title: Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-11.
abstract: BACKGROUND
  Vaccine development has been a priority in the fight against leishmaniases, which are vector-borne diseases caused by Leishmania protozoa. Among the different immunization strategies employed to date is inoculation of plasmid DNA coding for parasite antigens, which has a demonstrated ability to induce humoral and cellular immune responses. In this sense, inoculation of plasmid DNA encoding Leishmania kinetoplasmid membrane protein-11 (KMP-11) was able to confer protection against visceral leishmaniasis. However, recently the use of antigen delivery systems such as poly(lactic-co-glycolic acid) (PLGA) nanoparticles has also proven effective for eliciting protective immune responses.
  
  
  METHODS
  In the present work, we tested two immunization strategies with the goal of obtaining protection, in terms of lesion development and parasite load, against cutaneous leishmaniasis caused by L. braziliensis. One strategy involved immunization with plasmid DNA encoding L. infantum chagasi KMP-11. Alternatively, mice were primed with PLGA nanoparticles loaded with the recombinant plasmid DNA and boosted using PLGA nanoparticles loaded with recombinant KMP-11.
  
  
  RESULTS
  Both immunization strategies elicited detectable cellular immune responses with the presence of both proinflammatory and anti-inflammatory cytokines; mice receiving the recombinant PLGA nanoparticle formulations also demonstrated anti-KMP-11 IgG1 and IgG2a. Mice were then challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development was not inhibited following either immunization strategy. However, immunization with PLGA nanoparticles resulted in a more prominent reduction in parasite load at the infection site when compared with immunization using plasmid DNA alone. This effect was associated with a local increase in interferon-gamma and in tumor necrosis factor-alpha. Both immunization strategies also resulted in a lower parasite load in the draining lymph nodes, albeit not significantly.
  
  
  CONCLUSIONS
  Our results encourage the pursuit of immunization strategies employing nanobased delivery systems for vaccine development against cutaneous leishmaniasis caused by L. braziliensis infection.
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Santos
authors.forename: Marcia W
authors.initials: MW
authors.lastname: Carneiro
authors.forename: Tatiana R
authors.initials: TR
authors.lastname: de Moura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukutani
authors.forename: Jorge
authors.initials: J
authors.lastname: Clarencio
authors.forename: Manuel
authors.initials: M
authors.lastname: Soto
authors.forename: Socorro
authors.initials: S
authors.lastname: Espuelas
authors.forename: Claudia
authors.initials: C
authors.lastname: Brodskyn
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.forename: Camila I
authors.initials: CI
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D007111:Immunity, Cellular; D019344:Lactic Acid / Q000737:chemistry; D007892:Leishmania braziliensis / Q000235:genetics / Q000276:immunology; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid