Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7274
Title: Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-II
Authors: Santos, Diego Moura
Carneiro, Marcia Weber
Moura, Tatiana Rodrigues de
Fukutani, Kiyoshi Ferreira
Clarêncio, Jorge
Soto, Manuel
Espuelas, Socorro
Brodskyn, Claudia Ida
Barral, Aldina Maria Prado
Barral Netto, Manoel
Oliveira, Camila Indiani de
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Universidad Autonoma de Madrid. Departamento de Biologia Molecular. Centro de Biología Molecular Severo Ochoa. Madrid, Espanha
Departamento de Farmacia y Tecnología Farmacéutica / Universidad de Navarra. Facultad de Farmacia. Instituto de Salud Tropical. Pamplona, Spain
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. Salvador, BA, Brasil
Abstract: 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. Conclusion: Our results encourage the pursuit of immunization strategies employing nanobased delivery systems for vaccine development against cutaneous leishmaniasis caused by L. braziliensis infection.
Keywords: Vaccine
Nanoparticle
Leishmania
Kinetoplastid membrane protein-11
Issue Date: 2012
Publisher: Dove Press
Citation: SANTOS, D. M. et al. Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-II. International Journal of Nanomedicine, v. 7, p. 2115-2127, 2012.
ISSN: 1176-9114
dx.doi.org/10.2147/IJN.S30093
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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