .Nagill R, Kaur S. Vaccine candidates for leishmaniasis: A review. Int J Immunopharm. 2011; 11(10):1464-88.
Khamesipour A, Rafati S, Davoudi N, Maboudi F, Modabber F. Leishmaniasis vaccine candidates for development: a global overview. Indian J Med Res. 2006; 123 (3): 423–38.
5 .Nadim A, Javadian E, Tahvildar-Bidruni G, Ghorbani M. Effectiveness of leishmanization in the control of cutaneous leishmaniasis. Bull Soc Pathol Exot Filiales. 1983; 76 (4): 377–83.
Badiee A, HeraviShargh V, Khamesipour A, Jaafari MR. Micro/nanoparticle adjuvants for antileishmanial vaccines: Present and future trends. Vaccine. 2013; 31 (5):735–49.
Petrovsky N, Aguilar J. Vaccine adjuvants: Current state and future trends. Immunol Cell Biol. 2004; 82(5): 488–96.
Mohebali M, Khamesipour A, Mobedi I, Zabih Z, Hashemi-Fesharki R. Double-blind randomized efficacy field trial of alum 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, Javadian E. Hashemi- Fesharki R. Trial of non -living crude vaccine against zoonotic cutaneous leishmaniasis. Med J Islamic Republic Iran. 1995.8(4):211-15.
Momeni AZ, Jalayer T, Emamjomeh M et al. A randomised, double blind, controlled trial of a killed L. major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran. Vaccine. 1998; 17 (5):466–72.
Armijos RX, Weigel MM, Calvopina M, Hidalgo A, Cevallos W, Correa J. Immunogenecity, and efficacy of an autoclaved Leishmania amazonensis vaccine plus BCG adjuvant against New World cutaneous leishmaniasis. Vaccine. 2004; 22 (9-10):1320–6.
Sharifi I, Fekri AR, Aflatonian MR et al. Randomized vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran. Lancet.1998; 351(9115):1540-3.
Shoenfeld Y, Isenberg DA. Mycobacteria and autoimmunity. Immunol Today. 1988; 9(6):178–82
De Gregorio E, Tritto E, Rappuoli R. Alum adjuvanticity: unraveling a century old mystery. Eur J Immunol. 2008; 38(8): 2068- 71.
Harandi AM, Medaglini D, Shattock RJ. Vaccine adjuvants: a priority for vaccine research. Vaccine. 2010; 28(12): 2363-6.
Reed SG, Bertholet S, Coler RN, Friede M. New horizons in adjuvants for vaccine development. Trends Immunol. 2009; 30(1): 23-32.
Panerai AE, Sacerdote P. Beta-endorphin in the immune system: a role at last? Immunol Today. 1997; 18(7):317-9.
Sheridan JF, Dobbs C, Brown D, Zwilling B. Psychoneuroimmunology: Stress Effects on Pathogenesis and Immunity during Infection. Clin Microbiol Rev. 1994; 7(2): 200-12.
Donahue R, McLaughlin P, Zagon I. The opioid growth factor (OGF) and low dose naltrexone (LDN) suppress human ovarian cancer progression in mice. Gynecol Oncol. 2011; 122(2): 382–88.
Krupitsky E, Zvartau E, Blokhina E et al. Randomized trial of long-acting sustained-release Naltrexone implant vs. oral Naltrexone or placebo for preventing relapse to opioid dependence. Arch Gen Psychiatry. 2012; 69(9): 973-81.
Gekker G, Lokensgard JR, Peterson PK. Naltrexone potentiates anti-HIV-1 activity of antiretroviral drugs in CD4+ lymphocyte cultures. Drug Alcohol Depend. 2001; 64(3): 257-63.
Brown N, Panksepp J. Low-dose naltrexone for disease prevention and quality of life. Med Hypotheses. 2009;72(3): 333–37.
Ebrahimpour S, Tabari MA, Youssefi MR, Aghajanzadeh H, Behzadi MY. Synergistic effect of aged garlic extract and naltrexone on improving immune responses to experimentally induced fibrosarcoma tumor in BALB/c mice. Pharmacognosy Res. 2013; 5(3): 189-94.
Jazani NH, Sohrabpour M, Mazloomi E, Shahabi S. A novel adjuvant, a mixture ofalum and the general opioid antagonist naloxone, elicits both humoral and cellular immune responses for heat-killed Salmonella typhimurium vaccine. FEMS Immunol Med Microbiol. 2011; 61(1): 54-62.
Mazloomi E, Jazani NH, Shahabi S. A novel adjuvant, mixture of alum and the betaadrenergic receptor antagonist propranolol, elicits both humoral and cellular immune responses for heat-killed Salmonella typhimurium vaccine.Vaccine. 2012; 30(16): 2640-46.
Jazani NH, Karimzad M, Mazloomi E, Sohrabpour M, Hassan ZM, Ghasemnejad H, Roshan-Milani S, Shahabi S. Evaluation of the adjuvant activity of naloxone, an opioid receptor antagonist, in combination with heat-killed Listeria monocytogenes vaccine. Microbes Infect. 2010; 12(5): 382-8.
Jazani NH, Parsania S, Sohrabpour M, Mazloomi E, Karimzad M, Shahabi S. Naloxone and alum synergistically augment adjuvant activities of each other in a mouse vaccine model of Salmonella typhimurium infection. Immunobiology. 2011;216(6):744-51.
Jamali A, Mahdavi M, Hassan ZM, Sabahi F, Farsani MJ, Bamdad T, Soleimanjahi H, Motazakker M, Shahabi S. A novel adjuvant, the general opioid antagonist naloxone, elicits a robust cellular immune response for a DNA vaccine. Int Immunol. 2009;21(3):217-25.
van Rooijen N. Antigen processing and presentation in vivo: the microenvironment as a crucial factor. Immunol Today. 1990; 11(12): 436-9.
Nakahara T, Moroi Y, Uchi H, Furue M. Differential role of MAPK signaling in human dendritic cell maturation and Th1/Th2 engagement. J Dermatol Sci. 2006;42(1):1-11.
Donahue RN, McLaughlin PJ, Zagon IS. The opioid growth factor (OGF) and low dose naltrexone (LDN) suppress human ovarian cancer progression in mice. Gynecol Oncol. 2011; 122(2):382-8.
Brown N, Panksepp J. Low-dose naltrexone for disease prevention and quality of life. Med Hypotheses .2009; 72(3):333-7.
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