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Evaluation of Immune Response Against Leishmaniasis in Balb/C Mice Immunized With Cationic Dotap/Dope/Chol Liposomes Containing Soluble Leishmania Major Antigens Publisher



Hojatizade M1 ; Badiee A2 ; Khamesipour A3 ; Jaafari MR4
Authors
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Authors Affiliations
  1. 1. Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
  2. 2. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  3. 3. Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Source: Iranian Journal of Parasitology Published:2019


Abstract

Background: Whole killed Leishmania vaccine reached phase III clinical trials but failed to display significant efficacy in human mainly due to limited Th1 inducer adjuvant. Liposomes consisting of 1, 2-dioleoyl-3trimethylammonium-propane (DOTAP) bearing an inherent adjuvanticity and 1, 2-dioleoyl-L-α-glycero-3-phosphatidylethanolamine (DOPE) is well known to intensify the efficacy of positively charged liposomes. Methods: Soluble Leishmania major antigens (SLA) encapsulated in cationic liposomes using lipid film method in 2016). BALB/c mice were immunized subcutaneously (SC), three times in a 2-wk interval, with Lip (DOTAP)-SLA+, Lip (DOTAP/DOPE)-SLA+, Lip (DOTAP/DOPE/CHO)-SLA+, Lip (DOTAP/DOPE/CHO), Lip (DOPE/CHO), SLA or HEPES buffer. At week 2 after the last booster injection, immunized mice have challenged SC in the footpad with L. major parasites. To investigate the rate of protection and the type of immune response generated in mice, lesions development was assessed, IL-4 and IFN-γ levels with the ratio of IgG2a/IgG1 isotype were studied to describe the type of generated immune response. Results: Mice immunized with all liposomal form of SLA showed smaller footpad swelling and lower parasite burden in the spleen and footpad compared to the group of mice received buffer. However, these formulations did not show protection against leishmaniosis because of a generated mixed Th1/Th2 response in mice characterized by high production of IFN-γ and IL4 and a high titer of IgG1 and IgG2a antibody. Conclusion: Immunization with Lip (DOTAP/DOPE/CHO)-SLA+ was not an appropriate strategy to protect mice against leishmaniosis. © 2019, Tehran University of Medical Sciences (TUMS). All rights reserved.
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