Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Maritsa Margaroni,1,2 Maria Agallou,1 Evita Athanasiou,1 Olga Kammona,3 Costas Kiparissides,3,4 Catherine Gaitanaki,2 Evdokia Karagouni1 1Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 2Department of Animal and Human Physiology, School of Biology, Nationa...

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Autores principales: Margaroni M, Agallou M, Athanasiou E, Kammona O, Kiparissides C, Gaitanaki C, Karagouni E
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2017
Materias:
PLGA NPs
soluble Leishmania antigen
visceral leishmaniasis
vaccine
T cells
cytokines
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/b00d0dacdc704e70843050777f62da25
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spelling oai:doaj.org-article:b00d0dacdc704e70843050777f62da252021-12-02T05:03:11ZVaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis1178-2013https://doaj.org/article/b00d0dacdc704e70843050777f62da252017-08-01T00:00:00Zhttps://www.dovepress.com/vaccination-with-polydl-lactide-co-glycolide-nanoparticles-loaded-with-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Maritsa Margaroni,1,2 Maria Agallou,1 Evita Athanasiou,1 Olga Kammona,3 Costas Kiparissides,3,4 Catherine Gaitanaki,2 Evdokia Karagouni1 1Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 2Department of Animal and Human Physiology, School of Biology, National and Kapodistrian University of Athens, Athens, 3Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, 4Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, Greece Abstract: Visceral leishmaniasis (VL) persists as a major public health problem, and since the existing chemotherapy is far from satisfactory, development of an effective vaccine emerges as the most appropriate strategy for confronting VL. The development of an effective vaccine relies on the selection of the appropriate antigen and also the right adjuvant and/or delivery vehicle. In the present study, the protective efficacy of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface-modified with a TNFα-mimicking eight-amino-acid peptide (p8) and further functionalized by encapsulating soluble Leishmania infantum antigens (sLiAg) and monophosphoryl lipid A (MPLA), a TLR4 ligand, was evaluated against challenge with L. infantum parasites in BALB/c mice. Vaccination with these multifunctionalized PLGA nanoformulations conferred significant protection against parasite infection in vaccinated mice. In particular, vaccination with PLGA-sLiAg-MPLA or p8-PLGA-sLiAg NPs resulted in almost complete elimination of the parasite in the spleen for up to 4 months post-challenge. Parasite burden reduction was accompanied by antigen-specific humoral and cellular immune responses. Specifically, injection with PLGA-sLiAg-MPLA raised exclusively anti-sLiAg IgG1 antibodies post-vaccination, while in p8-PLGA-sLiAg-vaccinated mice, no antibody production was detected. However, 4 months post-challenge, in mice vaccinated with all the multifunctionalized NPs, antibody class switching towards IgG2a subtype was observed. The study of cellular immune responses revealed the increased proliferation capacity of spleen cells against sLiAg, consisting of IFNγ-producing CD4+ and CD8+ T cells. Importantly, the activation of CD8+ T cells was exclusively attributed to vaccination with PLGA NPs surface-modified with the p8 peptide. Moreover, characterization of cytokine production in vaccinated–infected mice revealed that protection was accompanied by significant increase of IFNγ and lower levels of IL-4 and IL-10 in protected mice when compared to control infected group. Conclusively, the above nanoformulations hold promise for future vaccination strategies against VL. Keywords: nanovaccine, soluble Leishmania antigen, visceral leishmaniasis, immune response, T cells, cytokines Margaroni MAgallou MAthanasiou EKammona OKiparissides CGaitanaki CKaragouni EDove Medical PressarticlePLGA NPssoluble Leishmania antigenvisceral leishmaniasisvaccineT cellscytokinesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 6169-6184 (2017)
institution DOAJ
collection DOAJ
language EN
topic PLGA NPs
soluble Leishmania antigen
visceral leishmaniasis
vaccine
T cells
cytokines
Medicine (General)
R5-920
spellingShingle PLGA NPs
soluble Leishmania antigen
visceral leishmaniasis
vaccine
T cells
cytokines
Medicine (General)
R5-920
Margaroni M
Agallou M
Athanasiou E
Kammona O
Kiparissides C
Gaitanaki C
Karagouni E
Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis
description Maritsa Margaroni,1,2 Maria Agallou,1 Evita Athanasiou,1 Olga Kammona,3 Costas Kiparissides,3,4 Catherine Gaitanaki,2 Evdokia Karagouni1 1Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 2Department of Animal and Human Physiology, School of Biology, National and Kapodistrian University of Athens, Athens, 3Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, 4Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, Greece Abstract: Visceral leishmaniasis (VL) persists as a major public health problem, and since the existing chemotherapy is far from satisfactory, development of an effective vaccine emerges as the most appropriate strategy for confronting VL. The development of an effective vaccine relies on the selection of the appropriate antigen and also the right adjuvant and/or delivery vehicle. In the present study, the protective efficacy of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface-modified with a TNFα-mimicking eight-amino-acid peptide (p8) and further functionalized by encapsulating soluble Leishmania infantum antigens (sLiAg) and monophosphoryl lipid A (MPLA), a TLR4 ligand, was evaluated against challenge with L. infantum parasites in BALB/c mice. Vaccination with these multifunctionalized PLGA nanoformulations conferred significant protection against parasite infection in vaccinated mice. In particular, vaccination with PLGA-sLiAg-MPLA or p8-PLGA-sLiAg NPs resulted in almost complete elimination of the parasite in the spleen for up to 4 months post-challenge. Parasite burden reduction was accompanied by antigen-specific humoral and cellular immune responses. Specifically, injection with PLGA-sLiAg-MPLA raised exclusively anti-sLiAg IgG1 antibodies post-vaccination, while in p8-PLGA-sLiAg-vaccinated mice, no antibody production was detected. However, 4 months post-challenge, in mice vaccinated with all the multifunctionalized NPs, antibody class switching towards IgG2a subtype was observed. The study of cellular immune responses revealed the increased proliferation capacity of spleen cells against sLiAg, consisting of IFNγ-producing CD4+ and CD8+ T cells. Importantly, the activation of CD8+ T cells was exclusively attributed to vaccination with PLGA NPs surface-modified with the p8 peptide. Moreover, characterization of cytokine production in vaccinated–infected mice revealed that protection was accompanied by significant increase of IFNγ and lower levels of IL-4 and IL-10 in protected mice when compared to control infected group. Conclusively, the above nanoformulations hold promise for future vaccination strategies against VL. Keywords: nanovaccine, soluble Leishmania antigen, visceral leishmaniasis, immune response, T cells, cytokines 
format article
author Margaroni M
Agallou M
Athanasiou E
Kammona O
Kiparissides C
Gaitanaki C
Karagouni E
author_facet Margaroni M
Agallou M
Athanasiou E
Kammona O
Kiparissides C
Gaitanaki C
Karagouni E
author_sort Margaroni M
title Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis
title_short Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis
title_full Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis
title_fullStr Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis
title_full_unstemmed Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis
title_sort vaccination with poly(d,l-lactide-co-glycolide) nanoparticles loaded with soluble leishmania antigens and modified with a tnfα-mimicking peptide or monophosphoryl lipid a confers protection against experimental visceral leishmaniasis
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/b00d0dacdc704e70843050777f62da25
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