Induction of protection against leishmaniasis in susceptible BALB/c mice using simple DOTAP cationic nanoliposomes containing soluble Leishmania antigen (SLA)

Acta Trop. 2013 Dec;128(3):528-35. doi: 10.1016/j.actatropica.2013.07.021. Epub 2013 Aug 2.

Abstract

A suitable adjuvant and delivery system are needed to develop an effective vaccine against leishmaniasis. To induce a Th1 type of response and protection in BALB/c mice against Leishmania major infection, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) nanoliposomes bearing an intrinsic adjuvanticity, were used as an antigen delivery system and immunoadjuvant for soluble Leishmania antigens (SLA). DOTAP liposomes containing different concentrations of SLA were prepared by using lipid film method followed by sonication. The prepared vesicles showed a diameter of about 100nm, a positive zeta potential and approximately 70% encapsulation efficiency of SLA. BALB/c mice were immunized subcutaneously (SC), three times in a 3-week interval with different concentrations of liposomal SLA (12.5, 25, and 50μg of SLA/50μl/mice), free SLA and as well as free liposome. The group of mice received 50μg of SLA in DOTAP-nanoliposomes showed a significantly (p<0.001) smaller footpad swelling and the lowest spleen and footpad parasite burden after the challenge. This group also showed the highest IFN-γ production compared to the other groups, lower IL-4 level and higher IgG2a antibody titer. Taken together, the results indicated that simple DOTAP nanoliposome containing 1μg/μl SLA are appropriate delivery systems to induce a Th1 type of immune response and protection against L. major infection in BALB/c mice.

Keywords: Adjuvant; DOTAP; Leishmaniasis; Nanoliposomes; SLA; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antigens, Protozoan / administration & dosage
  • Antigens, Protozoan / immunology*
  • Disease Models, Animal
  • Fatty Acids, Monounsaturated / administration & dosage*
  • Female
  • Foot / parasitology
  • Injections, Subcutaneous
  • Leishmania major / immunology
  • Leishmania major / isolation & purification
  • Leishmaniasis / prevention & control*
  • Leishmaniasis Vaccines / administration & dosage
  • Leishmaniasis Vaccines / immunology*
  • Liposomes / administration & dosage*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage*
  • Parasite Load
  • Quaternary Ammonium Compounds / administration & dosage*
  • Vaccination / methods

Substances

  • Adjuvants, Immunologic
  • Antigens, Protozoan
  • Fatty Acids, Monounsaturated
  • Leishmaniasis Vaccines
  • Liposomes
  • Quaternary Ammonium Compounds
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane